The United States of America, As Represented by the Secretary, Department of Health and Human Services

Alchem Laboratories Corporation

Sergiy M Denysenko

Omar D Lopez

Paul S Liu

Lianhao Zhang

Joel Morris

Donn Gregory Wishka

Baburao Vishnuvajjala

Robert Bahde

Guangfei Huang

Methods for stereoselective synthesis and manufacturing of 2'-deoxynucleosides, such as 2&#x2032;-ribonucleosides, are disclosed. In some embodiments, the 2&#x2032;-deoxynucleoside is a &#x3b2;-anomer of a 2&#x2032;-deoxynucleoside having a 3&#x2032; &#x3b1; hydroxyl, 4&#x2032; &#x3b2; hydroxymethyl configuration. Nonlimiting examples of compounds prepared by the disclosed methods include 4&#x2032;-thio-2&#x2032;-deoxycytidine (T-dCyd) and 5-aza-4&#x2032;-thio-2&#x2032;-deoxycytidine (5-aza-T-dCyd; aza-T-dCyd; aza-T-dC).

Stereoselective synthesis and process for the manufacturing of 2'-deoxynucleosides

Disclosed is a process for preparing (Z)-endoxifen, comprising (i) recrystallizing an input crystalline solid comprising a mixture of (Z)-endoxifen (1) and (E)-endoxifen (2) from a first solvent to provide a first crystalline solid and a first mother liquor, wherein the first mother liquor has a ratio of (1) to (2) at least 1.3 times greater than the ratio in the input crystalline solid (1) and (2); (ii) recrystallizing a solid produced by concentrating the first mother liquor, or by removal of the first solvent from the first mother liquor, from a second solvent to give a second crystalline solid and a second mother liquor; (iii) optionally recrystallizing the second crystalline solid from the second solvent one to five additional times to give a third crystalline solid; wherein the third crystalline solid has a ratio of (Z)-endoxifen (1) to (E)-endoxifen (2) greater than 20:1. 

Process for preparing Z-endoxifen of high purity

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Alachua, FL, United States of America

Sergiy M Denysenko