Taro Pharmaceuticals U.s.a., Inc.

Taro Pharmaceutical Industries Limited

Taro Pharmaceuticals North America, Inc.

Taro Pharmaceutical North America, Inc.

Shimon Chernyak

Daniella Gutman

Wael Baidossi

Martin Zarbov

Sorin Bercovici

Konstantin Ulanenko

The present invention provides a process for preparing a crystalline form of halobetasol propionate, comprising the step of crystallizing halobetasol propionate from absolute ethanol or a mixture of ethanol and water, wherein the crystalline form of halobetasol propionate is characterized by an x-ray powder diffraction pattern having peaks at 10.0, 11.6, 12.9, 13.4, 14.5, 16.4, 17.6, and 23.5&#xb1;0.2 degrees 2&#x3b8;.

Process for preparing a crystalline form of halobetasol propionate

The present invention provides a method of preparing a 4-(arylmethyl)amino-1H-imidazo(4,5-c)quinoline of formula (4) by reacting an arylmethylamine of formula (3) with a 4-chloro-1H-imidazo(4,5-c)quinoline of formula (2). The present invention further provides a method of preparing an acid addition salt of formula (5) comprising the step of hydrolyzing a 4-(arylmethyl)amino-1H-imidazo(4,5-c)quinoline of formula (4) with a strong acid, HX. The present invention further provides a method of preparing a 4-amino-1H-imidazo(4,5-c)quinoline of formula (1) comprising the step of treating an acid addition salt of formula (5) with a base.

[object Object]

A method for producing a 6&#x3b1;-fluorinated corticosteroid or derivative thereof by reacting a 17-hydroxy-21-ester epoxide of Formula II with a stereoselective fluorinating agent to stereoselectively form a 21-ester-17-hydroxy 6&#x3b1;-fluorinated compound of Formula VII Rcan be OC(O)&#x2014;R; Rcan be C(O)&#x2014;R; Rcan be H or R. Each Rmay be the same or different and is independently selected from (C)alkyl, aryl and heteroaryl. The dashed line can be a single or a double bond. Rmay be, for example, acetyl; Rmay be, for example, alpha or beta methyl; Rmay be, for example, acetate or propionate, The stereoselective fluorinating agent used in the reaction may be, for example, a fluoropyridinium or fluoroquinuclidium compound, for example, Selectfluor&#xae;.

Method for the preparation of 6-&#x3b1; fluoro corticosteroids

A method for producing a 6&#x3b1;-fluorinated corticosteroid or derivative thereof by reacting a 17-hydroxy-21-ester epoxide of Formula II with a stereoselective fluorinating agent to stereoselectively form a 21-ester-17-hydroxy 6&#x3b1;-fluorinated compound of Formula VII Rcan be OC(O)&#x2014;R; Rcan be C(O)&#x2014;R; Rcan be H or R. Each Rmay be the same or different and is independently selected from (C)alkyl, aryl and heteroaryl. The dashed line can be a single or a double bond. Rmay be, for example, acetyl; Rmay be, for example, alpha or beta methyl; Rmay be, for example, acetate or propionate. The stereoselective fluorinating agent used in the reaction may be, for example, a fluoropyridinium or fluoroquinuclidium compound, for example, Selectfluor&#xae;.

Method for the preparation of 6&#x3b1;-fluoro corticosteroids

The present invention is a method for producing warfarin sodium from warfarin sodium 2-propanol clathrate by thermal, nondestructive solvent expulsion. The solvent expulsion is conducted under conditions of controlled heat transfer whereby the 2-propanol is expelled from the warfarin sodium 2-propanol clathrate without decomposition of warfarin sodium or the clathrate. Heating is conducted the clathrate at a temperature from about 100&deg; C. to about 170&deg; C. in an active oven under air or in an inert atmosphere and at partial pressures ranging from that of a relative vacuum to atmospheric pressure. The invention also relates to pure warfarin sodium prepared according to the method of the invention and pharmaceutical compositions containing warfarin sodium.

Growing community of inventors

Yokneam Llit, Israel

Shimon Chernyak