10-(3-cyclopropylaminomethyl-1-pyrrolidinyl)pyridobenzoxazinecarboxylic acid derivative effective against resistant bacterium

10-(3-Cyclopropylaminomethyl-l-pyrrolidinyl)pyridobenzoxazine carboxylic acid derivatives effective against drug-resistant bacteria TECHNICAL FIELD The present invention relates to novel 10-(3cyclopropylaminomethyl-l-pyrrolidinyl)pyridobenzoxazine carboxylic acid derivatives, salts and hydrates thereof that, in addition to being safe and exhibiting strong antibacterial activities, are effective against drug-resistant bacteria that are less susceptible to conventional antibacterial agents. TECHNICAL BACKGROUND Reference should be made to the following articles: Japanese Patent Laid-Open Publication No. Sho 57-4698 (Patent Article i); Japanese Patent Laid-Open Publication No. Sho 61204188 (Patent Article 2); Japanese Patent Laid-Open Publication No. Sho 62-155282 (Patent Article 3). Since the development of norfloxacin, considerable effort has been made worldwide to develop quinolone carboxylic acidbased antibacterial agents, which are also known as new quinolones and have now become important cures for infectious diseases. The recent emergence of drug-resistant bacteria, such as Methicillin-Resistant Staphylococcus aureus (MRSA), Penicillin-Resistant Streptococcus pneumoniae (PRSP), and Vancomycin-Resistant Enterococcus (VRE), most of which are gram-positive bacteria, has posed a serious threat to the treatment of patients. Traditional quinolone carboxylic acid-based antibacterial agents have relatively weak antibacterial activities against gram-positive bacteria and thus are not considered as effective cures for the drugresistant bacteria. Furthermore, the increasing incidence of Quinolone-Resistant Staphylococcus aureus (QRSA) makes the use of these drugs even more difficult. While pyridobenzoxazine carboxylic acid-based antibacterial agents similar to the ones claimed in the present invention are described in, for example, Patent Articles I, 2, and 3, none of these agents offer sufficient antibacterial activity against gram-positive bacteria, nor are they described to have antibacterial activity against drug-resistant bacteria such as those described above. DISCLOSURE OF THE INVENTION The present invention relates to novel pyridobenzoxazine carboxylic acid-based compounds that, in addition to being safe and exhibiting strong antibacterial activities, are effective against drug-resistant bacteria that are less susceptible to conventional antibacterial agents. N: \Melbourne\Cases\Patent000-54999\P54194 .AU\Specis\P54194 .AU Specification 2008-8-4 .doc In view of the above-described problems, the present inventors have devoted a significant amount of effort to seeking quinolone carboxylic acid derivatives that are effective against gram-positive bacteria, in particular, such drug-resistant bacteria as MRSA, PRSP, and VRE, which are less susceptible to traditional quinolone carboxylic acidbased antibacterial agents. The effort was rewarded by the discovery of the compounds of the present invention, which proved to be effective against gram-positive bacteria, in particular, such drug-resistant bacteria as MRSA, PRSP, and VRE 0 and exhibit higher antibacterial activity as compared not only with traditional quinolone carboxylic acid-based antibacterial agents, but also with various other antibacterial agents. The discovery ultimately led the present inventors to complete the present invention. According to the present invention, there is provided a compound as represented by the following general formula (I), or a salt or a hydrate thereof: N -RI N:\Me)bourne\Case$\Patent000-54999\P54194.AU\Specis\P54194.AU Specification 2008-8-4.doc wherein R1 is a fluoromethyl group; R2 is a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms, or a pharmaceutically acceptable cation and an ester of a prodrug; R3 is a hydrogen atom or a halogen atom; R4 is a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms, a fluoromethyl group, a trifluoromethyl group or a fluorine atom; and R5 is a hydrogen atom or a fluorine atom. Examples of the lower alkyl group in the general formula (I) include a methyl group, an ethyl group, a propyl group, an isopropyl group, and a cyclopropyl group. Examples of the pharmaceutically acceptable cation include sodium ion, potassium ion, magnesium ion, calcium ion, and ammonium ion. Examples of the ester of a prodrug include a pivaloyloxymethyl group, an acetoxymethyl group, a phthalidinyl group, an indanyl group, a methoxymethyl group, and a 5-methyl-2-oxo-l,3-dioxolene-4-yl group. Examples of the halogen atom include fluorine, chlorine, bromine, and iodine. Further according to the present invention there is provided an antibacterial agent containing as an active ingredient the compound as described above, a salt or a hydrate thereof. The present invention also provides a pharmaceutical composition comprising the compound as described above, a salt or a hydrate thereof and a pharmaceutically acceptable carrier. N:\Me]bourne\Cases\Patent000-54999\P54194.AU\Specis\P54194.AU Specification 2008-8-4.d0c The present invention further provides a method of treating a bacterial infection comprising administering an effective amount of the compound as described above, a salt or a hydrate thereof to a subject in need thereof. The present invention still further provides a use of the compound as described above, a salt or a hydrate thereof in the manufacture of a medicament for treating a bacterial infection. The present invention even further provides use of the compound as described above, a salt or a hydrate thereof for treating a bacterial infection. BEST MODE FOR CARRYING OUT THE INVENTION An exemplary production process of the compound of the present invention will now be described. The compound of the present invention may be produced by reacting a compound represented by the following general 4a N:\Me]bourne\Cases\Patent000-54999\P54194.AU\Specls\P54194.AU Specification 2008-8-4.doc formula (II): R3\ H o-..RI [wherein R1 and R3 are the same as in the general formula (I); and R6 is represented by the following general formula (III): B,R 8 I [wherein R6 and R7 are each independently a fluorine atom, or a lower alkylcarbonyloxy group]] with a compound represented by the following general formula (IV), or an acid addition salt thereof: RIO NH IV [wherein R4 and R5 are the same as in the general formula (I); and RI0 is a hydrogen atom or a protective group of nitrogen atom such as t-butoxycarbonyl] and then removing the boron chelate and, if necessary, the protective group of nitrogen atom. The reaction of the compound of the general formula (II) with the compound of the general formula (IV) may be carried out in the absence or presence of a solvent, such as an alcohol, acetonitrile, dimethylsulfoxide, N,Ndimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, tetrahydrofuran, dioxane, benzene, or toluene, and in the presence of an acid receptor. The acid receptor may be a carbonate or a hydrogen carbonate of an alkali metal or an alkaline earth metal, or a basic organic compound, such as triethylamine, diazabicyclo-7-undecene, or pyridine. The reaction is typically carried out at a temperature in the range of room temperature to 200°C and preferably in the range of 25°C to 150°C. The reaction takes from 30min to 48 hours and is typically complete within 30min to 15 hours. If desired, the compound of the general formula (I) may be converted to its salt using an ordinary technique. Examples of such salts include salts formed with an inorganic acid, such as hydrochloric acid, sulfuric acid, and phosphoric acid, salts formed with an organic acid, such as methanesulfonic acid, lactic acid, oxalic acid, and acetic acid, and salts formed with sodium, potassium, magnesium, calcium, aluminum, cerium, chromium, cobalt, copper, iron, zinc, platinum, silver, or the like. The compound of the present invention may be administered to humans or animals in a pharmaceutically known form through a pharmaceutically known route. For example, the compound may be prepared in the form of powders, tablets, capsules, ointments, injections, syrups, solutions, eye drops, and suppositories for oral or parenteral administration. EXAMPLES Exemplary tests as well as production processes for the compound of the present invention will now be described in detail with reference to examples. Reference Example 1 Bis(acetato-O) [(3R)-9,10-difluoro-3-fluoromethyl-2,3-dihydro7-oxo-7H-pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylatoO6,OT]boron To a mixture of boric acid (12.8g) and acetic anhydride (63.4g), zinc chloride (236mg) was added and the resulting mixture was stirred at room temperature for 0.5 hours. To this mixture, (3R)-9,10-difluoro-3-fluoromethyl-2,3-dihydro-7-oxo7H-pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid ethyl ester (22.6g) was added and the mixture was stirred at 60°C for 2.5 hours. Subsequently, the reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate (300mL). The solution was sequentially washed with a saturated aqueous solution of sodium hydrogen carbonate (2 x 200mL) and then with water (100mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (dichloromethane: acetone = 7:1), and the eluted yellow amorphous product was crystallized in an acetone/diethyl ether mixture to give 24.5g of bis (acetato-O) [ (3R)-9, 10-difluoro-3-fluoromethyl-2,3dihydro-7-oxo-7H-pyrido[l, 2,3-d, e] [I, 4 ] benzoxazine-6carboxylato-O6,O7]boron as a white powder. IH NMR(CDCI 3 ): 6 1.85 (s, 3H), 2.05 (s, 3H), 4.62 (ddd, J = Hz, 3.9 Hz, 12.2 Hz, IH), 4.74 (ddd, J = 7.8 Hz, 10.3 Hz, 46.4 Hz, IH), 4.90 (ddd, J = 4.9 Hz, I0.3 Hz, 45.4 Hz, IH), 4.92 (dd, J = 1.0 Hz, 12.7 Hz, IH), 5.35-5.38 (m, IH), 7.92 (dd, = 7.3 Hz, 9.3 Hz, IH), 9.22 (s, IH). Elementary analysis (%) : Calcd for C 17 HI 3 BF 3 NOs"0.75H 2 0: C 46.34, H 3.32, N 3.18; found: C 46.30, H 3.34, N 3.30. Reference Example 2 Synthesis of bis(acetato-O) [ (3S)-9,10-difluoro-2,3-dihydro,3methoxymethyl-7-oxo-7H-pyrido [I, 2, 3-d, e] [I, 4 ] benzoxazine-6carboxylato-O 6, O 7] boron Step I: (3S)-9,10-Difluoro-2,3-dihydro-3-hydroxymethyl-7-oxo-7H- pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid ethyl ester (l.30g) was suspended in anhydrous dimethylformamide (40mL). Silver oxide (I) (4.63g) and methyl iodide (l.25mL) were then added to the suspension. The resulting mixture was stirred at room temperature for 21 hours. Subsequently, insoluble materials were removed from the reaction mixture filtration and the filtrate was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (dichloromethane: acetone= 5: I) to give 740mg of (3S)- 9,10-difluoro-2,3-dihydro-3-methoxymethyl-7-oxo-7Hpyrido [l, 2, 3-d, e] [l,4]benzoxazine-6-carboxylic acid ethyl ester as a white powder. MS (EI)m/z: 339 (M+) . Elementary analysis (%): Calcd for C 16 HIsF 2 NO 5 : C 56.64, H 4.46, N 4.13; found: C 56.56, H 4.71, N 4.26. Step 2 : In a similar manner to Reference Example I, (3S)-9,10difluoro-2,3-dihydro-3-methoxymethyl-7-oxo-7H-pyrido [ 1,2,3d,e] [l,4]benzoxazine-6-carboxylic acid ethyl ester (679mg) was reacted to give 830mg of bis(acetato-O)[ (3S)-9,10-difluoro2,3-dihydro-3-methoxymethyl-7-oxo-7H-pyrido [ 1,2,3d,e] [l,4]benzoxazine-6-carboxylato-O 6,O 7]boron as a colorless amorphous product. IH NMR(CDCI 3 ):6 1.86 (s, 3H), 2.06 (s, 3H), 3.39 (s, 3H), 3.70 (dd, J= 8.3 Hz, 10.3 Hz, IH), 3.82 (dd, J = 5.4 Hz, 10.3 Hz, IH), 4.56 (dd, J= 2.9 Hz, 12.2 Hz, IH), 4.86 (dd, J = 1.0 Hz, 12.2 Hz, IH), 5.10-5.13 (m, IH), 7.89 (dd, J = 7.3 Hz, 9.3 Hz, IH), 9.13 (s, IH). Elementary analysis (%): Calcd for C 18 HI 6 BF 2 NO 9 "I.5H 2 0: C 46.38, Reference Example 3 Synthesis of bis(acetato-O) [(3S)-3-acetoxymethyl-9,10difluoro-2,3-dihydro-7-oxo-7H-pyrido[l,2,3d,e] [l,4]benzoxazine-6-carboxylato-O6,07]boron Step I: (3S)-9,10-Difluoro-2,3-dihydro-3-hydroxymethyl-7-oxo-7Hpyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid ethyl ester (976mg) was suspended in anhydrous dichloromethane (30mL). To the suspension, acetic anhydride (368mg) and 4dimethylaminopyridine (5.0mg) were added and the resulting mixture was refluxed for 1.5 hours while heated. Subsequently, the mixture was allowed to cool and was washed with water. This was followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was suspended in ethanol and the suspension was filtrated to give 1.04g of (3R)-3-acetoxymethyl-9,10-difluoro-2,3-dihydro7-oxo-7H-pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid ethyl ester as a white powder. MS(EI)m/z: 367(M+) . Elementary analysis (%): Calcd for C 17 HIsF 2 NO 6 : C 55.59, H 4.12, N 3.81; found: C 56.25, H 4.15, N 3.93. Step 2: In a similar manner to Reference Example i,(3S) -3acetoxymethyl-9, 10-difluoro-2,3-dihydro-7-oxo-7H-pyrido [ 1,2,3 d,e] [l,4]benzoxazine-6-carboxylic acid ethyl ester (918mg) was reacted to give 1.00g of bis(acetato-O)[(3S)-3-acetoxymethyl9, 10-difluoro-2,3-dihydro-7-oxo-7H-pyrido [i, 2, 3d,e] [l,4]benzoxazine-6-carboxylato-O 6,O 7]boron as a colorless amorphous product. IH NMR(CDCI 3 ): 6 1.83 (s, 3H), 2.03 (s, 3H), 2.08 (s, 3H), 4.44-4.54 (m, 2H), 4.63 (dd, J = 2.9 Hz, 12.2 Hz, IH), 4.89 (dd, J = 1.0 Hz, 12.7 Hz, IH), 5.27-5.30 (m, IH), 7.88 (dd, J = 7.3 Hz, 9.3 Hz, IH), 9.17 (s, IH). Elementary analysis (%) : Calcd for C 19 HI 6 BF 2 NOI 0 "I.75H 2 0: C 45.76, H 3.94, N 2.81; found: C 45.94, H 