PROCESS FOR PREPARATION OF BASIC DERIVATIVES OF BETA-TIENILO

NO DRAWINGS

(21) Application No. 27855/70 (22) Filed 9 June 1970

(31) Convention Application No. A 5860 (32) Filed 19 June 1969 in

(33) Austria (ΟΕ)

(44) Complete Specification published 18 April 1973

(51) International Classification C07D 63/12 Α61Κ 27/00

(52) Index at acceptance

C2C 174-271-276 200 215 220 226 22Υ 246 247 254

25Υ 29Χ 29Υ 30Υ 311 313 31Υ 322 323 32Υ

338 351 355 360 362 363 364 365 36Υ 43Χ 509

50Υ 618 620 623 633 650 652 662 675 682 694

697 699 779 790 79Υ LF LJ LL LM ΝΜ

(54) BASIC ,/3-THIENYL DERIVATIVES

(71) We, DEUTSCHE GOLD- UND

SILBER - SCHEIDEANSTALT vormals

Roessler, a body corporate organised under

the laws of Germany, of 9, Weissfrauenstrasse,

Frankfurt/Main, Germany, do hereby declare

the invention, for which we pray that a patent

may be granted to us, and the method by

which it is to be performed, to be particu-

larly described in and by the following state-

ment: -

This invention relates to basic ,6-thienyl

derivatives which have been found to be phar-

macorogically active and in particular to

peripheral and cerebral blood flow.

The compounds according to the invention

correspond to the general formula

in which the thienyl radical can be substituted

one or more times by lower molecular weight

alkyl radicals; the bridge member 5 A-Β-

has the structure

; C(OH)-QTLH-

or the structure

- A^C/R¹)-;

R1^, R², R³ and R⁴, which may be the same

or different, each represent a hydrogen atom

or lower molecular weight alkyl group; R⁵

represents a hydrogen atom or a hydroxyl

group; R“ and R⁷, which may be the same or

different,, each represent a hydrogen or a halo-

gen atom, a hydroxyl group, a lower mole-

cular weight alkyl group, a lower molecular

[Price 25p] . ... .

weight halogeno alkyl group or a lower molecular weight alkoxy group; and R⁸ and R⁹, which may be the same or different, each represent a hydrogen atom, a hydroxyl group, a lower molecular weight alkyl group or a lower molecular weight alkoxy group, their optically active and diastereomeric forms and their acid addition salts.

The lower molecular weight alkyl, halogenoalkyl and alkoxy groups are of the kind containing from 1 to 6 carbon atoms. One example of a halogenoalkyl group is the trifluoromethyl group.

Examples of compounds according to the invention corresponding to formula I are given in the following table.

In this table and in the following examples the compounds are named as derived from' NH₃ and the carbon atom of the group >A--Β-■ carrying the thienyl group and the phenyl group is numbered 1.

TABLE

[1 - thienyl - (3) - 1 - p - isopropyl phenyl - 1 - hydroxypropyl - (3)] - [1 phenyl-1 -hy droxypropyl-(2)] -amine ;

[1 - thienyl - (3) - 1 - ρ - isopropyl -

phenyl - propen - (1) - yl - (3)] - [1 phenyl-l-hydroxypropyl-(2)] -amine;

[1 - thienyl - (3) - 1 - m - methoxy -

phenyl - 1 - hydroxypropyl - (3)] - [1 phenyl-l-hydroxypropyl-(2)]-amine;

[1 - thienyl - (3) - 1 - m - methoxy -

phenyl - propen - (1) - yl - (3)] - [1 phenyl-l-hydroxypropyl-(2)]-amine;

[1 - thienyl - (3) - 1 - τη,ρ - dimethyl -

phenyl - 1 - hydroxypropyl - (3)] - [1 phenyl-l-hydrovxypropyl-(2)]-amine;

[1 - thienyl - (3) - 1 - ηΐ,ρ - dimethyl -

phenyl - propen - (1) - yl - (3)] - [1 phenyl-1 -hydroxypropyl-(2)] -amine;

[ 1 - thienyl - (3) - 1 - phenyl - 1 - hyd -

roxy - 2 - methylpropyl - (3)] - [1 - phenyl ? 1-hydroxypropyl-(2)] -amine;

