Processes and intermediates for the preparation of 1′-substituted carba-nucleoside analogs

Patent metadata

Field	Value
Publication number	US-10023600-B2
Application number	US-88624810-A
Country	US
Kind code	B2
Filing date	Sep 20, 2010
Priority date	Sep 21, 2009
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

Provided are processes and intermediates for the syntheses of nucleosides of pyrrolo[1,2-f][1,2,4]triazinyl and imidazo[1,2-f][1,2,4]triazinyl heterocycles of Formula I.

First claim

What is claimed is:

1. A compound of Formula VId:

or an acceptable salt, thereof;
wherein:
R 1 is H, or (C 1 -C 8 )alkyl;
R 7 is —C(R 5 ) 2 R 6 , Si(R 3 ) 3 , or

each R 3 is independently (C 1 -C 8 )alkyl, (C 1 -C 8 ) substituted alkyl, C 6 -C 20 aryl, C 6 -C 20 substituted aryl, C 2 -C 20 heterocyclyl, C 2 -C 20 substituted heterocyclyl, C 7 -C 20 arylalkyl, C 7 -C 20 substituted arylalkyl, (C 1 -C 8 )alkoxy, or (C 1 -C 8 ) substituted alkoxy;
each R 5 is independently H, (C 1 -C 8 )alkyl, (C 1 -C 5 ) substituted alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 ) substituted alkenyl, (C 2 -C 8 )alkynyl, (C 2 -C 8 ) substituted alkynyl, C 6 -C 20 aryl, C 6 -C 20 substituted aryl, C 2 -C 20 heterocyclyl, substituted heterocyclyl, C 7 -C 20 arylalkyl, or C 7 -C 20 , substituted arylalkyl;
each R 6 is independently C 6 -C 10 aryl, C 2 -C 20 substituted aryl, or optionally substituted heteroaryl;
each R a is independently H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, aryl(C 1 -C 8 )alkyl, (C 4 -C 8 )carbocyclylalkyl, —C(═O)R 11 , —C(═O)OR 11 , —C(═O)NR 11 R 12 ; —C(═O)SR 11 , —S(O)R 11 , —S(O) 2 R 11 , —S(O)(OR 11 ), —S(O) 2 (OR 11 ), or —SO 2 NR 11 R 12 ;
X 1 is CH;
each X 2 is O or CH 2 ;
each m is 1 or 2;
each n is independently 0, 1 or 2;
each R 8 is NH 2 ;
R 9 is H;
each R 11 or R 12 is independently H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 8 )carbocyclyl, (C 4 -C 8 )carbocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)(C 1 -C 8 )alkyl, —S(O) n (C 1 -C 8 )alkyl, aryl(C 1 -C 8 )alkyl or Si(R 3 ) 3 ; or R 11 and R 12 taken together are —Si(R 3 ) 2 (X 2 ) m Si(R 3 ) 2 —;
R 17 is OH;
each R 19 is methyl;
wherein each (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl or (C 2 -C 8 )alkynyl of each R 1 , R 3 , R 5 or R 6 is independently, optionally substituted with one or more halo, hydroxy, CN, N 3 , N(R a ) 2 or OR a , and wherein one or more of the non-terminal carbon atoms of each said (C 1 -C 8 )alkyl is optionally replaced with —O—, —S(O) n — or —NR a —.

2. The compound of claim 1 that is

or an acceptable salt thereof.

Assignees

• Butler Thomas
• Cho Aesop
• Graetz Benjamin R
• Kim Choung U
• Metobo Samuel E
• Saunders Oliver L
• Waltman Andrew W
• Xu Jie
• Zhang Lijun
• Gilead Sciences Inc

Inventors

• Butler Thomas
• Cho Aesop
• Graetz Benjamin R
• Kim Choung U
• Metobo Samuel E
• Saunders Oliver L
• Waltman Andrew W
• Xu Jie
• Zhang Lijun

Classifications

• A61P31/12

  Antivirals · CPC title

• C07H19/23 Primary

  Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22 · CPC title

• C07H19/00

  Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides ; Anhydro-derivatives thereof · CPC title

• A61K31/7056

  containing five-membered rings with nitrogen as a ring hetero atom · CPC title

• A61K31/706

  containing six-membered rings with nitrogen as a ring hetero atom · CPC title