3.82, N 2.95. Reference Example 4 Synthesis of trans-3-cyclopropylaminomethyl-4methylpyrrolidine Step i: trans-l-Benzyl-4-methyl-3-pyrrolidinecarboxylic acid (4.04g) was dissolved in dichloromethane (50mL). To this solution, l,l'-carbonylbis-IH-imidazole (3.58g) was added and the mixture was stirred at room temperature for 1 hour. While the reaction mixture was cooled on an ice bath, a dichloromethane solution (15mL) of cyclopropylamine (l.53mL) was added dropwise and the mixture was stirred at room temperature for 3 hours. Subsequently, the reaction mixture was washed with water, was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was crystallized in a hexane/diisopropyl ether mixture and the formed crystal was filtrated. The collected crystal was then washed with a hexane/diisopropyl ether mixture and was dried under reduced pressure to obtain 4.07g of trans-l-benzyl-N-cyclopropyl-4-methyl-3pyrrolidinecarboxamide as a white crystal. Melting point: 81-83°C. MS (EI) m/z: 258(M÷). Step 2: trans-l-Benzyl-N-cyclopropyl-4-methyl-3pyrrolidinecarboxamide (3.80g) was suspended in anhydrous tetrahydrofuran (85mL). To this suspension, a imol/L tetrahydrofuran solution of borane-tetrahydrofuran complex (58.8mL) was added and the mixture was refluxed for 8 hours while heated. Subsequently, a 2mol/L aqueous solution of sodium hydroxide (35mL) was added to the reaction mixture and the mixture was refluxed for 4 hours while heated. After concentration under reduced pressure, the resultant residue was extracted with toluene (2 x 100mL) and the toluene extracts were combined. The combined extract was washed with water, was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (50mL). To this solution, ditert-butyl dicarbonate (3.53g) was added and the mixture was stirred at room temperature for 4 hours. Subsequently, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified on a silica gel column (hexane: ethyl acetate = 4:1 shifted to I:I) to obtain 3.07g of trans-l-benzyl-3-[[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl]-4-methylpyrrolidine as a colorless oil. MS (FAB÷)m/z: 345 (MH÷). HRMS (FAB+): Calcd for C 21 H 33 N 2 0 2 (MH+): 345.2542; found: 345.2505. Step 3: trans-l-Benzyl-3-[[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl]-4-methylpyrrolidine (3.00g) was dissolved in ethanol (50mL). To this solution, 7.5% palladium carbon (300mg) was added and the mixture was stirred at room temperature for 6 hours under a hydrogen pressure of 3.9 x 10Spa. Subsequently, the catalyst was removed from the reaction mixture by filtration and the collected catalyst was washed with ethanol. The filtrate and the washing solution were combined and the resulting residue was dried under reduced pressure to obtain 2.12g of trans-3-[[(N-tertbutoxycarbonyl-N-cyclopropyl)amino]methyl]-4-methylpyrrolidine as a pale brown oil. MS (FAB÷) m/z: 255 (MH+). HRMS (FAB+): Calcd for C 14 H 27 N 2 0 2 (MH+): 255.2073; found: 255.2079. Step 4: trans-3-[[(N-tert-Butoxycarbonyl-Ncyclopropyl)amino]methyl]-4-methylpyrrolidine (2.07g) was dissolved in dichloromethane (10mL). While this solution was cooled on an ice bath, trifluoroacetic acid (5mL) was added and the mixture was stirred at room temperature for 2 hours. After concentration under reduced pressure, the resulting residue was dissolved in tetrahydrofuran (6mL) and the solution was allowed to stand for 13 hours at room temperature. The separated crystal was collected by filtration, followed by washing with tetrahydrofuran and drying under reduced pressure, to give 2.47g of trans-3-cyclopropylaminomethyl-4methylpyrrolidine trifluoroacetic acid salt. The salt product (2.37g) was dissolved in water (5mL), followed by addition of a 20% aqueous solution of sodium hydroxide to adjust the pH to 14. The solution was then extracted with diethyl ether (2 x 50mL) and the extracts were combined. The combined extract was then dried over anhydrous sodium sulfate and was concentrated under reduced pressure. The resulting residue was purified by distillation under reduced pressure to obtain 660mg of trans3-cyclopropylaminomet hyl4 -methylpyrrolidine. IH NMR(CDCI 3 ): 6 0.30-0.37 (m, 2H), 0.41-0.45(m, 2H), 1.04(d, J = 6.3 Hz, 3H), 1.66-1.76(m, 4H), 2.08-2.13(m, IH), 2.46(dd, J =7.3 Hz, 10.7 Hz, IH), 2.57(dd, J = 8.3 Hz, 11.7 Hz, IH), 2.63(dd, J =6.3 Hz, 10.7 Hz, IH), 2.80 (dd, J = 5.4 Hz, 11.7 Hz, IH), 3.10 (dd, J =6.8 Hz, 10.7Hz, IH), 3.14 (dd, J = 7.3 Hz, I0.7 Hz, IH). Elementary analysis (%): Calcd for C 9 HIBN 2 "2CF 3 COOH: C 40.84, H 5.27, N 7.33; found: C 40.90, H 5.47, N 7.37. Reference Example Synthesis of (3R,4R)-3-cyclopropylaminomethyl-4methylpyrrolidine Step i: (3R,4R)-l-Benzyl-4-methyl-3-pyrrolidinecarboxylic acid (6.27g) was suspended in dichloromethane (250mL). To this suspension, cyclopropylamine (l.76mL) and hydrochloric acid lethyl-(3-dimethylaminopropyl)carbodiimide (12.2g) were sequentially added and the mixture was stirred at room temperature for 4 hours. Subsequently, the reaction mixture was washed with water, was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (ethyl acetate: methanol = i0:I) to give 3.32g of (3R,4R)-l-benzyl-Ncyclopropyl-4-methyl-3-pyrrolidinecarboxamide as a white crystal. MS (EI) m/z: 258 (M+). Elementary analysis (%): Calcd for C 16 H 22 N 2 0: C 74.38, H 8.58, N 10.84; found: C 74.46, H 8.67, N 10.72. Step 2: In a similar manner to Step 2 in Reference Example 4, (3R, 4R)-l-benzyl-N-cyclopropyl-4-methyl-3pyrrolidinecarboxamide (5.52g) was reacted to give 4.16g of (3R,4R)-l-benzyl-3-[[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl]-4-methylpyrrolidine as a pale brown oil. MS (FAB+) m/z: 345 (MH+). HRMS (FAB+): Calcd for C 21 H 33 N 2 0 2 (MH+): 345.2542; found 345.2585. Step 3: In a similar manner to Step 3 in Reference Example 4, (3R,4R)-l-benzyl-3-[[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl]-4-methylpyrrolidine (4.00g) was reacted to give 2.88g of (3R, 4R)-3-[[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl]-4-methylpyrrolidine. MS (FAB+) m/z: 255 (MH+). HRMS (FAB+): Calcd for C 14 H 27 N 2 0 2 (MH+): 255.2073; found: 255.2070. Step 4: In a similar manner to Step 4 in Reference Example 4, (3R, 4R) -3- [ [ (N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl]-4-methylpyrrolidine (2.78g) was reacted to give 730mg of (3R,4R)-3-cyclopropylaminomethyl-4methylpyrrolidine. Specific rotation: +74.6°(c=0.648, methanol) . Elementary analysis (%): Calcd for C 9 HIBN 2 "2CF 3 COOH: C 40.84, 5.27, N 7.33; found: C 40.73, H 5.26, N 7.36. Reference Example 6 Synthesis of (3S,4S)-3-cyclopropylaminomethyl-4methylpyrrolidine Step i: In a manner similar to Step 1 in Reference Example 5, (3S,4S)-l-benzyl-4-methyl-3-pyrrolidinecarboxylic acid (14.5g) was reacted to give 6.33g of (3S,4S)-l-benzyl-N-cyclopropyl-4methyl-3-pyrrolidinecarboxamide as a pale brown crystal. MS (EI) m/z: 258 (M+). Elementary analysis (%): Calcd for C 16 H 22 N 2 0: C 74.38, H 8.58, 10.84; found: C 74.64, H 8.66, N 10.71. Step 2: In a manner similar to Step 2 in Reference Example 4, (3S,4S)-l-benzyl-N-cyclopropyl-4-methyl-3pyrrolidinecarboxamide (6.13g) was reacted to give 4.67g of (3S,4S)-l-benzyl-3-[[(N-tert-butoxycarbonyl-Ncycl0propyl)amino]methyl]-4-methylpyrrolidine as a pale brown oil. MS (FAB÷) m/z: 345 (MH+). HRMS (FAB÷): Calcd for C 21 H 33 N 2 0 2 (MH+): 345.2542; found: 345.2547. Step 3: In a similar manner to Step 3 in Reference Example 4, (3S,4S)-l-benzyl-3-[[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl]-4-methylpyrrolidine (4.47g) was reacted to give 3.05g of (3S,4S)-3-[[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl]-4-methylpyrrolidine. MS (FAB÷) m/z: 255 (MH+). HRMS (FAB+): Calcd for C 14 H 27 N 2 0 2 (MH÷): 255.2073; found 255.2075. Step 4: In a similar manner to Step 4 in Reference Example 4, (3S,4S)-3-[[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl]-4-methylpyrrolidine (2.85g) was reacted to give 1.21g of (3S,4S)-3-cyclopropylaminomethyl-4methylpyrrolidine. Specific rotation: -74.5°(c=0.62, methanol). Elementary analysis (%): Calcd for C 9 HI 8 N 2 "2CF 3 COOH: C 40.84, H Reference Example 7 Synthesis of cis-3-cyclopropylaminomethyi-4-methylpyrrolidine Step l: c is-l-Benzyl-3-hydroxy-4-methylpyrrolidine (6.81g) was dissolved in dichloromethane (70mL). While this solution was cooled on a dry ice/acetone bath, triethylamine (5.21mL) was added. Methanesulfonyl chloride (2.89mL) was then added dropwise and the mixture was further stirred for 1 hour. Following addition of water (50mL), the temperature of the mixture was allowed to rise to room temperature and the dichloromethane layer was separated. The aqueous layer was extracted with dichloromethane (50mL) and the extract was combined with the dichloromethane layer. The combined dichloromethane layer was then washed with water, followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was dissolved in acetonitrile (180mL). To this solution, tetrabutylammonium cyanide (23.9g) was added and the mixture was refluxed for 7 hours while heated. Subsequently, the reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate (300mL). The solution was washed with water, was dried over anhydrous sodium sulfate, and was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (hexane: ethyl acetate = i:I) to give 4.61g of cis-l-benzyl-4-methyl-3pyrrolidinecarbonitrile as a brown oil. IR (neat): 2240, 1496, 1454 cm-I. MS (EI) m/z: 200 (M÷). Step 2: Lithium aluminum hydride (80%, 3.89g) was suspended in diethyl ether (90mL). While the suspension was cooled on an ice bath, a diethyl ether solution (25mL) of cis-l-benzyl-4methyl-3-pyrrolidinecarbonitrile (4.11g) was added dropwise and the mixture was stirred at room temperature for 1 hour. While the reaction mixture was cooled on an ice bath, a saturated aqueous solution of sodium hydrogen carbonate (8mL) was carefully added dropwise. Following dilution with diethyl ether (100mL), insoluble materials were collected by filtration and were washed with diethyl ether. The filtrate and the washing solution were combined and the combined solution was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (hexane: ethyl acetate = I:i shifted to ethyl acetate: methanol = I0:i) to give 2.35g of cis-l-benzyl-4-methyl-3aminomethylpyrrolidine as a pale yellow oil. IH NMR(CDCI 3 ): 6 0.94 (d, J = 7.3 Hz, 3H), 1.09-1.66 (br, 2H), Step 3: c is-l-Benzyl-4-methyl-3-aminomethylpyrrolidine (1000mg) was dissolved in methanol (10mL). While this solution was cooled on an ice bath, benzaldehyde (0.50mL) was added dropwise and the mixture was stirred at room temperature for 1 hour. Subsequently, sodium cyanoborohydride (184mg) was added and the mixture was stirred at room temperature for 1.5 hours. This was followed by a second addition of sodium cyanoborohydride (123mg) and stirring for additional 5.5 hours. Subsequently, a 2mol/L aqueous solution of sodium hydroxide (5mL) was added to the reaction mixture and the mixture was refluxed for 2 hours while heated. Following concentration under reduced pressure, the resulting residue was extracted with toluene (2 x 30mL) and the toluene extracts were combined. The combined toluene layer was then washed with water, followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (hexane: ethyl acetate = 4:1) to give 690mg of cis-l-benzyl-3-benzylaminomethyl-4methylpyrrolidine as a pale yellow oil. MS (EI) m/z: 294 (M÷). HRMS (EI): Calcd for C 20 H 26 N 2 (M÷): 294.2096; found: 294.2110. Step 4: c is-l-Benzyl -3-benzylaminomethyl-4-methylpyrrolidine (680mg) was dissolved in methanol (7mL To this solution, molecular sieves 3A (700mg), acetic acid (l.32mL), [l- (ethoxycyclopropyl)oxy]trimethylsilane (l.85mL), and sodium cyanoborohydride (435mg) were added and the mixture was refluxed for 4 hours while heated. Insoluble materials were collected by filtration and were washed with methanol. The filtrate and the washing solution were combined and the combined organic layer was concentrated under reduced pressure. To the resulting residue, water was added (5mL), followed by addition of a 2mol/L aqueous solution of sodium hydroxide to make the mixture basic. The mixture was then extracted with toluene (2 x 50mL) and the extracts were combined. The combined toluene layer was then washed with water, was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (hexane: ethyl acetate = 4:1) to give 648mg of cis-l-benzyl-3-(N-benzyl-N-cyclopropyl)aminomethyl-4methylpyrrolidine as a colorless oil. MS (EI) m/z: 334 (M÷). HRMS (EI): Calcd for C 23 H 30 N 2 (M+) : 334.2409; found: 334.2403. Step 5: c is-l-Benzyl-3-(N-benzyl-N-cyclopropyl)aminomethyl-4methylpyrrolidine (640mg) was dissolved in ethanol (10mL). To this solution, 10% palladium carbon (500mg) and chloroform (0.77mL) were added and the mixture was stirred at 50°C for 7 hours under a hydrogen pressure of 3.9 x 105pa. From the reaction mixture, the catalyst was collected by filtration and was washed with ethanol. The filtrate and the washing solution were combined and the combined organic layer was concentrated under reduced pressure. To the resulting residue, water (2mL) was added, followed by addition of a 2mol/L aqueous solution of sodium hydroxide to make the mixture basic. Sodium chloride was then added to the mixture for salting out and the mixture was extracted with diethyl ether (2 x 25mL). The diethyl ether extracts were combined and the combined