[1 - thienyl - (3) - 1 - phenyl - 2 - methyl propen - (1) - yl - (3)] - [1 - phenyl - 1 hydroxypropyl-(2)]-amine ;

[1 - thienyl - (3) - 1 - phenyl - 1 - hyd 5 roxypropyl - (3)] - [1 - phenyl - 1 - hyd. roxypropyl-(2)] -methylamine ;

[1 - thienyl - (3) - 1 - phenyl - propen (1) - yl - (3)]. - [1 - phenyl - 1 - hydroxy propyl-(2)] -methylamine ;

[1 - thienyl - (3) - 1 - phenyl - 1 - hyd -

roxypropyl - (3)] - [1 - ρ - chlorophenyl - 2 methypropyI-(2)] -amine;

fl - thienyl - (3) - 1 - phenyl - propen -

1 - yl - (3)] - [1 - ρ - chlorophenyl - 2 methylpropyl-(2)] -amine;

[1 - thienyl - (3) - 1 - phenyl - 1 - hyd -

roxypropyl - (3)] - (2 - ρ - tert. - butyl phenyl-2-hydroxyethyl)-amine;

[1 - thienyl - (3) - 1 - phenyl - propen -

(i) _ yl _ (3)] - (2-ρ- tert, - butylphenyl - 2 hy droxyethyl)-amine ;

[1 - thienyl - (3) - 1 - phenyl - 1· - hyd -

roxypropyl - (3)] (2 - ρ - fluorophenyl - 2 hydroxyethyl)-amihe;

fl - thienyl - (3) - 1 - phenyl - propen -

(1) - yl - (3)] - 2 - ρ - fluorophenyl - 2 hydroxyethyI)-amine;

[1 - thienyl - (3) - 1 - phenyl - 1 - hyd -

roxypropyl - (3)] - (2 - ρ - chlorophenyl - 2 hydroxyethyl)-amine;

[1 - thienyl - (3) - 1 - phenyl - propen -

(1) - yl - (3)] - (2 - ρ - chlorophenyl - 2 hydroxyethyl)-amine;

[1 - thienyl - (3) - 1 - phenyl - 1 - hyd -

roxypropyl - (3)] - (2 - m - trifluoromethyl phenyl-2-hydroxyethyl)-amine;

fl - thienyl - (3) - 1 - phenyl - propen -

(1) - yl - (3)] - (2 - m - trifluoromethyl phenyl-2-hydroxyethyI)-atnine;

[1 - thienyl - (3) - 1 - phenyl - 1 - hyd -

roxypropyl - (3)] - [2 - (2,5 - dimethyl phenyl)-2-hydroxyethyl]-amine;

[1 - thienyl - (3) - 1 - phenyl - propen (1) - yl - (3)] - [2 - (2,5 - dimethylphenyl) 2-hydroxyethyl] -amine;

fl - thienyl - (3) - 1 - phenyl - 1 - hyd roxypropyl - (3)] - (2 - ρ - methoxyphenyl 2-hy droxyethyl)-amine ;

[1 - thienyl - (3) - 1 - phenyl - 1 - hyd -

roxypropyl - (3)] - (2 - ρ - hydroxyphenyl 2-dihydroxyethyl)-methylamine;

[1 - thienyl - (3) - 1 - phenyl - 1 - hyd -

roxypropyl - (3)] - [I - ρ - hydroxyphenyl l-hydroxypropyl-(2)]-amine.

The compounds according to the invention in which >A-Β- is

>C(OH)-CTR¹)H-

can be prepared by reacting a compound cor responding to the general formula

f R^e X-C0-CH-CH₂-N~C CH-X

R^ftfi

in which X’ represents a 3-thienyl radical optionally substituted by one or more lower molecular weight alkyl groups, with a corresponding phenyl metal compound or by reacting a compound, of formula. II in which X 65 represents die group

with a. corresponding thienyl metal compound the phenyl metal .compound has the formula

and the thienyl metal compound has the formula

where Μ is an alkali metal atom or MgHal where-Hal is -Cl, -Br or -I, Compounds 75 of general forumla I in which 5 A-Β- is >C(OH)-CH(R³}-,

may be converted into the corresponding imsaturated compounds in which > A-Β- is

>C-Qll¹)- 80

by the action of a dehydrating agent. The basic compounds obtained may optionally be converted into their add addition salts.

