Patent ID: 6355807
Filing Date: 2002-03-12
Classification: B01J,C07B,C07C,C07D

Abstract:
A process useful in synthesizing antipicornaviral compounds, comprising:(a) performing cyanomethylation of a compound of formula V using bis(trimethysily)amide and bromoacetonitrile to yield a compound of formula VI; (b) performing reduction, then cyclization, and then deprotection of the compound of formula VI to yield a compound of formula VII; and (c) performing oxidation and olefination of the compound of formula VIl by reacting the compound of formula VII with a SO3-pyridine complex to yield a â€ƒreaction mixture and reacting the reaction mixture with a compound for formula VIII to form a compound of formula IV: (d) deprotecting the compound of formula IV to yield a compound of formula IVA: (e) subjecting a compound of formula II and the compound of formula IVA to an amide-forming reaction to yield a compound of formula IA: wherein each R41 is independently H or lower alkyl, R4 is R5 and R6 are each independently H, F, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group; and Z and Z1 are each independently H, F, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, â€”C(O)R21, â€”CO2R21, CN, â€”C(O)NR21R22, â€”C(O)NR21OR22, â€”C(S)R21, â€”C(S)NR21R22, â€”NO2, â€”SOR21, â€”SO2R21, wherein R1 is H, F, an alkyl group, OH, SH, or an O-alkyl group; wherein each R41 is independently H or lower alkyl; wherein X is any suitable protecting group for nitrogen and wherein Z and Z1 are each independently H, F, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, â€”C(O)R21, â€”CO2R21, CN, â€”C(O)NR21R22, â€”C(O)NR21OR22, â€”C(S)R21, â€”C(S)NR21R22, â€”NO2, â€”SOR21, â€”SO2R21, â€”SO2NR21R22, â€”SO(NR21)(OR22), â€”SONR21, â€”SO3R21, â€”PO(OR21)2, â€”PO(R21)(R22), â€”PO(NR21R22)(OR23), â€”PO(NR21R22)(NR23R24), â€”C(O)NR21NR22R23, or â€”C(S)NR21NR22R23, where R21, R22, R23, and R24 are each independently H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, an acyl group, or a thioacyl group, or where any of two of R21, R22, R23, and R24, together with the atom(s) to which they are bonded, form a heterocycloalkyl group, provided that Z and Z1 are not both H; or Z1 and R1, together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z1 and R1 are as defined above except for moieties that cannot form the cycloalkyl or heterocycloalkyl group; or Z and Z1, together with the atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, where Z and Z1 are as defined above except for moieties that cannot form the cycloalkyl or heterocycloalkyl group.