diethyl ether layer was dried over anhydrous sodium sulfate and was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (hexane: ethyl acetate = 4:1 shifted to dichloromethane: methanol = I0:I) to give 124mg of cis-3cyclopropylaminomethyl-4-methylpyrrolidine as a pale brown oil. MS (CI÷) m/z: 155 (MH+). HRMS (CI+): Calcd for C 9 HI 9 N 2 (MH+): 155.1548; found: 155.1553. Reference Example 8 Synthesis of (3R,4S)-3-cyclopropylaminomethyl-4methylpyrrolidine Step I: (3R, 4S)-l-Benzyl-3-hydroxy-4-methylpyrrolidine (4.00g) was dissolved in dichloromethane (40mL). While this solution was cooled on a dry ice/acetone bath, triethylamine (3.06mL) was added. Methanesulfonyl chloride (l.70mL) was then added dropwise and the mixture was further stirred for 1 hour. Following addition of water (40mL), the temperature of the mixture was allowed to rise to room temperature and the dichloromethane layer was separated. The aqueous layer was extracted with dichloromethane (40mL) and the extract was combined with the dichloromethane layer. The combined dichloromethane layer was then washed with water, followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was dissolved in N,Ndimethylformamide (120mL). tetrabutylammonium cyanide To this solution, (5.53g) and sodium cyanide (2.05g) were added and the mixture was stirred at 80°C for 13 hours. Subsequently, the reaction mixture was concentrated under reduced pressure and water (50mL) was added to the resulting residue. The mixture was extracted with diethyl ether (2 x 200mL). The diethyl ether extracts were combined and the combined extract was washed with a saturated aqueous solution of sodium chloride, followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (hexane: ethyl acetate = 4:1) to give 3.32g of (3R, 4S)-l-benzyl-4methyl-3-pyrrolidinecarbonitrile as a brown oil. IH NMR(CDCI 3 ):6 1.22 (d, J = 7.3 Hz, 3H), 2.12 (dd, J = 8.3 Hz, 9.3 Hz, IH), 2.45-2.57 (m, IH), 2.60-2.67 (m, IH), 2.99 (dd, J = 7.3 Hz, 9.3 Hz, IH), 3.09-3.19 (m, 2H), 3.62 (s, 2H), 7.257.35 (m, 5H). MS(EI)m/z: 200 (M÷) . Step 2 : In a similar manner to Step 2 in Reference Example 7, (3R,4S)-l-benzyl-4-methyl-3-pyrrolidinecarbonitrile (3.20g) was reacted to obtain 2.98g of (3S,4S)-l-benzyl-4-methyl-3aminomethylpyrrol idine. IH NMR(CDCI 3 ):6 0.94 (d, J = 7.3 Hz, 3H), 2.03 (dd, J = 7.3 Hz, 9.3 Hz, IH), 2.11-2.26 (m, 2H), 2.31-2.43 (m, IH), 2.58 (dd, J = 8.3 Hz, 12.2 Hz, IH), 2.82 (dd, J = 5.9 Hz, 12.2 Hz, IH), 2.97-3.02 (m, 2H), 3.60 (s,2H), 7.22-7.33 (m, 5H). Step 3: In a similar manner to Step 3 in Reference Example 7, (3S,4S)-l-benzyl-4-methyl-3-aminomethylpyrrolidine (2.80g) was reacted to give 3.49g of (3R,4S)-l-benzyl-3-benzylaminomethyl4-methyl-pyrrolidine. MS (EI) m/z: 294 (M÷). HRMS (EI): Calcd for C 20 H 26 N 2 (M÷): 294.2096; found: 294.2072. Step 4 : In a similar manner to Step 4 in Reference Example ( 3R, 4S ) - l-benzyl-3-benzylaminomethyl4 -methylpyrrolidine (3.40g) was reacted to give 3.72g of ( 3R,4S)-l-benzyl-3-(Nbenzyl-N-cyclopropyl ) aminomethyl4 -methylpyrrolidine. MS (FAB÷) m/z: 335 (MH÷). HRMS (EI): Calcd for C 23 H 31 N 2 (MH+): 335.2487; found: 335.2503. Step 5: In a similar manner to Step 5 in Reference Example (3R,4S)-l-benzyl-3-(N-benzyl-N-cyclopropyl)aminomethyl-4methylpyrrolidine (3.60g) was reacted to give 1.29g of (3R, 4S)-3-cyclopropylaminomethyl-4-methylpyrrolidine. MS (CI÷)m/z: 155 (MH÷). HRMS (CI+): Calcd for C 9 HI 9 N 2 (MH+): 155.1548; found: 155.1539. Reference Example 9 Synthesis of (3S,4R)-3-cyclopropylaminomethyl-4methylpyrrolidine Step I: In a similar manner to Step 1 in Example 8, (3S,4R)-Ibenzyl-3-hydroxy-4-methylpyrrolidine (4.62g) was reacted give 3.07g of (3S,4R)-l-benzyl-4-methyl-3pyrrolidinecarbonitrile. IH NMR(CDCI 3 ):6 1.22 (d, J = 6.8 Hz, 3H), 2.13 (t,J = 9.3 Hz, IH), 2.45-2.55 (m, IH), 2.61-2.65 (m, IH), 2.99 (dd, J = 6.8 Hz, 9.3 Hz, IH), 3.09-3.19 (m, 2H), 3.62 (s, 2H), 7.27-7.34 (m, 5H). Step 2: In a similar manner to Step 2 in Reference Example 7, (3S,4R)-l-benzyl-4-methyl-3-pyrrolidinecarbonitrile (3.00g) was reacted to give 1.44g of (3R,4R)-l-benzyl-4-methyl-3aminomethylpyrrolidine. MS (EI)m/z: 204 (M+). HRMS (EI): Calcd for C 13 H 20 N 2 (M+): 204.1626; found: 204.1614. Step 3: In a similar manner to Step 3 in Reference Example 7, (3R, 4R)-l-benzyl-4-methyl-3-aminomethylpyrrolidine (l.06g) was reacted to give 1.20g of (3S,4R)-l-benzyl-3-benzylaminomethyl4-methylpyrrolidine. MS (EI) m/z: 294 (M+). HRMS (EI): Calcd for C 20 H 26 N 2 (M÷): 294.2096; found: 294.2106. Step 4: In a similar manner to Step 4 in Reference Example 7, (3S,4R)-l-benzyl-3-benzylaminomethyl-4-methylpyrrolidine (l.40g) was reacted to give 1.55g of (3S,4R)-l-benzyl-3-(Nbenzyl-N-cyclopropyl ) aminomethyl-4 -methylpyrrolidine. MS (FAB÷) m/z: 335 (MH÷). HRMS (EI): Calcd for C 23 H 31 N 2 (MH÷): 335.2487; found: 335.2498. Step 5: In a similar manner to Step 5 in Reference Example 7, (3S,4R)-!-benzyl-3-(N-benzyl-N-cyclopropyl)aminomethyl-4methylpyrrolidine (700mg) was reacted to give 215mg of (3S,4R)-3-cyclopropylaminomethyl-4-methylpyrrolidine. MS (CI+)m/z: 155 (MH÷). HRMS (CI÷): Calcd for C 9 HI 9 N 2 (MH÷): 155.1548; found: 155.1510. Reference Example I0 Synthesis of trans-3-cyclopropylaminomethyl-4trifluoromethylpyrrolidine Step I: In a similar manner to Step 1 in Example 4, transl-benzyl-4-trifluoromethyl-3-pyrrolidinecarboxylic acid (3.00g) was reacted to give 3.32g of trans-l-benzyl-4trifluoromethyl-3-pyrrolidinecarboxamide. Step 2 : In a similar manner Step 2 in Example 4, trans-l-benzyl4-trifluoromethyl-3-pyrrolidinecarboxamide (3.21g) was reacted to give 3.37g of trans-l-benzyl-3-[[(N-tert-butoxycarbonyl-Ncyclopropyl ) amino ] methyl ] -4 -tri fluoromethylpyrrolidine. MS (FAB÷) m/z: 399 (MH÷). HRMS (FAB+): Calcd for C 21 H 30 F 3 N 2 0 2 (MH÷): 399.2259; found: 399.2254. Step 3: In a similar manner to Step 3 in Example 4, trans-lbenzyl-3-[[(N-tert-but0xycarbonyl-N-cyclopropyl)amin methyl]- 4-trifluoromethylpyrrolidine (3.27g) was reacted to give 2.38g of trans-3-[[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl]-4-trifluoromethylpyrrolidine. MS (FAB÷) m/z: 309 (MH÷). HRMS (FAB+): Calcd for C 14 H 24 F 3 N 2 0 2 (MH+) : 309.1790; found: 309.1783. Step 4: In a similar manner to Step 4 in Example 4, trans-3-[[(Ntert-butoxycarbonyl-N-cyclopropyl)amino]methyl]-4trifluoromethylpyrrolidine (2.30g) was reacted to give 992mg of trans-3-cyclopropylaminomethyl-4-trifluoromethylpyrrolidine. IH NMR(CDCI 3 ): 6 0.29-0.33 (m, 2H), 0.42-0.46 (m, 2H), 2.10Elementary analysis (%): Calcd for C 9 HIsF 3 N 2 "2CF 3 COOH: C 35.79, 3.93, N 6.42; found: C 35.82, H 3.90, N 6.59. Reference Example II Synthesis of (3R,4S)-3-cyclopropylaminomethyl-4fluoropyrrolidine (Process (I)) Step I: (E)-3-Benzyloxypropenyl-(iR)-camphorsultam (21.6g) was dissolved in dichloromethane (300mL) containing trifluoroacetic acid (0.116mL). To this solution, Nmethoxymethyl-N-(trimethylsilyl)benzylamine (15.0g) was added dropwise and the mixture was further stirred for 2 hours. The mixture was sequentially washed with a saturated aqueous solution of sodium hydrogen carbonate (2 x 200mL) and then with water (200mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting pal e yellow oil was dissolved in diethyl ether (150mL) and the solution was allowed to stand for 18 hours at room temperature. The crystal formed was collected by filtration, was washed with diethyl ether, and was then dried under reduced pressure to give ll.5g of N-[[(3S,4R)-benzyl-4benzyloxypyrrolidin-3-yl]carbonyl]-(2'S)-bornane-10,2-sultam as a white crystal. The filtrate and the washing solution were combined and the combined organic layer was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = cyclohexane: ethyl acetate = 4:1) to obtain additional 8.48g of N-[[(3S,4R)-benzyl-4benzyloxypyrrolidin-3-yl ] carbonyl ] - ( 2 ' S ) -bornane-10,2-sultam. IH NMR(CDCI 3 ): 6 0.95 (s, 3H), 1.02 (s, 3H), 1.32-1.45 (m, 2H), 1.86-1.96 (m, 3H), 2.00-2.10 (m, 2H), 2.57 (dd, J=9.3 Hz, 5.3 Hz), 2.69 (dd, J= 9.8 Hz, 3.9 Hz, IH), 2.93 (dd, J= 10.3 Hz, 6.3 Hz, IH), 3.20 (t, J=9.3Hz), 3.42-3.51 (m, 3H), 3.69-3.74 (m, 2H), 3.90 (d, J=ll.7 Hz), 4.54 (d, J= Ii.7 Hz), 4.63-4.66 (m, IH), 7.22-7.31 (m, 10H). Step 2: Lithium aluminum hydride (80%, 5.56g) was suspended in tetrahydrofuran (170mL). While the suspension was cooled on a sodium chloride/ice bath, a tetrahydrofuran solution (300mL) of N-[[(3S,4R)-benzyl-4-benzyloxypyrrolidin-3-yl]carbonyl]- (2'S)-bornane-10,2-sultam (19.9g) was added dropwise and the mixture was stirred at -5°C or below for 1 hour. Subsequently, water (34mL) was carefully added dropwise to the mixture. Insoluble materials were collected by filtration and were washed with ethyl acetate (2 x 400mL). The filtrate and the washing solutions were combined and the combined organic layer was extracted with imol/L hydrochloric acid (2 x 500mL). The hydrochloric acid extracts were combined and a 30% aqueous solution of sodium hydroxide was added to make the combined solution basic (pH 14). The mixture was then extracted with diethyl ether (2 x 500mL) and the diethyl ether extracts were combined. The combined diethyl ether layer was concentrated under reduced pressure and the resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = I:i) to give 9.91g of (3R,4R)-(l-benzyl-4-benzyloxypyrrolidin-3yl)methanol as a pale yellow oil. IH NMR(CDCI 3 ): 6 2.29-2.34(m, IH), 2.40 (dd, J=10.3 Hz, 4.4 Hz, IH), 2.68 (dd, J=9.3 Hz, 2.4 Hz, IH), 2.75 (dd, J= 9.8 Hz, 6.3 Hz, IH), 3.18 (dd, J= 9.8 Hz, 6.8 Hz, IH), 3.61 (s, 2H), 3.65 (dd, J=10.3 Hz, 4.4 Hz, IH), 3.73 (dd, J=10.3 Hz, 4.4 Hz, IH), 4.07 (ddd, J= 6.3 Hz, 4.4 Hz, 2.0 Hz, IH), 4.48 (s, 2H), 7.257.35 (m, 10H). Step 3: Process (A): (3R,4R)-(l-benzyl-4-benzyloxypyrrolidin-3yl)methanol (9.80g) was dissolved in ethanol (100mL). To this solution, 10% palladium carbon (2.00g) was added and the mixture was stirred at 50°C for 21 hours under a hydrogen pressure of 3.9 x 10SPa. Subsequently, the catalyst was collected from the reaction mixture by filtration through a Celite pad. The collected catalyst and the Celite pad were washed with ethanol. The filtrate and the washing solution were combined and the combined organic layer was concentrated under reduced pressure. The resulting residue was dissolved in ethanol (100mL), followed by addition of 10% palladium carbon (2.00g). The mixture was then stirred at 50°C for 20 hours under a hydrogen pressure of 3.9 x 10SPa. Subsequently, the catalyst was collected from the reaction mixture by filtration through a Celite pad. The collected catalyst and the Celite pad were washed with ethanol. The filtrate and the washing solution were combined and the combined organic layer was concentrated under reduced pressure. The resulting residue was dried under reduced pressure to give 3.77g of (3R, 4R)-(4hydroxypyrrolidin-3-yl)methanol. IH NMR(DMSO-d 6 ): 6 1.96-2.03 (m, IH), 2.61 (dd, J=ll.6 Hz, 5.5 Hz, IH), 2.68 (dd, J=ll.6 Hz, 3.1 Hz, IH), 2.91 (dd, J= II.i Hz, 5.5 Hz, IH), 3.06 (dd, J= ii.0 Hz, 7.3 Hz, IH), 3.26 (dd, J=10.4 Hz, 7.3 Hz, IH), 3.37 (dd, J=10.4 Hz, 6.1 Hz), 3.903.93 (m, IH). Sodium hydroxide (2.70g) and dioxane (15mL) was added. was dissolved in water (25mL) To this solution, (3R,4R)-(4hydroxypyrrolidin-3-yl)methanol (l.00g) was dissolved. While the solution was cooled on an ice bath, carbobenzoxy chloride (0.97mL) was added dropwise. The mixture was stirred at 5°C or below for 1 hour, followed by dropwise addition of carbobenzoxy chloride (0.97mL). The mixture was further stirred at 5°C or below for additional 1 hour and carbobenzoxy chloride (0.97mL) was subsequently added dropwise. This was followed by Stirring for 1 hour at 5°C or below and another 1 hour at room temperature. Subsequently, the reaction mixture was extracted with dichloromethane (2 x 100mL). The dichloromethane extracts were combined, and the combined dichloromethane layer was dried over anhydrous sodium sulfate and was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = I:i shifted to ethyl acetate: methanol = 20:1) to give 1.18g of (3R, 4R)-[l-benzyloxycarbonyl-4hydroxypyrrolidin-3-yl]methanol as a milky white tar-like product. MS (EI) m/z: 251 (M÷). IH NMR(CDCI 3 ): 6 2.08-2.40 (br +m, 2H), 2.58-2.79 (br, IH), 3.20 (dd, J=ll.0 Hz, 7.3 Hz, IH), 3.32 (dt, J=ll.iHz, 5.5 Hz, IH), 3.59-3.76 (m, 4H), 4.23-4.33 (br, IH), 5.12 (s, 2H), 7.28-7.36 (m, 5H). Process (B): (3R,4R)-[l-benzyl-4-benzyloxypyrrolidin-3yl]methanol (10.0g) was dissolved in methanol (200mL). To this solution, 10% palladium carbon (3.00g) suspended in water (60mL) and ammonium formate (21.2g) were sequentially added, and the mixture was heat-refluxed for 4 hours while being stirred. Subsequently, the catalyst was collected from the reaction mixture by filtration through a Celite pad. The collected catalyst and the Celite pad were washed with a methanol/water mixture (80:20). The filtrate and the washing solution were combined and the combined solution was concentrated under reduced pressure. The resulting pale brown, tar-like material was dissolved in N,N-dimethylformamide (100mL). While this solution was cooled on an ice bath, triethylamine (9.40mL) was added, followed by dropwise addition of carbobenzoxy chloride (6.00mL). While being cooled on an ice bath, the resulting mixture was stirred for 1.5 hours andwas subsequently concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (400mL) and the