The. process in which a ketone of general formula II Is reacted with an organometallic 85 compound, preferably with a thienyl lithium or thienyl Grignard compound or with phenyl lithium or-a phenyl Grignard compound, is best carried out at a temperature in the range from -40. to + 100°C. Examples of suitable 90 solvents for this reaction indude dialkyl ethers, tetrahydrofuran, hydrocarbons and benzene.

Only 1 mol of organometallic compound is required for the actual reaction, although a 95 suitable excess is always necessary in cases where the compound II Used contains an active hydrogen atom e.g. as in an amino group or a hydroxyl group. Generally, however, it is advisable in many cases to employ 100 an excess of organometallic compound because it is possible in this way to obtain better yields.

The elimination of water from compounds in which A-Β- is

>C(OH)-℮Η(Β¹)- 105 is best carried out at devated temperatures,

for example at a temperature in the range from 20 to. 150^QC. It is preferred to use solvents such as glacial acetic acid, benzene or dioxan for this reaction..

Examples of suitable dehydrating agents include mineral adds such as sulphuric add and the hydrohalic acids; organic acids such as oxalic acid and formic acid; zinc chloride, tin chloride, boron trifluoride; potassium hydrogen sulphate; aluminium chloride; phosphorus pentoxide; aluminium oxide; acid chlorides; and red. phosphorus+iodine in the presence of water.

Any alkoxy groups present may optionally be split up into hydroxyl groups during dehydration. More precisely, this is governed by the dehydrating agent used and also by the conditions mider which the dehydrating reaction is carried out.

Those compounds, which contain asymmetric carbon atoms and¹, which usually accumulate in the form of racemates, can be split up into the optically active isomers or stercoisomeric forms, for example by means of reaction with an. optically active acid. It is also possible, however, to employ optically active or even stereoisomeric starting materials from the outlet, in which case a corresponding pure optically active form or diastereomeric configuration is obtained as the end product.

Suitable anions for the salts include the therapeutically usable acid radicals of the kind normally used for this purpose.

The compounds according to the invention are pharmacologically active and increase above all peripheral and cerebral blood flow. They are therefore suitable for increasing the flow of blood both through the brain and through the muscles.

Accordingly, the compounds according to the invention are suitable for the preparation of pharmaceutical compositions and preparations. The pharmaceutical compositions or medicaments contain, as active ingredient, one or more of the compounds according, to the invention, optionally in admixture with other pharmacologically active substances. The medicaments may be prepared using conventional pharmaceutical excipients and additives. The medicaments may be administered enterally, parenterally, orally, perlingually or in the form of sprays.

The dose for humans is usually between 1 and 100 mg of active ingredient once or several times a day. It can be administered in the form of tablets, capsules, pills, lozenges, suppositories, liquids or aerosols. Examples of suitable liquids include oily or aqueous solutions or suspensions, emulsions, and injectable aqueous or oily solutions ort:suspensions. Thus the present invention also:, provides a pharmaceutical composition- containing at least one compound according to the invention together with at least one other pharmaceutically active substance and/or at least one pharmaceutical excipient.

The invention, is illustrated by the following: Examples:-■

Ζ - [1 - Thienyl - (3) - 1 - phenyl - 1 -

hydroxy propyl - (3)] - [1 - phenyl - 1 hydroxypropyl-(2)] -amine

τ

℮Η(οπ:-0

^Ns/ CH-₂-fcH-2-WT-s-CH

ctt₃

A Grignard compound is. prepared, from 12.1 g (0.5 mol) of magnesium chips and 78.5 g (0.5 mol) of bromobenzene in 150 ml of absolute ether. A suspension of 32.5 g (0.1 mol) of I - β - [1 - phenyl - 1 - hydroxy propyl - (2) - amino] - propiothienenone - (3).

HC1 in 200 ml of absolute benzene is then added to this solution which is kept boiling for 2 hours. It is then decomposed with a solution of 25 mg of ammonium chloride in 250 ml of 10% ammonia, the organic phase is separated off, dried with potassium carbonate and the solvent distilled off. The residual base is dissolved in 200 ml of ether and neutralised with 10% isopropanolic HC1, resulting in precipitation of the HQ salt which is recrystallised from water. Yield 17 g., m,p.

214-215°C.

