11-01-2018 дата публикации
Номер: US20180010158A1
Принадлежит:
The present invention provides a process for the preparation of tofacitinib citrate of Formula I. Specifically, the present invention provides an enzymatic route for the preparation of tofacitinib of Formula II, which is converted to tofacitinib citrate of Formula I. 3. The process according to claim 1 , wherein the enzyme is selected from the group consisting of lipases and proteases.4Candida antarcticaRhizopus arrhizusCandida cylindraceaCandida antarctica. The process according to claim 3 , wherein the lipases are selected from the group consisting of Lipozyme® RM IM claim 3 , Novozym® 435 claim 3 , Savinase® 12T claim 3 , Lipozyme® TL IM claim 3 , Lipase PS “Amano®” SD claim 3 , Lipase AS “Amano® claim 3 ,” Acylase “Amano® claim 3 ,” SPRIN Anti CAL claim 3 , immobilized lipase B adsorbed on a highly hydrophobic polymer claim 3 , lipase from claim 3 , lipase from claim 3 , lipase from claim 3 , Addzyme TL 165G claim 3 , Addzyme RD 165G claim 3 , Addzyme CALB 165G claim 3 , FermaseCALB™ 10000 claim 3 , and adsorbed CALB.5. The process according to claim 3 , wherein the proteases are selected from the group consisting of Protease S “Amano® claim 3 ,” Protease N “Amano® claim 3 ,” and Subtilisin A.6. The process according to claim 1 , wherein the reaction of the compound of Formula III with the compound of Formula IV is carried out in a solvent.7. The process according to claim 6 , wherein the solvent is selected from the group comprising of hydrocarbons claim 6 , halogenated hydrocarbons claim 6 , ethers claim 6 , ketones claim 6 , esters claim 6 , alcohols claim 6 , amides claim 6 , dimethyl sulfoxide claim 6 , and mixtures thereof.8. The process according to claim 7 , wherein the hydrocarbons are selected from the group consisting of toluene claim 7 , hexane claim 7 , heptane claim 7 , cyclohexane claim 7 , cyclopentane claim 7 , cycoheptane claim 7 , benzene claim 7 , xylene claim 7 , and mixtures thereof.9. The process according to claim 7 , wherein the ...
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