solution was washed with a saturated aqueous solution of sodium chloride (2 x 100mL), was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = ethyl acetate, shifted to ethyl acetate: methanol = 20:1) to give 7.66g of (3R, 4R)-[Ibenzyloxycarbonyl-4-hydroxypyrrolidin-3-yl]methanol as a milky white tar-like product. This compound was identical to the compound obtained by Process (A). Step 4: Process (A): (3R, 4R)-(l-benzyloxycarbonyl-4hydroxypyrrolidin-3-yl)methanol (3.19g) was dissolved in N,Ndimethylformamide (91mL). While this solution was cooled on an ice bath, imidazole (6.05g) and tert-butylchlorodimethylsilane (5.74g) were sequentially added and the mixture was stirred at room temperature for 3 hours. Subsequently, the reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in diethyl ether (400mL). The diethyl ether layer was washed with a saturated aqueous solution of sodium chloride (2 x 100mL), was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 4:1) to give 5.46g of (3R, 4R)-l-benzyloxycarbonyl-3-(tertbutyldimethylsilyl)oxymethyl-4-(tertbutyldimethylsilyl)oxypyrrolidine as a colorless oil. MS (CI÷) : m/z=480(MH÷) . IH NMR(CDCI 3 ): 6 0.03 (s, 3H), 0.05 (s, 3H), 0.06 (s, 3H), 0.07 (s, 3H), 0.87 (s, 9H), 0.88 (s, 9H), 2.17-2.27 (m, IH), 3.213.28 (m, 2H), 3.48-3.67 (m, 4H), 4.21-4.28 (m, IH), 5.13 (s, 2H), 7.31-7.37 (m, 5H). (3R,4R)-l-Benzyloxycarbonyl-3-(tertbutyldimethylsilyl)oxymethyl-4-(tertbutyldimethylsilyl)oxypyrrolidine (5.46g) was dissolved in tetrahydrofuran (23mL). While this solution was cooled on an ice bath, water (23mL) and acetic acid (68mL) were sequentially added and the mixture was stirred at room temperature for 8 hours. Subsequently, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 4:1 shifted to I:i) to give 2.74g of (3R,4R)- l-benzyloxycarbonyl-3-hydroxymethyl-4-(tertbutyldimethylsilyloxy)pyrrolidine as a colorless oil. MS (CI%) : m/z=366(MH+) . IH NMR(CDCI 3 ) : 6 0.07-0.08 (m, 6H), 0.88 (s, 9H), 2.23-2.35 (m, IH), 3.21-3.30 (m, 2H), 3.58-3.72 (m, 4H), 4.17-4.25 (m, IH), 5.128 (s, IH), 5.135 (s, IH), 7.31-7.37 (m, 5H). (3R, 4R)-l-Benzyloxycarbonyl-3-hydroxymethyl-4-(tertbutyldimethylsilyloxy)pyrrolidine (2.73g) was dissolved in dichloromethane (60mL). While this solution was cooled on a sodium chloride/ice bath, triethylamine (l.21mL) was added, which was followed by dropwise addition of methanesulfonyl chloride (0.71mL) at -5°C or below. The reaction mixture was then stirred at -5°C or below for 1 hour, was washed with water (2 x 25mL), was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (60mL), followed by addition of sodium azide (l.14g) and stirring at 100°C for 2 hours. The reaction mixture was then concentrated under reduced pressure and water (30mL) was added to the resulting residue. The mixture was then extracted with diethyl ether (2 x 100mL) and the diethyl ether extracts were combined. The combined diethyl ether layer was dried over anhydrous sodium sulfate and was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 4:1) to give 3.06g of (3R,4R)-3-azidomethyl-l-benzyloxycarbonyl-4-(tert- butyldimethylsilyl)oxypyrrolidine as a colorless oil. MS (CI÷) :m/z=391 (MH+). ZH NMR(CDCI 3 ): 6 0.07-0.09 (m, 3H), 2.23-2.34 (m, IH), 3.193.25 (m, 2H), 3.27-3.40 (m, 2H), 3.60-3.71 (m, 2H), 4.11-4.17 (m, IH), 5.13 (s, 2H), 7.31-7.37 (m, 5H). (3R, 4R)-3-Azidomethyl-l-benzyloxycarbonyl-4-(tertbutyldimethylsilyl)oxypyrrolidine (3.05g) was dissolved in tetrahydrofuran (50mL). While this solution was cooled on an ice bath, tetrabutylammonium fluoride (imol/L tetrahydrofuran solution, 13.3mL) was added dropwise and the mixture was stirred for additional 1 hoUr. Subsequently, a saturated aqueous solution of sodium chloride 70mL) was added and the mixture was extracted with ethyl acetate (150mL, 100mL). The ethyl acetate extracts were combined and the combined solvent was dried over anhydrous sodium sulfate and was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = ethyl acetate) to give 2.01g of (3R, 4R)-3-azidomethyl-l-benzyloxycarbonyl-4-hydroxypyrrolidine as a milky white syrup-like product. Process (B) : (3R, 4R)-[l-Benzyloxycarbonyl-4hydroxypyrrolidin-3-yl]methanol (3.00g), sodium azide (2.32g), triphenylphosphine (3.43g) and N,N-dimethylformamide (60mL) were mixed with each other. While the mixture was cooled on an ice bath, a dichloromethane solution (14mL) of carbon tetrabromide (4.34g) was added dropwise. The reaction mixture was stirred for 25 hours at room temperature and additional 2 hours at 60°C, followed by addition of methanol (5mL) and concentration under reduced pressure. The resulting residue was dissolved in ethyl acetate (200mL) and was washed with a saturated aqueous solution of sodium chloride (2 x 50mL), followed by drying over anhydrous sodium sulfate and concentration under reduce pressure. The resulting residue was purified on silica gel column (eluant = ethyl acetate: hexane = 2:1) to give 2.94g of (3R,4R)-3-azidomethyl-lbenzyloxycarbonyl-4-hydroxypyrrolidine as a pale brown syruplike product. This compound was identical to the compound obtained by Process (A). Process (C): (3R,4R)-[l-Benzyloxycarbonyl-4hydroxypyrrolidin-3-yl]methanol (150mg) was dissolved in dichloromethane (12mL) and 2,4,6-collidine (0.79mL) was added. While this solution was cooled on an ice bath, methanesulfonyl chloride (46.2 L) was added dropwise. The mixture was then stirred for 2 hours on the ice bath and was allowed to stand for 15 hours in a refrigerator (3°C). Subsequently, the reaction mixture was sequentially washed with water (2mL), Imol/L hydrochloric acid (2 x 2mL), and a saturated aqueous solution of sodium chloride (2 x 2mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 1:2 shifted to ethyl acetate) to give 38.7mg of (3R,4R)-l-benzyloxycarbonyl-3methanesulfonyloxy-4-methanesulfonyloxymethylpyrrolidine as a pale yellow syrup-like product and 133mg of (3R,4R)-Ibenzyloxycarbonyl-3-hydroxy-4methanesulfonyloxymethylpyrrolidine as a white syrup-like product. (3R,4R)-l-Benzyloxycarbonyl-3-hydroxy-4methanesulfonyloxymethylpyrrolidine (125mg) was dissolved in N,N-dimethylformamide (3mL) and sodium azide (50.0mg) was added. The mixture was stirred at 100°C for 1 hour and was then concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (5mL) and the solution was washed with water (2 x imL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (eluant = ethyl acetate) to give 91.0mg of (3R,4R)-3azidomethyl-l-benzyloxycarbonyl-4-hydroxypyrrolidine as a milky white syrup-like product. The compound was identical to the compound obtained by Process (A). Step 5: Process (A): (3R, 4R)-3-Azidomethyl-l-benzyloxycarbonyl-4hydroxypyrrolidine (l.20g) was dissolved in dichloromethane (40mL). While this solution was cooled on a sodium chloride/ice bath, diethylaminosulfur trifluoride (l.20mL) was added dropwise and the mixture was stirred at room temperature for 3 hours. The reaction vessel was again cooled on a sodium chloride/ice bath and diethylaminosulfur trifluoride (0.57mL) was again added dropwise. The mixture was then stirred at room temperature for 2 hours. While the reaction mixture was cooled on an ice bath, a saturated aqueous solution of sodium hydrogen carbonate (40mL) was added dropwise and the dichloromethane layer was separated. The dichloromethane layer was sequentially washed with a saturated aqueous solution of sodium hydrogen carbonate (2 x 20mL) and water (20mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 2:1) to give 726mg of (3R,4S)-3-azidomethyl-lbenzyloxycarbonyl-4-fluoropyrrolidine as a pale brown oil. MS (CI+):m/z=279 (MH÷). IH NMR(CDCI 3 ): 6 2.34-.2.54 (m, IH), 3 22 (dt, J=ll.0 Hz, 2.4 Hz, Process (B) :(3R, 4R)-3-Azidomethyl-l-benzyloxycarbonyl-4hydroxypyrrolidine (1.79g) was dissolved in toluene (56mL). While this solution was cooled on an ice bath, 1,8diazabicyclo[5.4.0]undec-7-ene (2.03mL) was added. This was followed by dropwise addition of perfluoro-l-octanesulfonyl fluoride (2.80mL) and stirring for another 1 hour. Insoluble materials were removed from the reaction mixture by filtration and were washed with toluene. The filtrate and the washing solution were combined and the combined organic layer was concentrated under reduced pressure. The resulting residue was then purified on a silica gel column (eluant = hexane: ethyl acetate = 2:1) to give 1.58g of (3R, 4S)-3-azidomethyl-lbenzyloxycarbonyl-4-fluoropyrrolidine as a pale brown syruplike product. The compound was identical to the compound obtained by Process (A). Step 6: (3R, 4S)-3-Azidomethyl-l-benzyloxycarbonyl-4fluoropyrrolidine (1.35g) was dissolved in ethanol 30mL). To this solution, platinum oxide (IV) (190mg) was added and the mixture was stirred at room temperature for 2 hours in a stream of hydrogen (provided from a balloon). Subsequently, the catalyst was collected from the reaction mixture by filtration through a Celite pad. The collected catalyst and the Celite pad were washed with ethanol. The filtrate and the washing solution were combined and the combined organic layer was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = ethyl acetate: methanol = I0:i) to give 1.13g of (3S,4S)-3-aminomethyl-lbenzyloxycarbonyl-4-fluoropyrrolidine as a pale brown oil. MS (CI+):m/z=253(MH÷). Step 7: (3S,4S)-3-Aminomethyl-l-benzyloxycarbonyl-4fluoropyrrolidine (l.10g) was dissolved in methanol (13mL). To this solution, molecular sieves 4A (440mg) and benzaldehyde (0.44mL) were sequentially added and the mixture was stirred at room temperature for 1 hour. Subsequently, a boranepyridine complex (0.44mL) was added and the mixture was further stirred at room temperature for 3.5 hours. This was followed by addition of 6mol/L hydrochloric acid (7.3mL) and stirring at room temperature for 1 hour. Subsequently, a 30% aqueous solution of sodium hydroxide was added to make the mixture basic and the mixture was extracted with diethyl ether (2 x 100mL). The diethyl ether extracts were combined and the combined diethyl ether layer was dried over anhydrous sodium sulfate and was thenconcentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 4:1 shifted to I:I) to give 1.18g of (3S,4S)-3-benzylaminomethyl-l-benzyloxycarbonyl-4fluoropyrrolidine as a colorless tar-like product. MS (CI÷):m/z=343 (MH÷). Step 8: (3S,4S)-3-Benzylaminomethyl-l-benzyloxycarbonyl-4fluoropyrrolidine (l.15g was dissolved in methanol (21mL). To this solution, molecular sieves 3A (l.05g), acetic acid (l.92mL), [(l-ethoxycyclopropyl)oxy]trimethylsilane (2.70mL), and sodium cyanoborohydride (633mg) were added and the mixture was heat-refluxed for 2 hours while being stirred. Subsequently, insoluble materials were removed from the reaction mixture by filtration through a Celite pad. The insoluble materials and the Celite pad were washed with methanol. The filtrate and the washing solution were combined and a 2mol/L aqueous solution of sodium hydroxide was added to make the combined organic layer basic (pHl4). Methanol was then removed under reduced pressure and the residue was extracted with diethyl ether (2 x 100mL). The diethyl ether extracts were combined and the combined diethyl ether layer was dried over anhydrous sodium sulfate and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 4:1) to give 1.26g of (3S,4S)-3-(N-benzyl-Ncyclopropyl)aminomethyl-l-benzyloxycarbonyl-4fluoropyrrolidine as a colorless tar-like product. MS (EI) m/z:=382 (M+). Step 9: (3S,4S)-3-(N-Benzyl-N-cyclopropyl)aminomethyl-lbenzyloxycarbonyl-4-fluoropyrrolidine (1.22g) was dissolved in ethanol (14mL). To this solution, 10% palladium carbon (150mg) was added and the mixture was stirred at room temperature for 4 hours in a stream of hydrogen (provided from a balloon). Subsequently, the catalyst was collected from the reaction mixture by filtration through a Celite pad. The collected catalyst and the Celite pad were washed with ethanol. The filtrate and the washing solution were combined and the combined organic layer was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = ethyl acetate: methanol = 20:1). The eluate was distilled under reduced pressure to give 414mg of (3R, 4S)-3cyclopropylaminomethyl-4-fluoropyrrolidine as a colorless oil. MS (CI+): m/z=159 (MH+). HRMS (CI÷): Calcd for CsHI 6 FN 2 : 159.1298; found: 159.1316. Reference Example 12 Synthesis of (3R,4S)-3-cyclopropylaminomethyl-4fluoropyrrolidine (Process (II)) Step I: (3R,4R)-(4-Hydroxypyrrolidin-3-yl)methanol (l.18g) was dissolved in ethanol (25mL) and triethylamine (l.40mL) was added to the solution. While this mixture was cooled on a sodium chloride/ice bath, benzyl bromide (l.10mL) was added dropwise. The mixture was then stirred at room temperature for 1 hour and was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = ethyl acetate: methanol = 20:1) to give 1.02g of (3R, 4R)-(Ibenzyl-4-hydroxypyrrolidin-3-yl)methanol as a milky white syrup-like product. MS (EI+): m/z=207 (M+). HRMS (EI÷): Calcd for C 12 HITNO 2 : 207.1259; found: 207.1237. Step 2: (3R, 4R)-(l-Benzyl-4-hydroxypyrrolidin-3-yl)methanol (1.36g) was dissolved in dichloromethane (14mL). While this solution was cooled on an dry ice/acetone bath, triethylamine (0.83mL) was added, followed by dropwise addition of methanesulfonyl chloride (0.46mL) and stirring for 30min. Water (10mL) was then added to the reaction mixture and the temperature of the mixture was allowed to rise to