The I - β - [1 - phenyl - 1 - hydroxy propyl - (2) - amino] - propiothienone - (3) hydrochloride is prepared as follows:

31.5 g (0.25 mol) of 3-acetyl-thiophene, 7.5 g of paraformaldehyde and 47 g (0.25 mol) of Z-norephedrin hydrochloride are boiled under reflux for 3 hours in 100 ml of isopropanol, another 3.8 g of paraformaldehyde being added after 1 hour. The HQ salt is precipitated on cooling and is recrystallised from ethanol. Yield 52 g, m.p. 195-196°C.

Ζ - {1 - [2,5 - Dimethyl - thienyl - (3)] - 1 -

phenyl - 1 - hydroxypropyl - (3)} - [1 phenyl- l-hydroxypropyI-(2)] -amine

ch₃-

/ V

ch₃

OH

| O CH(OH)-^ ^ CH_s-CHg-NH-CH

CH₃

A Grignard compound is prepared from 12.1 g (0.5 mol) of magnesium, chips and 78.5 (0.5 mol) of bromobenzene in 150 ml of absolute ether, reacted as in Example 1 with 35.4 g (0.1 mol) of Z-,S-[ 1-phcnyl-1-hydroxypropyl - (2) - amincr] - 2,5 - di methyl - propiothienone - (3) hydrochloride in 200 ml of absolute benzene and the reaction product worked up. The HQ salt is recrystallised from 20% ethanol and then from methyl ethyl ketone. Yield 12 g., m.p. 192-193°C.

The 1 - β - [1 - phenyl - 1 - hydroxy propyl - (2) - amino] - 2,5 - dimethyl - pro piothienone - (3) hydrochloride is prepared as follows:

115.5 g (0.75 mol) of 3-acetyl-2,5-dimethylthiophene, 22.5 g of paraformaldehyde and 140.7 g (0.75 mol) of Z-norephedrin hydrochloride are boiled under reflux for 3 hours in 500 ml of isopropanol, another 11.3 g of paraformaldehyde being added after 1 hour.

The HQ salt is precipitated on cooling and is reciystallised from ethanol. Yield 161 g., m.p. 207-208°C.

HQ gas is introduced into a suspension of 16 g (0.04 mol) of Z-[l-thienyl-(3)-l-phenyl-1 - hydroxypropyl - (3) - [1 - phenyl - 1 hydroxypropyl - (2)] - amine hydrochloride in 150 ml of glacial acetic acid, as a result of which the starting material initially enters into solution and the HQ salt of the reaction product is precipitated after some 20 minutes.

The HQ salt is reciystallised from 20% ethanol. Yield 10 g., m.p. 228-230°C.

A Grignard compound is prepared from 12.1' g (0.5 mol) of magnesium and 78.5 g (0.5 mol) of bromobenzene in 150 ml of absolute ether, reacted as in Example 1 with 33.9 g (0.1 mol) of I - a - methyl - β - [1 phenyl - 1 - hydroxypropyl - (2) - amino] propiothienone-(3) hydrochloride (m.p. 188^;-190°C, prepared by reacting 3-propionyl-thiophene with paraformaldehyde and Z-norephedrin in hydrochloride in isopropanol at boiling temperature) and the reaction product 50 similarly worked up. The base solidifies when treated with ether (m.p. 62-68°C). It is dissolved in 100 ml of acetone and neutralised with isopropanolic HQ (7Ν). The HQ salt is reciystallised from acetone, m.p. 184- 55 185°C. Yield 8 g.

CHg- CHg-ΝΗ-CH

:ch₃

A Grignard compound was prepared from 12.1 g (0.5 mol of magnesium and 99.5 g (0.5 mol) of 4-bromocumene in 150 ml of absolute ether and reacted as in Example 1 65 with 32.5 g (O.l mol) of Ζ - β - [1 - phenyl 1 - hydroxypropyl - (2) - amino] - propio thienone-(3) hydrochloride (m.p. 195-196°C, prepared by reacting 3-acetyl-thiophene with paraformaldehyde and Z-norephedrin hydro- 70 chloride in isopropanol at boiling temperature) in 200 ml of absolute benzene). The reaction product is similarly worked up. The HQ salt is reciystallised from isopropanol, m.p, 220-221°C, yield 10 g. 75

