Patent ID: 7169918
Filing Date: 2007-01-30
Classification: A61P,C07H

Abstract:
1. A method for preparing 7-(2′-R 1 -substituted-β-D-ribofuranosyl)-4-(NR 2 R 3 )-5-(ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine of formula I: wherein: R R which method comprises: (a) contacting at least a stoichiometric equivalent of 4,5-dihalo-7H-pyrrolo[2,3-d]pyrimidine with 1-bromo-3,5-di-O-protected 2-R (b) removing the protecting groups on the compound prepared in (a) above to provide for 7-(2′-R (c) selectively aminating the 4-halo group on said 7-(2′-R (d) contacting the 7-(2′-R (e) removing said protecting group on said 5-(protected ethyn-1-yl) to provide for 7-(2′-R substituted alkyl refers to an alkyl group having from 1 to 3 substituents selected from the group consisting of alkoxy, substituted alkoxy, aryl, substituted aryl, halogen, hydroxy, nitro, carboxyl, carboxyl ester, heteroaryl, substituted heteroaryl, heterocyclyl, and substituted heterocyclyl; alkoxy refers to alkyl-O—; alkoxyalkyl refers to -alkylene(alkoxy) substituted alkoxy refers to (substituted alkyl)-O—; substituted alkenyl refers to an alkenyl group having from 1 to 3 substituents selected from the group consisting of alkoxy, substituted alkoxy, aryl, substituted aryl, halogen, hydroxy, nitro, carboxyl, carboxyl ester, heteroaryl, substituted heteroaryl, heterocyclyl, and substituted heterocyclyl, provided that any hydroxy substitution is not on a vinyl carbon atom; substituted alkynyl refers to an alkynyl group having from 1 to 3 substituents selected from the group consisting of alkoxy, substituted alkoxy, aryl, substituted aryl, halogen, hydroxy, nitro, carboxyl, carboxyl ester, heteroaryl, substituted heteroaryl, heterocyclyl, and substituted heterocyclyl; acyl refers to a moiety selected from the group consisting of alkyl-C(O)—, substituted alkyl-C(O)—, alkenyl-C(O)—, substituted alkenyl-C(O)—, alkynyl-C(O)—, substituted alkynyl-C(O)—, cycloalkyl-C(O)—, substituted cycloalkyl-C(O)—, aryl-C(O)—, substituted aryl-C(O)—, heteroaryl-C(O)—, substituted heteroaryl-C(O), heterocyclyl-C(O)—, and substituted heterocyclyl-C(O)—; amino refers to —NH substituted amino refers to NR′R″ where R′ and R″ are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl and where R′ and R″ are joined, together with the nitrogen bound thereto to form a heterocyclyl or substituted heterocyclyl group provided that R′ and R″ are both not hydrogen; aryl refers to a monovalent aromatic carbocyclic group of from 6 to 14 carbon atoms having a single ring or multiple condensed rings, which condensed rings may or may not be aromatic provided that the point of attachment is at an aromatic carbon atom; substituted aryl refers to an aryl group substituted with from 1 to 3 substituents selected from the group consisting of hydroxy, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amino, substituted amino, aryl, substituted aryl, carboxyl, carboxyl ester, cyano, cycloalkyl, substituted cycloalkyl, halo, nitro, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl; carboxyl refers to —COOH or salts thereof; carboxyl ester refers to a moiety selected from the group consisting of —C(O)O-alkyl, —C(O)O-substituted alkyl, —C(O)Oaryl, and —C(O)O-substituted aryl; cycloalkyl refers to cyclic alkyl groups of from 3 to 10 carbon atoms having single or multiple cyclic rings one or more of which may be aromatic or heteroaromatic provided that the point of attachment is through a cycloalkyl ring atom; substituted cycloalkyl refers to a saturated or unsaturated, but not aromatic, cycloalkyl having from 1 to 5 substituents selected from the group consisting of oxo (═O), thioxo (═S), alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aryl, substituted aryl, aryloxy, substituted aryloxy, cyano, halogen, hydroxyl, nitro, carboxyl, carboxyl ester, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclyl, and substituted heterocyclyl; formyl refers to HC(O)—; halogen refers to fluoro, chloro, bromo or iodo; heteroaryl refers to an aromatic group of from 1 to 10 carbon atoms and 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen, sulfur in the ring, where the sulfur and nitrogen heteroatoms atoms can be present in their oxidized forms, such as >N(O), >S(O) and >S(O) substituted heteroaryl refers to a heteroaryl group substituted with from 1 to 3 substituents selected from the group consisting of hydroxy, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amino, substituted amino, aryl, substituted aryl, carboxyl, carboxyl ester, cyano, cycloalkyl, substituted cycloalkyl, halo, nitro, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl; heterocyclyl refers to a saturated or unsaturated group having a single ring or multiple condensed rings, from 1 to 10 carbon atoms and from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur or oxygen within the ring wherein, in fused ring systems, one or more the rings can be cycloalkyl, aryl or heteroaryl provided that the point of attachment is through the heterocyclyl ring; and substituted heterocyclyl refers to a heterocyclyl groups substituted with from 1 to 3 substituents selected from the group consisting of oxo (═O), thioxo (═S), alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aryl, substituted aryl, aryloxy, substituted aryloxy, cyano, halogen, hydroxyl, nitro, carboxyl, carboxyl ester, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclyl, and substituted heterocyclyl.