room temperature. The mixture was then diluted with dichloromethane (20mL) and the dichloromethane layer was collected. The collected dichloromethane layer was washed with water (2 x 10mL), was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (hexane: ethyl acetate = i:I shifted to ethyl acetate: methanol = 20:1). From a fraction eluted at hexane: ethyl acetate = i:i, 585mg of (3R, 4R)-Ibenzyl-3-methanesulfonyloxy-4methanesulfonyloxymethylpyrrolidine was obtained as a milky white syrup-like product. MS (EI+): m/z=363 (M÷). HRMS (EI+) : Calcd for C 14 H 21 NO 6 S 2 : 363.0810; found: 363.0804. Also, 840mg of (3R,4R)-l-benzyl-3-hydroxy-4methanesulfonyloxymethylpyrrolidine was obtained as a white crystal from a fraction eluted at ethyl acetate: methanol = 20:1. MS (EI+): m/z=285 (M÷). HRMS (EI+): Calcd for C 13 HI 9 NO 4 S: 285.1035; found: 285.1045. Step3: (3R, 4R)-l-Benzyl-3-hydroxy-4methanesulfonyloxymethylpyrrolidine (835mg), sodium azide (381mg), and N,N-dimethylformamide (12mL) were mixed with one another and the mixture was stirred at 120°C for 1 hour. Subsequently, the reaction mixture was concentrated under reduced pressure. To the resulting residue, water (10mL) was added and the mixture was extracted with diethyl ether (2 x 30mL). The diethyl ether extracts were combined and the combined extract was dried over anhydrous sodium sulfate and was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = ethyl acetate: methanol = 20:1) to give 576mg of (3R,4R)-3-azidomethyl-lbenzyl-4-hydroxypyrrolidine as a pale brown oil. MS (EI÷): m/z=232 (M÷). HRMS (EI÷): Calcd for C 12 HI 6 N 4 0: 232.1324; found: 232.1309. Step 4: (3R,4R)-3-Azidomethyl-l-benzyl-4-hydroxypyrrolidine (566mg) was dissolved in dichloromethane (9mL). While this solution was cooled on an ice bath, diethylaminosulfur trifluoride (0.39mL) was added dropwise and the mixture was stirred at room temperature for 2 hours. While the reaction vessel was cooled on an ice bath, a saturated aqueous solution of sodium hydrogen carbonate (9mL) was added, and the mixture was diluted with dichloromethane (15mL). The dichloromethane layer was collected and the collected dichloromethane layer was washed with a saturated aqueous solution of sodium hydrogen carbonate (10mL) and then water (10mL), was dried over anhydrous sodium sulfate, and was concentrated under reduced pressure. The resulting residue was purified on a silica gel column(eluant = hexane: ethyl acetate = 4:1). From the first half fraction, 76.7mg of (3R,4R)-3-azidomethyl-lbenzyl-4-fluoropyrrolidine was obtained as a pale brown oil. MS (EI÷) :m/z=234 (M÷). HRMS (EI+): Calcd for C 12 HI 5 FN 4 : 234.1281; found: 234.1263. From the second half fraction, 220mg of (3R, 4S)-3azidomethyl-l-benzyl-4-fluoropyrrolidine was obtained as a pale brown oil. MS (EI+): m/z=234 (M÷). HRMS (EI+): Calcd for C 12 HIsFN 4 : 234.1281; found: 234.1269. Step 5: (3R,4S)-3-Azidomethyl-l-benzyl-4-fluoropyrrolidine (215mg) was dissolved in ethanol (3mL). To this solution, platinum oxide (IV) (30.0mg) was added and the mixture was stirred at room temperature for 5 hours in a stream of hydrogen (provided from a balloon). Subsequently, the catalyst was removed from the reaction mixture by filtration through a Celite pad. The removed catalyst and the Celite pad were washed with ethanol. The filtrate and the washing solution were combined and the combined organic layer was concentrated under reduced pressure to obtain 191mg of (3S,4S)-3aminomethyl-l-benzyl-4-fluoropyrrolidine as a brown oil. MS (CI÷): m/z=209 (MH÷). HRMS (CI÷): Calcd for C 12 HIsFN 2 : 209.1454; found: 209.1465. Step 6: (3S,4S)-3-Aminomethyl-l-benzyl-4-fluoropyrrolidine (186mg) was dissolved in methanol (4mL). To this solution, molecular sieves 4A (80.0mg) and benzaldehyde (90.SzL) were sequentially added and the mixture was stirred at room temperature for 1 hour. Subsequently, a borane-pyridine complex (90.2 L) was added and the mixture was further stirred at room temperature for 3 hours. This was followed by addition of 6mol/L hydrochloric acid (l.5mL) and stirring for 1 hour. Subsequently, a 6mol/L aqueous solution of sodium hydroxide was added to make the mixture basic and the mixture was extracted with diethyl ether (3 x 10mL). The diethyl ether extracts were combined and the combined diethyl ether layer was dried over anhydrous sodium sulfate and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl ace[ate = 4:1) to give 179mg of (3S,4S)-l-benzyl-3benzylaminomethyl-4-fluoropyrrolidine as a pale brown oil. MS (CI+): m/z = 299 (MH+). HRMS (CI÷): Calcd for C 19 H 24 FN 2 : 299.1924; found: 299.1960. Step 7: (3S,4S)-l-Benzyl-3-benzylaminomethyl-4-fluoropyrrolidine (175mg) was dissolved in methanol (2mL). To this solution, molecular sieves 3A (180mg), acetic acid (0.36mL), [(Iethoxycyclopropyl)oxy]trimethylsilane (0.47mL) and sodium cyanoborohydride (ll0mg) were added and the mixture was heatrefluxed for 3 hours while being stirred. Subsequently, insoluble materials were removed from the reaction mixture by filtration through a Celite pad. The insoluble materials and the Celite pad were washed with methanol. The filtrate and the washing solution were combined and a 2mol/L aqueous solution of sodium hydroxide was added to make the combined organic layer basic (pHl4). Methanol was then removed under reduced pressure and the residue was extracted with diethyl ether (3 x 100mL). The diethyl ether extracts were combined and the combined diethyl ether layer was dried over anhydrous sodium sulfate and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 4:1) to give 172mg of (3R,4S)-3-(Nbenzyl-N-cyclopropyl)aminomethyl-l-benzyl-4-fluoropyrrolidine as a colorless tar-like product. MS (CI÷):m/z=339 (MH÷). HRMS (CI+): Calcd for C 22 H 28 FN 2 : 339.2237; found: 339.2285. Step 8: (3R, 4S)-3-(N-Benzyl-N-cyclopropyl)aminomethyl-l-benzyl-4fluoropyrrolidine (170mg) was dissolved in ethanol (10mL). To this solution, 10% palladium carbon (200mg) and chloroform (0.17mL) were added and the mixture was stirred at 50°C for 23 hours under a hydrogen pressure of 3.9x105Pa. Subsequently, palladium carbon was removed from the reaction mixture by filtration through a Celite pad. The removed palladium carbon and the Celite pad were washed with ethanol. The filtrate and the washing solution were then combined and the combined organic layer was concentrated under reduced pressure. To the resulting residue, a 30% aqueous solution of sodium hydroxide (approximately ImL) was added. Subsequently, sodium chloride was added to saturation and the mixture was extracted with diethyl ether (3 x 10mL). The diethyl ether extracts were combined and the combined diethyl ether layer was dried over anhydrous sodium sulfate and was then concentrated under reduced pressure to give 65.4mg of (3R, 4S)-3cyclopropylaminomethyl-4-fluoropyrrolidine as a pale brown oil. This compound was identical to the compound obtained in Reference Example II (Process (I)). Reference Example 13 Synthesis of (3R,4R)-3-cyclopropylaminomethyl-4fluoropyrrolidine Step I: (3R,4R)-[l-Benzyloxycarbonyl-4-hydroxypyrrolidin-3yl]methanol (2.50g), triphenylphosphine (5.74g), and benzoic acid (2.55g) were dissolved in tetrahydrofuran (60mL). While this solution was cooled on a sodium chloride/ice bath, azodicarboxylic acid diethyl ester (40% toluene solution, 9.53mL) was added dropwise. The mixture was stirred for 1 hour at 0°C or below and then for additional 2 hours at room temperature and was subsequently concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 2:1). The eluted pale brown tar-like material was dissolved in ethanol (60mL). To this solution, potassium carbonate (4.07g) dissolved in water (30mL) was added and the mixture was heat-refluxed for 3 hours while being stirred. Subsequently, the reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in dichloromethane (200mL). The dichloromethane solution was washed with a saturated aqueous solution of sodium chloride (2 x 50mL), was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = ethyl acetate: methanol = i0:I) to give 2.04g of (3R,4S)-[Ibenzyloxycarbonyl-4-hydroxypyrrolidin-3-yl]methanol as a milky white syrup-like product. MS (EI)m/z=251 (M÷). Step 2: (3R, 4S)-[l-Benzyloxycarbonyl-4-hydroxypyrrolidin-3yl]methanol (2.33g), sodium azide (l.81g), triphenylphosphine (2.67g), and N,N-dimethylformamide (46mL) were mixed with one another. While this mixture was cooled on an ice bath, a dichloromethane solution (10mL) of carbon tetrabromide (3.38g) was added dropwise. The reaction mixture was stirred for 13 hours at room temperature and additional 3 hours at 60°C, followed by addition of methanol (3mL) and concentration under reduced pressure. The resulting residue was dissolved in ethyl acetate (200mL) and was washed with a saturated aqueous solution of sodium chloride (2 x 50mL), followed by drying over anhydrous sodium sulfate and concentration under reduce pressure. The resulting residue was purified on a silica gel column (eluant = ethyl acetate: hexane = 2:1) to give 2.18g of (3R, 4S)-3-azidomethyl-l-benzyloxycarbonyl-4-hydroxypyrrolidine as a milky white syrup-like product. MS (FAB+): m/z=277 (MH+). Step 3: (3R, 4S)-3-Azidomethyl-l-benzyloxycarbonyl-4hydroxypyrrolidine (300mg) was dissolved in dichloromethane (6mL). While this solution was cooled on an ice bath, diethylaminosulfur trifluoride (0.43mL) was added dropwise. The mixture was stirred at room temperature for 4 hours. While the reaction vessel was cooled on an ice bath, a saturated aqueous solution of sodium hydrogen carbonate (6mL) was added and the dichloromethane layer was collected. The collected dichloromethane layer was washed with a saturated aqueous solution of sodium chloride (2 x 2mL), was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 2:1) to give 211mg of a mixture of (3R,4R)-3-azidomethyl-lbenzyloxycarbonyl-4-fluoropyrrolidine and 3-azidomethyl-lbenzyloxycarbonyl-3-pyrroline. Step 4: Platinum oxide (IV) (50.0mg) was suspended in ethanol (7mL) and the suspension was stirred at room temperature for 30min in a stream of hydrogen (provided from a balloon). To this suspension, an ethanol solution (3mL) of a mixture (551mg) of (3R,4R)-3-azidomethyl-l-benzyloxycarbonyl-4fluoropyrrolidine and 3-azidomethyl-l-benzyloxycarbonyl-3pyrroline was added, and the mixture was stirred at room temperature for 5 hours in a stream of hydrogen (provided from a balloon). Subsequently, the catalyst was removed from the reaction mixture by filtration and was washed with ethanol. The filtrate and the washing solution were combined and the combined organic layer was concentrated under reduced pressure. The resulting residue was then purified on a silica gel column (eluant = ethyl acetate shifted to ethyl acetate: methanol = i0:i) to give 313mg of a mixture of (3S,4R)-3-aminomethyl-lbenzyloxycarbonyl-4-fluoropyrrolidine and 3-aminomethyl-lbenzyloxycarbonyl-3-pyrroline. Step 5: A mixture (310mg) of (3S,4R)-3-aminomethyl-l- benzyloxycarbonyl-4-fluoropyrrolidine and 3-aminomethyl-lbenzyloxycarbonyl-3-pyrroline was dissolved in methanol (4mL). To this solution, molecular sieves 4A (130mg) and benzaldehyde (0.13mL) were sequentially added and the mixture was stirred at room temperature for 1 hour. Subsequently, a borane- pyridine complex (0.19mL) was added and the mixture was further stirred at room temperature for 4 hours. This was followed by addition of 6mol/L hydrochloric acid (2mL) and stirring at room temperature for 1 hour. Subsequently, a 30% aqueous solution of sodium hydroxide was added to make the mixture basic and the mixture was extracted with diethyl ether (3 x 10mL). The diethyl ether extracts were combined and the combined diethyl ether layer was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = dichloromethane: methanol = i0:I) to give 177mg of (3S,4R)-3-benzylaminomethyl-l-benzyloxycarbonyl-4fluoropyrrolidine as a pale yellow oil. MS (FAB÷): m/z = 343 (MH÷). HRMS (FAB÷): Calcd for C 20 H 24 FN 2 0 2 : 343.1822; found: 343.1815. Step 6: (3S,4R)-3-Benzylaminomethyl-l-benzyloxycarbonyl-4fluoropyrrolidine (170mg) was dissolved in methanol (5mL). To this solution, molecular sieves 3A (160mg), acetic acid (0.29mL), [(l-ethoxycyclopropyl)oxy]trimethylsilane (0.40mL), and sodium cyanoborohydride (93.5mg) were added and the mixture was heat-refluxed for 3 hours while being stirred. Subsequently, insoluble materials were removed from the reaction mixture by filtration through a Celite pad. The insoluble materials and the Celite pad were washed with methanol. The filtrate and the washing solution were combined and a 2mol/L aqueous solution of sodium hydroxide was added to make the combined organic layer basic (pH>12). Methanol was then removed under reduced pressure and the residue was extracted with diethyl ether (3 x 10mL). The diethyl ether extracts were combined and the combined diethyl ether layer was dried over anhydrous sodium sulfate and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 2:1) to give 166mg of (3S,4R)-3-(N-benzyl-Ncyclopropyl)aminomethyl-l-benzyloxycarbonyl-4fluoropyrrolidine as a colorless tar-like product. MS (FAB+): m/z = 383 (MH+). HRMS (FAB+): Calcd for C 23 H 28 FN 2 0 2 :383.2135; found:383.2119. Step 7: (3S,4R)-3-(N-Benzyl-N-cyclopropyl)aminomethyl-lbenzyloxycarbonyl-4-fluoropyrrolidine (160mg) was dissolved in ethanol (3mL). To this solution, 