Ζ - [1 - Thienyl - (3) - 1 - m,p - dimethyl -

phenyl - 1 - hydroxypropyl - (3)] - [1 phenyl-l-hydroxypropyl-(2)] -amine

OH ^^ch3

-c-ν \-ch₃

j ~ CHtOH) /3 80 CHg-CHg-Ν Η-CH

CH₃

A Grignard compound is prepared from 12.1 g (0.1 mol) of magnesium and 92.5 g (0.5 mol) of 4-bromoxylene in 150 ml of absolute ether, reacted as in Example 1, with 32.5 g (0.1' mol) of i - β - [1 - phenyl - 1 - 85 hydroxypropyl - (2) - amino] - propiothien οη℮-(3) hydrochloride in 200 ml of absolute benzene and the reaction product similarly worked up. The HCI salt is recrystallised from water. m.p. 185-188°C., yield 9 g. 90

A Grignard compound is prepared from 9.8 g (0.4 mol) of magnesium and' 62.8 g (0.4 mol) of bromobenzene in 120 ml of absolute ether, reacted as in Example 1 with 29.3 g (0.1 mol) of dj - β - [2 - (4 - fluoro phenyl) - 2 - hydroxyethylamino] - propio thienone-(3) hydrochloride (m.p. 152°C., prepared by reacting β - dimethylamino - pro piothienone - (3) hydrochloride with 2 - (4 fluorophenyl) - 2 - hydroxyethylamine in ethanol/water at room temperature) in 180 ml of benzene and the reaction product similarly worked up. The HQ salt is recrystallised from isopropanol, m.p. 180°C., yield 8 g.

2 - hydroxyethylamino] - propiothienone - (3) 50 hydrochloric (m.p. 160°C, prepared by reacting β - dimethylamino - propiothienone - (3) hydrochloride and 2 - (4 - chlorophenyl) - 2 hydroxyethylamine in ethanol/water at room temperature) in 150 ml of absolute benzene 55 and the reaction product similarly worked up.

The HQ salt is recrystallised from isopropanol/ether. m.p. 196°C, yield 4 g.

d,l - [1 - Thienyl - (3) - 1 - phenyl - 1 -

hydroxypropyl - (3)] - [2 - (4 - tert. butylphenyl)-2-hydroxyeihyl]-amine <7 .

<7

OH ,

S ^ I 'W f3 CH₂-CH₂-NH-CH₂-CH!OH)-f VC-CH₃^N~^V CH₃

A Grignard compound is prepared from 9.8 g (0.4 mol) of magnesium and 62.8 g (0.4 mol) of bromobenzene in 120 ml of absolute ether, reacted as in Example 1 with 26.5 g (0,08 mol) of d,l - β - [2 - (4 - tert.butyl phenyl) - 2 - hydroxyethylamino] - propio thienone-(3) (m.p. 133°C, prepared by reacting β - dimethylamino - propiothienone hydrochloride with 2 - (4 - tert.butylphenyl) - 2 hydroxyethylamine in ethanol/water at room temperature in 180 ml of absolute benzene and the reaction product similarly worked up. The HQ salt is recrystallised from isopro-. panol/ether m.p. 163°C. yield 3 g.

The β - dimethylamino - propiothienone hydrochloride used in Examples 8 and 9 is obtained from 3-acetyl-thiophene, paraformaldehyde and dimethylamine hydrochloride in the same way as the starting material for Example 1.

d,l - [1 - Thienyl - (3) - 1 - phenyl - 1 -

hydroxypropyl - (3)] - [4 - chloro phenyl)-2-hydroxyethyl]-amine

<7

OH

/Λ

ch₂-ch₂-nh-ch₂-ch(qhj-

4.1 g (0.01 mol) of I - [1 - thienyl - (3) 1 - phenyl - 1 - hydroxy - 2 - methylpropyl - 65 (3)] - [1 - phenyl - 1 - hydroxypropyl - (2)] amine hydrochloride are suspended in 30 ml of glacial acetic acid and the resulting suspension treated with HCI gas -until dissolution is complete. The solvent is distilled off, the 70 residue is alkalised with ammonia and the base dissolved in ether. The HC1 salt is prepared by neutralising the ethereal solution with isopropanolic HQ, and is recrystallised from isopropanol. m.p. 215-216°C, yield 3 g. 75

Example 11

1 - [1 - Thienyl - (3) - 1 - (4 - isopropyl -

phenyl) - propen - (1) - yl - (3)] - [1 phenyl-l-hydroxypropyl-(2)] -amine

<jH3

^s CH-CH₂-NH-CH ^-'

ch₃

80

4.4 g (0.01 mol) of 1 - [1 - thienyl - (3) 1 - ρ - isopropylphenyl - 1 - hydroxypropyl (3)] - [1 - phenyl - 1 - hydroxypropyl - (2)] amine hydrochloride are suspended in 30 ml of glacial acetic add and HCI gas introduced 85 to the resulting suspension for 30 minutes.

