Hanmi Pharm. Co., Ltd.

Hanmi Science Co., Ltd.

Moonsub Lee

Young-Kil Chang

Jaeheon Lee

Gwan Sun Lee

Gha-Seung Park

Han Kyong Kim

Hyo-Jeong Bang

Jae Chul Lee

Gwan-Sun Lee

Gha Seung Park

Hoe Chul Lee

Cheol Kyong Kim

Jae-Chul Lee

Cheol-Kyong Kim

Chang-Ju Choi

Cheol-Kyong Sinnamusil Sinmyeong Apt 634-1003 Kim

Gha-Seung Sinjeongmaeul 1-Danji 107-1003 Park

Jae-Chul Kyungwonyeonlip Ra-Dong 101 Lee

1-&#x3b1;-halo-2,2-difluoro-2-deoxy-D-ribofuranose derivative of formula (I) having the 3-hydroxy group protected with a biphenylcarbonyl group is a solid which can be easily purified by a simple procedure such as recrystallization, and therefore, it can be advantageously used as an intermediate in the preparation of gemcitabine in a large scale. Further, the 1-&#x3b1;-halo-2,2-difluoro-2-deoxy-D-ribofuranose derivative of formula (I) can be prepared with high stereoselectivity using the compound of formula (V) as an intermediate.

1-&#x3b1;-halo-2,2-difluoro-2-deoxy-D-ribofuranose derivatives and process for the preparation thereof

Provided is an improved method for stereoselectively preparing 2'-deoxy-2&#x2032;,2&#x2032;-difluorocytidine of formula (I), which includes reacting a 1-halo ribofuranose compound with a nucleobase of formula (IV) in a solvent to obtain a nucleo side of formula (II) with removal of a silyl halide ((alkyl)SiX (X=halide)); and deprotecting the nucleoside of formula (II) to obtain 2&#x2032;-deoxy-2&#x2032;,2&#x2032;-difluorocytidine of formula (I). 2&#x2032;-Deoxy-2&#x2032;,2&#x2032;-difluorocytidine of formula (I) is effective for treating various cancers such as non-small cell lung (NSCLC), pancreatic, bladder, breast or ovarian cancers. 

Method for the preparation of 2'-deoxy-2&#x2032;,2&#x2032;-difluorocytidine

3R-carboxylate enantiomer derivative of formula (III) can be prepared easily and selectively by the method of the present invention, and a highly pure D-erythro-2,2-difluoro-2-deoxy-1-oxoribose derivative can be prepared efficiently from the compound of formula (III) as an intermediate.

Method for the preparation of D-erythro-2,2-difluoro-2-deoxy-1-oxoribose derivative

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Daejeon, South Korea

Moonsub Lee