10% palladium carbon (20.0mg) was added and the mixture was stirred at room temperature for hours in a stream of hydrogen (provided from a balloon). Subsequently, the catalyst was collected from the reaction mixture by filtration through a Celite pad. The collected catalyst and the Celite pad were washed with ethanol. The filtrate and the washing solution were combined and the resulting residue was purified on a silica gel column (eluant = ethyl acetate: methanol = 20:1, shifted to dichloromethane: methanol = I0:I) to give 50.7mg of (3R, 4R)-3cyclopropylaminomethyl-4-fluoropyrrolidine as a colorless oil. MS (FAB+): m/z = 159 (MH+). HRMS (FAB+): Calcd for CBHI 6 FN 2 : 159.1298; found: 159.1286. Reference Example 14 Synthesis of (3R,4S)-3-[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl-4-fluoromethylpyrrolidine Step i: (iS,5R)-7-[(IR)-l-Phenylethyl]-3-oxa-7azabicyclo[3.3.0]octane-2-one (7.73g, 33.4mmoi) was dissolved in ethanol (92mL). To this solution, cyclopropylamine (46.3mi) was added, and the mixture was stirred at 80°C for 44 hours and was subsequently concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (300mL) and the solution was washed with water (2 x 50mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. To the resulting residue, diisopropyl ether (300mL) was added and the mixture was heated to form crystal and was then concentrated to approximately 1/2. The formed crystal was collected by filtration and the collected crystal was washed with diisopropyl ether and was dried under reduced pressure to give 4.41g of (3R, 4S)-N-cyclopropyl-4hydroxymethyl-l-[(IS)-l-phenylethyl]pyrrolidine-3-carboxamide as a white crystal. The filtrate and the washing solution were combined and the combined solvent was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = I:I, shifted to ethyl acetate) to obtain additional 1.50g of (3R, 4S)-N-cyclopropyl-4-hydroxymethyl-l-[(iS)-lphenylethyl]pyrrolidine-3-carboxamide. The total amount of the compound was 5.91g. MS (EI)m/z = 288 (M+). Elementary analysis (%): Calcd for C 17 H 24 N 2 0 2 "0.2H 2 0: C 69.93, H 8.42, N 9.59; found: C 70.16, H 8.32, N 9.60. Step 2: (3R,4S)-N-Cyclopropyl-4-hydroxymethyl-l-[(IS)-lphenylethyl]pyrrolidine-3-carboxamide (7.54g) was dissolved in N,N-dimethylformamide (180mL). While this solution was cooled on an ice bath, imidazole (2.67g) and tertbutylchlorodimethylsilane (4.72g) were sequentially added. The mixture was stirred at room temperature for 90min and was subsequently concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (300mL) and the solution was washed with water (2 x 100mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (eluant = ethyl acetate) to give 7.05g of (3R,4S)-N-cyclopropyl-4-(tert-butyldimethylsilyl)oxymethyl-l- [(IS)-l-phenylethyl]pyrrolidine-3-carboxamide as a pale yellow tar-like product. MS (EI) m/z: = 402 (M÷). Step 3: (3R,4S)-N-Cyclopropyl-4-(tertbutyldimethylsilyl)oxymethyl-l-[(IS)-lphenylethyl]pyrrolidine-3-carboxamide (7.00g) was dissolved in toluene (70mL). To this solution, borane-dimethyl sulfide complex (2.20mL) was added and the mixture was heat-refluxed for 5 hours while being stirred. Subsequently, the reaction mixture was allowed to cool to room temperature. Following addition of a 10% aqueous solution of sodium carbonate (42mL), the mixture was stirred at 100°C for 1 hour and the toluene layer was separated. The toluene layer was washed with water (2 x 30mL), was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 4:1) to give 4.78g of (3S,4S)-4-(tertbutyldimethylsilyl)oxymethyl-3-cyclopropylaminomethyl-l-[(IS)- l-phenylethyl]pyrrolidine as a colorless oil. Step 4: (3S,4S)-4-(tert-Butyldimethylsilyl)oxymethyl-3cyclopropylaminomethyl-l-[(IS)-l-phenylethyl]pyrrolidine (4.70g) was dissolved in dichloromethane (70mL). To this solution, di-tert-butyldicarbonate (2.77g) was added and the mixture was stirred at room temperature for 2 hours. Subsequently, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 4:1, shifted to I:i) to give 5.28g of (3R,4S)-3-[(N-tertbutoxycarbonyl-N-cyclopropyl)amino]methyl-4-(tertbutyldimethylsilyl)oxymethyl-l-[(iS)-l-phenylethyl]pyrrolidine as a colorless oil. Step 5: Process (A): (3R,4S)-N-Cyclopropyl-4-hydroxymethyl-l- [(IS)-l-phenylethyl]pyrrolidine-3-carboxamide (1.49g) was dissolved in toluene (15mL). To this solution, a boranedimethyl sulfide complex (0.65mL) was added and the mixture was heat-refluxed for 6 hours while being stirred. Subsequently, the reaction mixture was allowed to cool to room temperature. Following addition of a 10% aqueous solution of sodium carbonate (12.4mL), the mixture was stirred at 100°C for 1 hour and the toluene layer was separated. The toluene layer was then washed with water (10mL) and was dried over anhydrous sodium sulfate. Following addition of di-tert- butyldicarbonate (l.13g), the mixture was stirred at room temperature for 30min and was subsequently allowed to stand overnight. The reaction mixture was then concentrated under reduced pressure and the resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = i:I) to give 1.50g of (3R,4S)-3-[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl-4-hydroxymethyl-l-[(IS)-lphenylethyl]pyrrolidine as pale brown crystal. Process (B): (3R, 4S)-3-[(N-tert-Butoxycarbonyl-Ncyclopropyl)amino]methyl-4-(tert-butyldimethylsilyl)oxymethyl- l-[(IS)-l-phenylethyl]pyrrolidine (3.02g) was dissolved in tetrahydrofuran (45mL). While this solution was cooled on an ice bath, tetrabutylammonium fluoride (Imol/L tetrahydrofuran solution, 7.42mi) was added dropwise and the mixture was stirred at room temperature for 2 hours. Subsequently, a saturated aqueous solution of sodium chloride (60mL) was added and the mixture was extracted with ethyl acetate (2 x 150mL). The ethyl acetate extracts were combined and the combined ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride (2 x 100mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was dissolved in ethyl acetate (10mL) and the formed crystal was collected by filtration, was washed with a small amount of ethyl acetate, and was then dried under reduced pressure to give 781mg of (3R,4S)-3-[(N- tert-butoxycarbonyl-N-cyclopropyl)amino]methyl-4hydroxymethyl-l-[(IS)-l-phenylethyl]pyrrolidine as a white crystal. The filtrate and the washing solution were combined and the combined organic layer was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = I:i) to give additional 1.43g of (3R,4S)-3-[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl-4-hydroxymethyl-l-[(IS)-lphenylethyl]pyrrolidine. The total amount of the compound was 2.21g. MS (EI)m/z: = 374 (M÷). Elementary analysis (%): Calcd for C 22 H 34 N 2 0 3 : C 70.55, H 9.15, N 7.48; found: C 70.56, H 9.29, N 7.52. Step 6: (3R, 4S)-3-[(N-tert-Butoxycarbonyl-Ncyclopropyl)amino]methyl-4-hydroxymethyl-l-[(IS)-lphenylethyl]pyrrolidine (2.66g) was dissolved in dichloromethane (40mL). While this solution was cooled on a sodium chloride/ice bath, triethylamine (l.05mL) was added. This was followed by dropwise addition of methanesulfonyl chloride (0.58mL). After being stirred at -5°C for 30min, the reaction mixture was washed with water, was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was dissolved in tetrahydrofuran (21mL). To this solution, tetrabutylammonium fluoride (imol/L tetrahydrofuran solution, 21.3mL) was added and the mixture was heat-refluxed for 2 hours while being stirred. The reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate (200mL). The ethyl acetate solution was washed with water (2 x 50mL), was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = hexane: ethyl acetate = 4:1, shifted to I:i) to give 1.13g of (3R, 4S)- 3-[(N-tert-butoxycarbonyl-N-cyclopropyl)amino]methyl-4fluoromethyl-l-[(IS)-l-phenylethyl]pyrrolidine as a pale brown tar-like product. MS (EI) m/z = 376 (M÷). Step 7: (3R, 4S)-3-[ N-tert-Butoxycarbonyl-Ncyclopropyl)amino]methyl-4-fluoromethyl-l-[(IS)-lphenylethyl]pyrrolidine (l.10g) was dissolved in methanol (20mL). To this solution, a suspension of 10% palladium carbon (230mg) in water (4mL) and ammonium formate (921mg) were sequentially added and the mixture was heat-refluxed for 90min while being stirred. Subsequently, the catalyst was removed from the reaction mixture by filtration through a Celite pad. The removed catalyst and the Celite pad were washed with ethanol containing 20% water. The filtrate and the washing solution were combined and the combined solution was concentrated under reduced pressure. Water (20mL) was then added to the resulting residue. While this mixture was cooled on an ice bath, a 30% aqueous solution of sodium hydroxide was added to make the mixture basic (pHl4). The mixture was subsequently extracted with dichloromethane (50mL x 2). The dichloromethane extracts were combined, washed with water (2 x 20mL), and the combined dichloromethane layer was dried over anhydrous sodium sulfate and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant = dichloromethane: methanol = 20:1) to give 684mg of (3R,4S)-3-[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl-4-fluoromethylpyrrolidine as a pale brown tar-like product. Reference Example Synthesis of (3R, 4R)-3-cyclopropylaminomethyl-4methylpyrrolidine-trifluoroacetate Step I: l-Benzyl-4-(R)-methyl-3-(R)-[(4-(S)-phenyl-2oxazolidinone-3-yl)carbonyl]pyrrolidine (150g) was dissolved in cyclopropylamine (650mL). The mixture was stirred at room temperature for 23 hours and was subsequently concentrated under reduced pressure. To the resulting residue, diisopropyl ether (800mL) was added and the mixture was stirred at room temperature for 70min. The resulting crystal was then collected by filtration. The collected crystal was then dissolved in dichloromethane (800mL) and the solution was extracted with imol/L hydrochloric acid (2 x 400mL). The imol/L hydrochloric acid extracts were combined. While the combined solution was cooled on an ice bath, a 30% aqueous solution of sodium hydroxide was added to make the solution basic (pHl3). The resulting crystal was collected by filtration, was sequentially washed with water and diisopropyl ether, and was then dried under reduced pressure to give 52.2g of (3R,4R)-l-l-benzyl-N-cyclopropyl-4-methyl-3pyrrolidinecarboxamide as a white crystal. Step 2: (3R,4R)-l-Benzyl-N-cyclopropyl-4-methyl-3pyrrolidinecarboxamide (70.0g) was dissolved in toluene (700mL). While this solution was cooled on an ice bath, a borane-dimethyl sulfide complex (90%, 34.3mL) was added dropwise. The mixture was then stirred for 15min and was heatrefluxed. After the reaction mixture was cooled to room temperature, a 10% aqueous solution of Na 2 CO 3 (400mL) was added and the mixture was stirred at 100°C for 2 hours. The mixture was cooled to room temperature and the toluene layer was separated. The toluene layer was then washed with water (2 x 250mL), was dried over anhydrous sodium sulfate, and was concentrated under reduced pressure. The resulting residue was purified by distillation under reduced pressure to obtain (3S,4R)-l-benzyl-3-cyclopropylaminomethyl-4-methylpyrrolidine (62.1g) as a colorless oil. Step 3: (3S,4R)-liBenzyl-3-cyclopropylaminomethyl-4methylpyrrolidine (25.0g) was dissolved in ethanol (200mL). To this solution, trifluoroacetic acid (15.7mL) and 10% palladium carbon (12.5g) were added and the mixture was stirred at room temperature for 9 hours under a hydrogen pressure of 3.9x105pa. The catalyst was collected from the reaction mixture by filtration and was washed with ethanol containing 25% water (300mL). The filtrate and the washing solution were combined and the combined solution was concentrated under reduced pressure. The resultant pale brown crystal was suspended in tetrahydrofuran (100mL) and was collected by filtration. The collected crystal was washed with tetrahydrofuran and was dried under reduced pressure to give 34.1g of (3R, 4R)-3cyclopropylaminomethyl-4-methylpyrrolidine'trifluoroacetate as a white crystal. Example 1 Synthesis of (3R)-10-[(3S)-3-cyclopropylaminomethyl-lpyrrolidinyl]-9-fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7Hpyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid Process (A): [(3R) 9,10-Difluoro-3-fluoromethyl-2,3dihydro-7-oxo-7H-pyrido[l,2,3-d,e] [l,4]benzoxazine-6carboxylato-O6, OT]difluoroboron (51.0g), 3(R)- cyclopropylaminomethylpyrrolidine (24.7g), triethylamine (24.6mL) and dimethylsulfoxide (500mL) were mixed with one another and the mixture was stirred at 70°C for 1 hour. Subsequently, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified on a silica gel column (eluant = dichloromethane: methanol = I0:I). The eluates were combined and the combined solution was concentrated under reduced pressure. To the resulting residue, 80% ethanol (2500mL) and triethylamine (25.0mL) were added and the mixture was heat-refluxed for 2 hours while being stirred. Subsequently, the reaction mixture was left on an ice bath for 2 hours and the resulting crystal was collected by filtration. The collected crystal was washed with ethanol, was suspended in purified water (300ml), and was then collected by filtration. The collected crystal was dried under reduced pressure and was purified on a silica gel column (eluant = dichloromethane: methanol = I0:i). The eluates were combined and the combined solution was concentrated under reduced pressure. The resulting residue was