The.solvent is distilled off and the residue treated -with ammonia. The base is dissolved in ether and converted with isopropanolic HQ into the HQ salt which is recrystallised from 90 ethanol, m.p. 236-237°C, yield 2 g.

Example 12

I - [ 1 - Thienyl - (3) - 1 - phenyl - propen - I -

yl - (3)] - [h - phenyl - 1 - hydroxypro pyl-(2)] -methylamine 95

A Grignard compound is prepared from 7.3 g (0.3 mol) of magnesium and 47.1 g (0.3:

mol) of bromobenzene in 100 ml of absolute ether, reacted as in Example 1 with 20.8 g (0.06 mol) of ijt - β - [2 - (4 - chlorophenyl) <(V | Ο .CH₃ CH,OH)_0

⁵ CH-CH₂- CH

ch₃

5 A Grignard compound is prepared from 7.2 g (0.3 mol) of magnesium and 47.2 g (0.3 mol) of bromobenzene in 100 ml of absolute ether.

A suspension of 17 g (0.05 mol) of 1 - β - [1 phenyl - 1 - hydroxypropyl - (2) - methyl -

amino] - propiothienone - (3) hydrochloride (m.p. 145°C, prepared by reacting 3-acetyl-thiophene with paraformaldehyde and f-ephedrin hydrochloride in isopropanol at room temperature) in 100 ml of absolute benzene is added to the resulting solution which is then kept boiling for 3 hours. The product is' then decomposed with a solution of 25 g of ammonium chloride in 250 ml Of icewater, the organic phase is separated off, dried with potassium carbonate and the solvent distilled off. The base left behind is dissolved in ether, and converted with isopropanolic HC1 into the HQ salt, which is reciystallised from ethanol, m.p. 202-203 °C., yield 6 g.

Example 13

I - [1 - Thienyl - (3) - 1 - phenyl - 1 - (3,4 dimethylphenyl) - propen - (1) - yl (3)] - [1 - phenyl - 1 - hydroxypropyl (2)]-amine

<X1

,ch₃

-ch₃

CH(OH)-

CH-CH₂ ΝΗ CH

CH₃

-G

2 C(OH)-ΟΕ1)Η--

or the structure

2 C^QR¹)-;

R¹, R², R³ and R⁴, which may be the same or different, each represent a hydrogen atom or a lower molecular weight alkyl group, R⁵ represents a hydrogen atom or a hydroxyl group; R^c and R⁷, which may be die same or different, each represent a hydrogen or a halogen atom, a hydroxyl group, a lower molecular weight alkyl group, a lower molecular weight halogeno alkyl group or a lower molecular weight alkoxy group; and R⁵ and R⁹, which may be the same or different, each represent a hydrogen atom, a hydroxyl group, a lower molecular weight alkyl group or a lower molecular weight alkoxy group; their optically active and diastereomeric forms and their add addition salts.

2. The compounds corresponding to formula I as defined in Qaim 1 hereinbefore described in the Table and the Examples.

3. A process for the production of compounds as defined in Claim 1 in which > A-Β- has the structure

2 >C(OH)-QR^H-

which comprises reacting a compound of the general formula

21.6 g (0.05 mol) of 1 - [1 - thienyl - (3) 1 - ΐη,ρ - dimethylphenyl - 1 - hydroxypro pyl - (3)) - [1 - phenyl - 1 - hydroxypropyl (2)]-amine hydrochloride are suspended in 100 ml of glacial acetic acid and the resulting suspension treated with HQ gas until dissolution is complete. The solvent is distilled off, the residue treated with ammonia and the base dissolved in ether. It is converted with isopropanolic HQ into the HC1 salt which is recrystallised from 50% ethanol, m.p. 215-■ 217°C., yield 7 g.