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