dissolved in ethanol (2000mL) by heating and the solution was allowed to stand for 14 hours at room temperature. The resultant crystal was collected by filtration and the collected crystal was washed with ethanol and was dried under reduced pressure to give 27.7g of (3R)-10-[(3S)-3-cyclopropylaminomethyl-lpyrrolidinyl]-9-fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7Hpyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid as a yellow powder. Process B: To a dichloromethane solution (273mL) of bis(acetato-O) [(3R)-9,10-difluoro-3-fluoromethyl-2,3-dihydro7-oxo-7H-pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylato06,OT]boron (22.6g), (3R)-3-cyclopropylaminomethylpyrrolidine (8.41g) and triethylamine (7.59g) were added and the mixture was allowed to stand at room temperature for 13 hours. Subsequently, the reaction mixture was sequentially washed with water (200mL) and a saturated aqueous solution of sodium chloride (50ml), was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (dichloromethane: methanol = 15:1) to obtain a yellow amorphous product. To this product, a 5% aqueous solution of acetic acid (100mL) was added and the mixture was stirred at 80°C for 3 hours. Subsequently, the reaction mixture was washed with ethyl acetate (100mL). While the mixture was cooled on an ice bath, a Imol/L aqueous solution of sodium hydroxide was added to adjust the pH to 7.01 and the mixture was further stirred for 0.5 hours. The resultant crystal was collected by filtration, was washed with purified water (2 x 50mL), and was then dissolved in ethanol (1200mL) by heating. The solution was allowed to stand at room temperature for 12 hours. Subsequently, the resulting crystal was collected by filtration, followed by washing with ethanol and drying under reduced pressure, to give ll.2g of (3R)-10-[(3S)-3cyclopropylaminomethyl-l-pyrrolidinyl]-9-fluoro-3fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido[l,2,3- d,e] [l,4]benzoxazine-6-carboxylic acid as a yellow crystal. MS (EI)m/z: 419 (M÷). Elementary analysis (%): Calcd for C 21 H 23 F 2 N 3 0 4 : C 60.14, H 5.53, N 10.02; found: C 60.01, H 5.47, N 9.94. Example 2 Synthesis of (3R)-10-[(3R)-3-cyclopropylaminomethyl-lpyrrolidinyl ] -9-fluoro-3-fluorometh¥1-2,3-dihydro-7-oxo-7Hpyrido [l, 2, 3-d, e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example i, bis (acetato-O) [ (3R) -9, 10-difluoro-3-fluoromethyl-2,3-dihydro7-oxo-7H-pyrido [ i, 2,3-d, e] [I, 4 ] benzoxazine-6-carboxylato-O 6, 07] boron (982mg) was reacted with (3S)-3cyclopropylaminomethylpyrrolidine (335mg) to give 587mg of (3R) -i0- [ (3R) -3-cyclopropylaminomethyl-l-pyrrolidinyl ] -9fluoro-3fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido [ 1,2,3d,e] [l,4]benzoxazine-6-carboxylic acid as a yellow crystal. MS (FAB÷)m/z: 420 (MH÷). Elementary analysis (%): Calcd for C 21 H 23 F 2 N 3 0 4 "0.25H 2 0: C 59.50, H 5.59, N 9.91; found: C 59.68, H 5.47, N 9.97. Example 3 Synthesis of (3R)-10-[3-cycloprop laminomethyl-lpyrrolidinyl ] - 9fluoro-3fluoromethyl-2,3-dihydro7-oxo-7Hpyrido [l, 2, 3-d, e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example I, bis (acetato-O) [ (3R) -9, 10-difluoro-3-fluoromethyl-2,3-dihydro7-oxo-7H-pyrido [I, 2,3-d, e] [I, 4 ] benzoxazine-6-carboxylatoO6,OT]boron (513mg) was reacted with 3cyclopropylaminomethylpyrrolidine (185mg)to give 231mg of (3R) -i0- ( 3-cyclopropylaminomethyl-l-pyrrolidinyl ) - 9fluoro-3d,e] [l,4]benzoxazine-6-carboxylic acid as a yellow crystal. MS (FAB÷)m/z: 420 (MH+). Elementary analysis (%): Calcd for C 21 H 23 F 2 N 3 0 4 "0.25H 2 0: C 59.50, H 5.59, N 9.91: found: C 59.41, H 5.41, N 9.89. Example 4 Synthesis of (3S)-I0-[ 3S)-3-cyclopropylaminomethyl-lpyrrolidinyl]-9-fluoro-2,3-dihydro-3-methoxymethyl-7-oxo-7Hpyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example I, bis(acetato-O) [(3S)-9,10-difluoro-2,3-dihydro-3-methoxymethyl7-oxo-7H-pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylatoO6,O7]boron (790mg) was reacted with (3R)-3cyclopropylaminomethylpyrrolidine (303mg) to give 602mg of (3S)-10-[(3S)-3-cyclopropylaminomethyl-l-pyrrolidinyl]-9fluoro-2,3-dihydro-3-methoxymethyl-7-oxo-7H-pyrido[l,2,3d,e] [l,4]benzoxazine-6-carboxylic acid as a yellow crystal. MS (FAB÷) m/z: 432 (MH+). Elementary analysis (%): Calcd for C 22 H 26 FN 3 0 5 : C 61.24, H 6.07, N 9.74; found: C 61.01, H 6.04, N 9.73. Example Synthesis of (3S)-3-acetoxymethyl-10-[(3S)-3cyclopropylaminomethyl-l-pyrrolidinyl]-9-fluoro-2,3-dihydro-7oxo-7H-pyrido [l, 2, 3-d, e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example i, bis (acetato-O) [ (3S) -3-acetoxymethyl-9, 10-difluoro-2,3-dihydro7-oxo-7H-pyrido [I, 2,3-d, e] [i, 4 ] benzoxazine-6-carboxylatoO6, OV]boron(934mg) was reacted with (3R)-3cyclopropylaminomethylpyrrolidine(337mg)to give 612mg of (3S)- 3-acetoxymethyl-10- [ (3S) -3-cyclopropylaminomethyl-lpyrrolidinyl ] -9-fluoro-2,3-dihydro-7-oxo-7H-pyrido [ I, 2,3d,e] [l,4]benzoxazine-6-carboxylic acid as a yellow crystal. MS (FAB+) m/z: 460 (MH+). Elementary analysis (%): Calcd for C 23 H 26 FN 3 0 6 "H 2 0: C 57.85, H 5.91, N 8.80; found: C 57.94, H 5.83, N 8.89. Example 6 Synthesis of (3S)-10-[(3S)-3-cyclopropylaminomethyl-lpyrrolidinyl]-9-fluoro-2,3-dihydro-3-hydroxymethyl-7-oxo-7Hpyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid A Imol/L aqueous solution of sodium hydroxide (8.0mL) containing (3S)-3-acetoxymethyll0-[(3S)-3cyclopropylaminomethyl-l-pyrrolidinyl]-9-fluoro-2,3-dihydro-7 oxo-7H-pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid (368mg) was stirred at 50°C for 2 hours. While this mixture was cooled on an ice bath, imol/L hydrochloric acid was added to adjust the pH to 7.05 and the mixture was further stirred for 0.5 hours. The resultant crystal was collected by filtration, was washed with purified water, and was then dissolved in ethanol (50mL) by heating. The solution was allowed to stand at room temperature for 2 hours. Subsequently, the resulting crystal was collected by filtration, was washed ethanol, and was then dried under reduced pressure to give 251mg of (3S)-10-[(3S)-3-cyclopropylaminomethyl-lpyrrolidinyl]-9-fluoro-2,3-dihydro-3-hydroxymethyl-7-oxo-7Hpyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid as a yellow crystal. MS (FAB÷) m/z: 418 (MH÷). Elementary analysis (%): Calcd for C 21 H 24 FN 3 0 5 "0.5H 2 0: C 59.15, H 5.91, N 9.85; found: C 59.16, H 5.92, N 9.88. Example 7 Synthesis of 10-[(3S)-3-cyclopropylaminomethyl-lpyrrolidinyl]-9-fluoro-2,3-dihydro-3-methylene-7-oxo-7Hpyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid (3R)-10-[(3S)-3-Cyclopropylaminomethyl-l-pyrrolidinyl]-9fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido[l,2,3d,e] [l,4]benzoxazine-6-carboxylic acid (252mg) was suspended in ethanol (imL). To this suspension, a Imol/L aqueous solution of sodium hydroxide (6mL) was added and the mixture was stirred at room temperature for 2 hours. Subsequently, the reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in purified water (10ml). While this solution was cooled on an ice bath, imol/L hydrochloric acid was added to adjust the pH to 7.03 and the mixture was further stirred for 0.5 hours. The resultant crystal was collected by filtration to obtain 214mg of 10- [(3S)-cyclopropylmethylamino-l-pyrrolidinyl]-9-fluoro-2,3dihydro-3-methylene-7-oxo-7H-pyrido[l,2,3d,e] [l,4]benzoxazine-6-carboxylic acid as a yellow powder. MS (FAB÷)m/z: 400 (MH÷). Elementary analysis (%): Calcd for C 22 H 23 FN 3 0 4 "I.75H 2 0: C 58.53, H 5.96, N 9.75; found: C 58.62, H 5.79, N 9.76. Example 8 Synthesis of (3R)-I0-[ (3S)-cyclopropylaminomethyl-lpyrrolidinyl ] -3fluoromethyl-2,3-dihydro-7-oxo-7Hpyrido [l, 2, 3-d, e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example i, bis (acetato-O) [ (3R) -10-fluoro-3-fluoromethyl-2,3-dihydro-7oxo-7H-pyrido [I, 2,3-d, e] [I, 4 ] benzoxazine-6-carboxylato06, OT]boron (500mg) was reacted with (3R)-3cyclopropylaminomethylpyrrolidine (240mg) to give 335mg of (3R) -I0- [ ( 3S ) -3-cyclopropylaminomethyl-l-pyrrolidinyl ] -3fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido [ 1,2,3d,e] [l,4]benzoxazine-6-carboxylic acid as a yellow needleshaped product. Elementary analysis (%): Calcd for C 21 H 24 FN 3 0 4 : C 62.83, H 6.03, N 10.47; found: C 62.56, H 5.94, N 10.40. Example 9 Synthesis of (3S)-I0-[ (3S)-cyclopropylaminomethyl-lpyrrolidinyl ] -2, 3-dihydro-3-methyl-7-oxo-7H-pyrido [ I, 2,3d,e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example I, bis (acetato-O) [ ( 3S ) -I 0-fluoro-2,3-dihydro-3-methyl-7-oxo-THpyrido [i, 2, 3-d, e] [I, 4] benzoxazine-6-carboxylato-O 6, O 7] boron (1000mg) was reacted with (3R)-3cyclopropylaminomethylpyrrolidine (431mg) to give 335mg of (3S) -I0- [ (3S) -3-cyclopropylaminomethyl-l-pyrrolidinyl] -2,3dihydro-3-methyl-7-oxo-7H-pyrido [i, 2,3-d, e] [i, 4] benzoxazine-6carboxylic acid as a yellow needle-shaped product. MS (EI÷) m/z: 383 (M+). Elementary analysis (%): Calcd for C 21 H 25 N 3 0 4 : C 65.78, H 6.57, N 10.96; found: C; 65.58, H 6.61, N 10.91. Example i0 Synthesis of (3S)-10-(trans-3-cyclopropylaminomethyl-4-methyll-pyrrolidinyl)-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7Hpyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example I, bis(acetato-O) [(3S)-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo7H-pyrido [I, 2,3-d, e] [ i, 4 ] benzoxazine-6-carboxylato-O 6, O 7] boron (300mg) was reacted with trans-3-cyclopropylaminomethyl-4methylpyrrolidine (136mg) to give 166mg of (3S)-10-(trans-3cyclopropylaminomethyl4 -methyll-pyrrolidinyl ) -9-fluoro-2,3dihydro-3o-methyl-7-oxo-7H-pyrido [i, 2, 3-d, e] [I, 4 ] benzoxazine-6carboxylic acid as yellow crystal. MS (EI÷) m/z: 415 (M÷). Elementary analysis (%): Calcd for C 22 H 26 FN 3 0 4 "0.5H 2 0: C 62.25, H 6.41, N 9.90; found: C 62.30, H 6.17, N 10.06. Example Ii Synthesis of (3S)-10-[(3S,4R)-3-cyclopropylaminomethyl-4methyl-l-pyrrolidinyl ] -9-fluoro-2,3-dihydro-3-methyl-7-oxo-7Hpyrido [l, 2, 3-d, e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example I, bis (acetato-O) [ (3S) -9, 10-difluoro-2,3-dihydro-3-methyl-7-oxo7H-pyrido [I, 2, 3-d, e] [ i, 4 ] benzoxazine-6-carboxylato-O 6, O 7] boron (500mg) was reacted with (3R,4R)-3-cyclopropylamino-4methylpyrrolidine (226mg) to give 362mg of (3S)-10-[(3S,4R)-3cyclopropylaminomethyl4-methyl-l-pyrrolidinyl ] -9-fluoro-2,3dihydro-3-methyl-7-oxo-7H-pyrido [I, 2,3-d, e] [i, 4] benzoxazine-6carboxylic acid as a yellow crystal. MS (EI÷) m/z:415 (M÷) Elementary analysis (%): Calcd for C 22 H 26 FN 3 0 4 : C 63.60, H 6.31, Example 12 Synthesis of (3S)-10-[(3R,4S)-3-cyclopropylaminomethyl-4methyl-l-pyrrolidinyl ] - 9-fluoro-2,3-dihydro-3-methyl-7-oxo-7Hpyrido [l, 2, 3-d, e] [l,4]benzoxazine-6-carbox¥1ic acid In a similar manner to Process (B) in Example I, bis (acetato-O) [ (3S) -9, 10-difluoro-2, 3-dihydro-3-methyl-7-oxo7H-pyrido [i, 2, 3-d, e] [i, 4 ]benzoxazine-6-carboxylato-O 6, O 7] boron (500mg) was reacted with (3S,4S)-3-cyclopropylamino-4methylpyrrolidine (226mg) to give 276mg of (3S)-I0-[ (3R,4S)- cyclopropylaminomethyl4 -methyll-pyrrolidinyl ] -9-fluoro-2,3dihydro-3-methyl-7-oxo-7H-pyrido [I, 2,3-d, e] [I, 4 ] benzoxazine-6carboxylic acid as a pale yellow crystal. MS (EI÷) m/z: 415 (M÷). Elementary analysis (%): Calcd for C 22 H 26 FN 3 0 4 "0.5 H 2 0: C 62.25, H 6.41, N 9.90; found: C 62.23, H 6.06, N 9.92. Example 13 Synthesis of (3S) -I0- (cis-3-cyclopropylaminomethyl-4-methyl-lpyrrolidinyl ) - 9-fluoro-2,3-dihydro-3-methyl-7-oxo-7Hpyrido [l, 2, 3-d, e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example I, bis (acetato-O) [ (3S) -9, 10-difluoro-2, 3-dihydro-3-methyl-7-oxo7H-pyrido [I, 2, 3-d, e] [I, 4] benzoxazine-6-carboxylato-O 6, 07] boron (220mg) was reacted with cis-3-cyclopropylaminomethyl-4methylpyrrolidine (100mg) to give 109mg of (3S)-10-(cis-3cyclopropylaminomethyl-4-methyl-l-pyrrolidinyl ) - 9fluoro-2,3dihydro-3-methyl-7-oxo-7H-pyrido [ 1,2, 3-d, e ] [ 1, 4 ] benzoxazine6- carboxylic acid as a yellow crystal. MS (EI÷) m/z: 415 (M+). Elementary analysis (%): Calcd for C 22 H 26 FN 3 0 4 "H 2 0: C 60.96, H 6.51, N 9.69; found: C 61.27, H 6.69, N 9.52. Example 14 Synthesis of (3S)-10-[(3S,4S)-3-cyclopropylaminomethyl-4methyl-l-pyrrolidinyl ] -9-fluoro-2,3-dihydro-3-methyl-7-oxo-7Hpyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example i, bis (acetato-O) [ (3S) -9, 10-difluoro-2,3-dihydro-3-methyl-7-oxo7H-pyrido [I, 2,3-d, e] [i, 4 ] benzoxazine-6-carboxylato-O 6, O7]boron (1000mg) was reacted with (3R, 4S)-cyclopropylamino-4methylpyrrolidine (452mg) to give 474mg of (3S)-10-[(3S,4S)-3cyclopropylaminomethyl-4-methyll-pyrrolidinyl ] -9-fluoro-2,3dihydro-3-methyl-7-oxo-7H-pyrido [I, 2,3-d, e] [I, 4 ] benzoxazine-6carboxylic acid as a yellow crystal. MS (EI÷) m/z: 415 (M+). Elementary analysis (%): Calcd for C 22 H 26 FN 3 0 4 "0.25H 2 0: C 62.92, H 6.36, N I0.01; found: C 62.69, H 6.52, N 9.98. Example Synthesis of (3S)-i0-[ (3R,4R)-3-cyclopropylaminomethyl-4methyl-l-pyrrolidinyl ] -9-fluoro-2,3-dihydro-3-methyl-7-oxo-7Hpyrido [l, 2, 3-d, e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example i, bis (acetato-O) [ (3S) -9, 10-difluoro-2,3-dihydro-3-methyl-7-oxo7H-pyrido [I, 2,3-d, e] [i, 4 ] benzoxazine-6-carboxylato-O 6, 07] boron (250mg) was reacted with (3S,4R)-3-cyclopropylamino-4methylpyrrolidine (ll3mg) to give 33mg of (3S)-10-[(3R,4R)- cyclopropylaminomethyl4 -methyl -I -pyrrolidinyl ] - 