Teva Pharmaceutical Industries Limited

Bk Giulini Gmbh

Evgeny Shapiro

Ben-Zion Dolitzky

Ronit Yahalomi

Boaz Gome

Yigael Gozlan

Shlomit Wizel

Kobi Chen

Reinhard Effenberger

Asher Maymon

Valerie Niddam-Hildesheim

Thomas Staffel

Greta Sterimbaum

Anchel Schwartz

Santiago Ini

Eli Lancry

Ayelet Fishman

Yaron Shmuely

Igal Gozlan

Konstantin Panagiotidis

Provided is a method of selectively enzymatically esterifying or selectively enzymatically solvolyzing epimers of analogs of vitamin D having a stereogenic center at C-24 that has a free or esterified OH group. The metod can be used, for example, for separating mixed epimers of the vitamin D analog.

Selective enzymatic esterification and solvolysis of epimeric vitamin D analog and separation of the epimers

The present invention provides 3-benzyloxy-2-aminopyridine (BOPA), 3-(2-Hydroxyethyl)-2-methyl-9-hydoxy-4H-pyrido[1,2-a]pyrimidine-4-one (HMBP), 3-(2-Chloroethyl)-2-methyl-9-hydoxy-4H-pyrido[1,2-a]pyrimidine-4-one (CMHP) and 3-(2-chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrrido[1,2-a]-pyrimidin-4-one (CMHTP) useful as intermediates for the preparation of paliperidone. The present invention also provides processes for preparing these intermediates and for preparing paliperidone.

Process for the synthesis of CMHTP and intermediates thereof

The present invention provides methods of purifying montelukast, a new isolated impurity of montelukast, method for its isolation, and method of using montelukast impurity as a reference marker and a reference standard.

Purification of montelukast

The present invention provides processes for preparing montelukast.

Processes for preparing montelukast sodium

Provides are crystalline forms of nateglinide, labeled Forms A, C, D, F, G, I, J, K, L, M, N, 0, P, Q, T, U, V, Y, &#x3b1;, &#x3b2;, &#x3b3;, &#x3b4;, &#x3b5;, &#x3c3;, &#x3b8; and &#x3a9;, processes for their preparation and processes for preparation of other crystalline forms of nateglinide. Also provided are their pharmaceutical formulations and methods of administration.

Polymorphic forms of nateglinide

Provides are crystalline forms of nateglinide, labeled Forms A, C, D, F, G, I, J, K, L, M, N, O, P, Q, T, U, V, Y, &#x3b1;, &#x3b2;, &#x3b3;, &#x3b4;, &#x3b5;, &#x3c3;, &#x3b8; and &#x3a9;, processes for their preparation and processes for preparation of other crystalline forms of nateglinide. Also provided are their pharmaceutical formulations and methods of administration.

Provided is a method of general applicability of epimerizing a vitamin-D analog having an asymmetric allylic carbon atom at the C-24 position. The method is of particular utility in making calcipotriene.

Epimerization of analogs of vitamin D

Provided is a process for preparation of an intermediate in the synthesis of nateglinide. Trans-4-isopropylcyclohexane acid chloride is formed by reacting 4-isopropylcyclohexanecarboxyl acid with thionyl chloride in the presence of an effective amount of an organic amide. Also provided are processes for preparation of nateglinide by acylation of a suitable salt of D-phenylalanine with trans-4-isopropylcyclohexane acid chloride in both a single and a two phase system, and in water free of a co-solvent.

Growing community of inventors

Haifa, Israel

Evgeny Shapiro