Process for making chloro-substituted nucleoside phosphoramidate compounds

Patent metadata

Field	Value
Publication number	US-10597422-B2
Application number	US-201916248273-A
Country	US
Kind code	B2
Filing date	Jan 15, 2019
Priority date	Feb 8, 2016
Publication date	Mar 24, 2020
Grant date	Mar 24, 2020

Abstract

The present invention is directed to a process for making Chloro-Substituted Nucleoside Phosphoramidate Compounds of formula (I):

which are useful for the treatment and prophylaxis of HCV infection. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

First claim

What is claimed is:

1. A compound having the formula:

X is selected from C 1 -C 6 alkylene, C 6 -C 10 arylene, C 4 -C 10 cycloalkylene, 5 or 6-membered monocyclic heteroarylene and 9 or 10-membered bicyclic heteroarylene, wherein said C 6 -C 10 arylene group, said C 4 -C 10 cycloalkylene group, said 5 or 6-membered monocyclic heteroarylene group and said 9 or 10-membered bicyclic heteroarylene group can be optionally substituted with one or more R 5 groups;
each occurrence of R 5 is independently selected from —C 1 -C 6 alkyl, halo, —OR 6 , —C(O)R 6 , —CO 2 R 6 , —SR 6 , —C 1 -C 6 hydroxyalkyl, —C 1 -C 6 haloalkyl, —N(R 6 ) 2 , —S(O)R 6 , —S(O) 2 R 6 , —CN and —NO 2 ;
each occurrence of R 6 is independently selected from H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, —(C 1 -C 3 alkylene) m -(C 3 -C 7 cycloalkyl), —(C 1 -C 3 alkylene) m -(C 6 -C 10 aryl), —(C 1 -C 3 alkylene) m -(4 to 7-membered heterocycloalkyl), —(C 1 -C 3 alkylene) m -(5- or 6-membered monocyclic heteroaryl) and —(C 1 -C 3 alkylene) m -(9- or 10-membered bicyclic heteroaryl);
each occurrence of R 7 is independently selected from H, C 1 -C 6 alkyl, phenyl, C 3 -C 7 cycloalkyl, 4 to 7-membered monocyclic heterocycloalkyl and 5- or 6-membered monocyclic heteroaryl;
each occurrence of R 8 is independently selected from H, C 1 -C 6 alkyl, phenyl, C 3 -C 7 cycloalkyl, 4 to 7-membered monocyclic heterocycloalkyl and 5- or 6-membered monocyclic heteroaryl;
each occurrence of m is independently 0 or 1;
p is 2, 3, 4 or 5; and
q is 2, 3, 4 or 5.

2. The compound of claim 1 , having the structure:

Assignees

• Merck Sharp & Dohme

Inventors

• Dirocco Daniel
• Klapars Artis
• Sherer Edward C

Classifications

• C07H19/10 Primary

  with the saccharide radical esterified by phosphoric or polyphosphoric acids · CPC title

• C07H1/02

  Phosphorylation · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07H9/06

  the hetero ring containing nitrogen as ring hetero atoms · CPC title