9fluoro-2,3dihydro-3-methyl-7-oxo-7H-pyrido [i, 2,3-d, e] [ i, 4 ] benzoxazine-6carboxylic acid as a pale yellow crystal. MS (EI+) m/z: 415 (M÷). Elementary analysis (%): Calcd for C 22 H 26 FN 3 0 4 "0.5H 2 0: C 62.25, H 6.41, N 9.90; found: C 61.98, H 6.57, N 9.91. Example 16 Synthesis of (3R) -I 0- (trans-3-cyclopropylaminomethyl-4-methyll-pyrrolidinyl ) - 9fluoro-3fluoromethyl-2,3-dihydro-7-oxo-7Hpyrido [l, 2, 3-d, e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example i, bis (acetato-O) [ (3R) -9, 10-difluoro-3-fluoromethyl-2,3-dihydro7-oxo-7H-pyrido [ i, 2,3-d, e] [i, 4 ] benzoxazine-6-carboxylatoO6,OT]boron (300mg) was reacted with trans-3cyclopropylaminomethyl-4-methylpyrrolidine (130mg) to give ll0mg of (3R)-10-(trans-3-cyclopropylaminomethyl-4-methyl-lpyrrolidinyl) -9-fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7Hpyrido [l, 2, 3-d, e] [l, 4] benzoxazine-6-carboxylic acid. MS (EI÷) m/z: 433 (M+). Elementary analysis (%): Calcd for C 22 H 2 sF 2 N 3 0 4 : C 60.96, H 5.81, N 9.69; found: C 60.81, H 5.85, N 9.66. Example 17 Synthesis of (3R)-10-[(3S,4R)-3-cyclopropylaminomethyl-4methyl-l-pyrrolidinyl] -9-fluoro-3-fluoromethyl-2,3-dihydro-7oxo-7H-pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example i, bis (acetato-O) [ (3R) -9, 10-difluoro-3-fluoromethyl-2,3-dihydro7-oxo-7H-pyrido [I, 2,3-d, e] [I, 4 ] benzoxazine-6-carboxylatoO6, O7]boron (1000mg) was reacted with (3R, 4R)-cyclopropylamino4-methylpyrrolidine (397mg) to give 620mg of (3R)-I0-[(3S,4R)- 3 - cycl opr opyl ami nomethyl - 4 -met hyl - 1 -pyr rol idinyl ] - 9f luoro3 - fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido [ 1,2,3d,e] [l,4]benzoxazine-6-carboxylic acid as a yellow crystal. MS (EI÷) m/z: 433 (M÷). Elementary analysis (%): Calcd for C 22 H 25 F 2 N 3 0 4 : C 60.96, H 5.81, N 9.69; found: C 60.81, H 5.86, N 9.63. Example 18 Synthesis of (3R)-10-[(3S,4S)-3-cyclopropylaminomethyl-4methyl-l-pyrrolidinyl]-9-fluoro-3-fluoromethyl-2,3-dihydro-7oxo-7H-pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example I, bis (acetato-O) [ (3R) -9, 10-difluoro-3-fluoromethyl-2,3-dihydro7-oxo-7H-pyrido [i, 2,3-d, e] [I, 4 ] benzoxazine-6-carboxylato06,OT]boron (500mg) was reacted with (3R, 4R)-cyclopropylamino4-methylpyrrolidine (199mg) to give 422mg of (3R)-I0-[(3S,4S)- 3cyc 1 opropyl aminomethyl4 -methyl - 1 -pyr ro i idinyl ] - 9f i uoro3- fluoromethyl-2,3-dihydro-7 -oxo-7H-pyrido [ 1,2, 3d,e] [l,4]benzoxazine-6-carboxylic acid as a yellow crystal. MS (EI÷) m/z: 433 (M÷). Elementary analysis (%): Calcd for C 22 H 25 F 2 N 3 0 4 : C 60.96, H 5.81, N 9.69; found: C 60.79, H 5.91, N 9.77. Example 19 Synthesis of (3S)-10-(trans-3-cyclopropylaminomethyl-4trifluoromethyl-l-pyrrolidinyl)-9-fluoro-2,3-dihydro-3-methyl7-oxo-7H-pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example I, bis(acetato-O) [(3S)-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo- 7H-pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylato-O6,O7]boron (300mg) was reacted with trans-3-cyclopropylaminomethyl-4trifluoromethylpyrrolidine (198mg) to give 87mg of (3S)-10- (trans-3-cyclopropylaminomethyl-4-trifluoromethyl-lpyrrolidinyl)-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H- pyrido[l,2,3-d,e] [l,4]benzoxazine-6-carboxylic acid. Elementary analysis (%): Calcd for C 22 H 23 F 4 N 3 0 4 : C 56.29, H 4.94, N 8.95; found: C 55.97, H 4.84, N 9.00. Example Synthesis of (3R)-10-[(3S,4S)-3-cyclopropylaminomethyl-4fluoro-l-pyrrolidinyl ] -9-fluoro-3-fluoromethyl-2,3-dihydro-7oxo-7H-pyrido[l,2,3-d.e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example I, bis (acetato-O) [ (3R) -9, 10-difluoro-3-fluoromethyl-2,3-dihydro7-oxo-7H-pyrido [I, 2,3-d, e] [I, 4 ] benzoxazine-6-carboxylatoO6,O7]boron (500mg) was reacted with (3R,4S)-3cyclopropylaminomethyl-4-fluoropyrrolidine (204mg) to give 387mg of (3R)-I0-[ (3S,4S)-3-cyclopropylaminomethyl-4-fluoro-lpyrrolidinyl ] - 9fluoro-3 - f luoromethy1-2,3 -dihydro7 -oxo7 Hpyrido[l,2,3-d.e] [l,4]benzoxazine-6-carboxylic acid as a pale yellow crystal. MS (FAB÷) :m/z=438 (MH+). Elementary analysis (%): Calcd for C 21 H 22 F 3 N 3 0 4 : C 57.66, H 5.07, N 9.61; found: C 57.47, H 5.07, N 9.57. Example 21 Synthesis of (3S)-10-[(3S,4S)-3-cyclopropylamino-4-fluoro-lpyrrolidinyl]-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7Hpyrido[l,2,3-d.e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example i, bis (acetato-O) [ (3S) -9, 10-difluoro-2,3-dihydro-3-methyl-7-oxo7H-pyrido [I, 2,3-d, e] [i, 4 ] benzoxazine-6-carboxylato-O 6, O 7] boron (64.6mg) was reacted with (3R,4S)-3-cyclopropylaminomethyl-4fluoropyrrolidine (25.0mg) to give 18.5mg of (3R)-10-[(3S,4S)- 3-cyclopropylamino-4-fluoro-l-pyrrolidinyl ] -9fluoro-2,3dihydro-3-methyl-7-oxo-7H-pyrido [I, 2, 3-d. e] [I, 4]benzoxazine-6carboxylic acid as a yellow powder. MS (FAB÷) m/z=420 (MH÷). HRMS (FAB+): Calcd for C 21 H 24 F 2 N 3 0 4 : 420.1735; found: 420.1747. Example 22 Synthesis of (3R)-10-[(3S,4S)-3-[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl-4-fluoromethyl-l-pyrrolidine]-9fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido[l,2,3d.e] [l,4]benzoxazine-6-carboxylic acid Bis(acetato-O) [ (3R)-9,10-difluoro-3-fluoromethyl-2,3dihydro-7-oxo-7H-pyrido [I, 2,3-d, e] [i, 4 ] benzoxazine-6carboxylato-O6,OT]boron (912mg), (3R,4S)-3-[ (N-tertbutoxycarbonyl-N-cyclopropyl)amino]methyl-4fluoromethylpyrrolidine (640mg), triethylamine (0.33mL) and acetonitrile (17mL) were mixed with one another and the mixture was stirred at 60°C for 90min. Subsequently, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified on a silica gel column (eluant = ethyl acetate: methanol = 20:1). To the eluate, a 5% aqueous solution of acetic acid (17mL) and ethanol (10mL) were added and the mixture was stirred at 80°C for 2 hours. The mixture was allowed to cool and the resulting crystal was collected by filtration, was washed with a mixture of water and ethanol, and was then dried under reduced pressure to give 915mg of (3R)-10-[(3S,4S)-3-[(N-tert-butoxycarbonyl-Ncyclopropyl)amino]methyl-4-fluoromethyl-l-pyrrolidine]-9fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido [1,2,3d.e] [l,4]benzoxazine-6-carboxylic acid as a yellow powder. MS (EI) m/z = 551 (M+). Elementary analysis (%): Calcd for C 27 H 32 F 3 N 3 0 6 "0.5H 2 0: C 57.85, H 5.93, N 7.50; found: C 57.90, H 5.80, N 7.49. Example 23 Synthesis of (3R)-10-[(3S,4S)-3-cyclopropyl]amino]methyl-4fluoromethyl-l-pyrrolidinyl]-9-fluoro-3-fluoromethyl-2,3dihydro-7-oxo-7H-pyrido[l,2,3-d.e] [l,4]benzoxazine-6carboxylic acid hydrochloride (3R)-10-[(3S,4S)-3-[(N-tert-Butoxycarbonyl-Ncyclopropyl)amino]methyl-4-fluoromethyl-l-pyrrolidine]-9fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido[l,2,3d.e] [l,4]benzoxazine-6-carboxylic acid (860mg) was dissolved in ethanol (9mL) saturated with hydrogen chloride. The mixture was stirred at room temperature for 1 hour and was subsequently concentrated under reduced pressure. To the resulting residue, ethanol (50mL) was added and the mixture was concentrated under reduced pressure. After repeating the ethanol addition and concentration once, ethanol (50mL) was added to the resultant residue, and the mixture was heated to 70°C and was then allowed to stand at room temperature for 1 hour. The resulting crystal was collected by filtration, followed by washing with ethanol and drying under reduced pressure, to give 762mg of (3R)-10-[(3S,4S)-3cyclopropyl]amino]methyl-4-fluoromethyl-l-pyrrolidinyl]-9fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido[l,2,3d.e] [l,4]benzoxazine-6-carboxylic acid hydrochloride as a yellow crystal. MS (FAB÷): m/z=452 (MH+). Elementary analysis (%): Caicd for C 22 H 24 F 3 N 3 0 4 "HCI'H 2 0"0.5C 2 H 5 OH: C 52.23, H 5.72, N 7.94; found: C 52.17, H 5.38, N 8.20. Example 24 Synthesis of (3R)-10-[(3S,4R)-3-cyclopropylaminomethyl-4fluoro-l-pyrrolidinyl ] -9fluoro-3fluoromethyl-2, 3-dihydro-7 - oxo-7H-pyrido[l,2,3-d.e] [l,4]benzoxazine-6-carboxylic acid In a similar manner to Process (B) in Example I, bis (acetato-O) [ (3R) -9, 10-difluoro-3-fluoromethyl-2,3-dihydro7-oxo-7H-pyrido [ i, 2,3-d, e] [i, 4 ] benzoxazine-6-carboxylatoO6, OT]boron (100mg) was reacted with (3R,4R)-3cyclopropylaminomethyl-4-fluoropyrrolidine (40.6mg) to give 71.0mg of (3R)-10-[(3S,4R)-3-cyclopropylaminomethyl-4-fluorol-pyrrolidinyl ] - 9fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7Hpyrido[l,2,3-d.e] [l,4]benzoxazine-6-carboxylic acid as a pale yellow crystal. MS (FAB+): m/z=438 (MH÷). Elementary analysis (%): Calcd for C 21 H 22 F 3 N 3 0 4 : C 57.66, H 5.07, N 9.61; found: C 57.50, H 5.18, N 9.22. Example Synthesis of (3R)-10-[(3S,4S)-3-cyclopropylaminomethyl-4fluoro-l-pyrrolidinyl]-9-fluoro-3-fluoromethyl-2,3-dihydro-7oxo-7H-pyrido[l,2,3-d.e] [l,4]benzoxazine-6-carboxylic acid methanesulfonate (3R)-10-[(3S,4S)-3-Cyclopropylaminomethyl-4-fluoro-lpyrrolidinyl]-9-fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7Hpyrido[l,2,3-d.e] [l,4]benzoxazine-6-carboxylic acid (50.0mg) was suspended in ethanol (2mL). To this suspension, methanesulfonic acid (15.0 L) was added and the mixture was stirred at room temperature for 1 hour. The resulting crystal was collected by filtration, was washed with ethanol, and was then dried under reduced pressure to give 50.4mg of (3R)-10- [(3S,4S)-3-cyclopropylaminomethyl-4-fluoro-l-pyrrolidinyl]-9fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido[l,2,3d.e] [l,4]benzoxazine-6-carboxylic acid methanesulfonate as a pale yellow crystal. MS (FAB+): m/z = 438 (MH+). Elementary analysis (%): Calcd for C 21 H 22 F 3 N 3 0 4 "CH 3 SO 3 H'0.25H 2 0: 49.11, H 4.96, N 7.81; found: C 49.18, H 4.86, N 7.42. Example 26 Synthesis of (3R)-10-[(3S,4S)-3-cYclopropylaminomethyl-4fluoro-l-pyrrolidinyl]-9-fluoro-3-fluoromethyl-2,3-dihydro-7oxo-7H-pyrido[l,2,3-d.e] [l,4]benzoxazine-6-carboxylic acid hydrochloride (3R)-10-[(3S,4S)-3-Cyclopropylaminomethyl-4-fluoro-lpyrrolidinyl]-9-fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7Hpyrido[l,2,3-d.e] [l,4]benzoxazine-6-carboxylic acid (50.0mg) was suspended in ethanol (2mL). To this suspension, ethanol (60.0 L) saturated with hydrogen chloride was added and the mixture was stirred at room temperature for 1 hour. The resulting crystal was collected by filtration, was washed with ethanol, and was then dried under reduced pressure to give 52.9mg of (3R)-10-[(3S,4S)-3-cyclopropylaminomethyl-4-fluorol-pyrrolidinyl]-9-fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7Hpyrido[l,2,3-d.e] [l,4]benzoxazine-6-carboxylic acid hydrochloride as a pale yellow crystal. MS (FAB÷) : m/z=438 (MH÷) . Elementary analysis (%): Calcd for C 21 H 22 F 3 N 3 0 4 "HCI'0.25H 2 0: C (Antibacterial activity) Test Example i: in vitro antibacterial activity The in vitro antibacterial activity (as measured by the minimum inhibitory concentration (MIC)) was determined for each of the compounds of the present invention by the agar dilution method according to NCCLS (National Committee for Clinical Laboratory Standard (1997), Methods for Dilution Antibacterial Susceptibility Tests for Bacteria that grow Aerobically-Forth Edition: Approved Standard m7-A4. NCCLS, Villanova, Pa.), which involved the use of Muller-Hinton agar medium. For pneumococci and enterococci, MIC was determined by using Muller-Hinton agar medium containing 5% defibrinated equine blood. The results are shown in Table 1 below. Table 1 :in vitro antibacterial activity Strain MIC (mg/mL) Example 1 Example 2 Example 4 Example 5 Example 6 S. aureus Smith 0.016 0.031 0.031 0.25 0.25 S. aureus MR5867 0.016 0.016 0.031 0.25 0.25 S. aureus MS16401 0.125 0.25 0.5 4 4 S. pneumoniae Type III 0.032 0.125 0.125 0.125 0.125 E. faecalis IID682 0.063 0.25 0.25 0.25 0.25 Strain MIC (mg/mL) Example Example Example Example Example 7 10 11 12 13 S. aureus Smith<0.008 0.016 0.008 0.016 0.008 S. aureus MR5867<0.008 0.016 0.008 0.016 0.008 S. aureus MS16401 0.063 0.063 0.031 0.063 0.031 S. pneumoniae Type III 0.016 0.031 0.016 0.063 0.031 E. faecalis IID682 0.125 0.125 0.063 0.25 0.125 Strain MIC (mg/mL) Example Example Example Example Example 14 15 16 17 18 S. aureus Smith 0.008 0.031 0.016 0.008 0.008 S. aureus MR5867 0.008 0.031 0.016 0.008 0.016 S. aureus MS16401 0.031 0.063 0.063 0.063 0.063 S. pneumoniae Type III_<0.008 0.063 0.032 0.016 0.016 E. faecalis IID682 0.063 0.125 0.063 0.063 0.063 Strain MIC (mg/mL) Example Example Example Ciprofloxacin 19 20 21 S. aureus Smith 0.016 0.008 0.016 0.25 S. aureus MR5867 0.016 0.016 0.016 0.25 S. aureus MS16401 0.125 0.063 0.031 8 S. pneumoniae Type III 0.125 0.016 0.016 0.5 E. faecalis IID682 0.25 0.063 0.063 0.5 S. aureus MR5867: methicillin-resistant S. aureus S. aureus MS16401: quinolone-resistant S. aureus INDUSTRIAL APPLICABILITY The novel 10-(3-cyclopropylaminomethyl-lpyrrolidinyl)pyridobenzoxazine carboxylic acid derivatives, salts and hydrates thereof, which are compounds of the present invention, are not only safe and exhibit strong antibacterial activities, but they are also effective against drug-resistant bacteria that are less susceptible to conventional antibacterial agents. It is to be understood that, if any prior art publication is referred to herein, such reference does not constitute an admission that the publication forms a part of the common general knowledge in the art, in Australia or any other country. In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention.