Method of preparing permissibly-substituted 1H(and 2H)pyrazolo[3,4-g]quinolines; pyrimido[4,5,g]quinolines; thiazolo[4,5,g]quinolines and intermediates therefore
AssigneeEli Lilly and Company
InventorJohn M. Schaus
Life of this patent
Estimating the term…
Abstract
Trans-(.+-.)-1-permissibly-substituted-2,6-dioxodecahydroquinoline or enantiomers thereof, intermediates for preparing tautomeric trans-(.+-.)-5-permissibly substituted octahydro-1H(and 2H)pyrazolo[3,4-g]quinolines, 4aR,8aR or 4aS,8aS enantiomers thereof, for preparing trans-(.+-.)-5-permissibly substituted-octahydropyrazolo (or oxazolo)[4,5-g]quinoline, 4aR,8aR or 4aS,8aS enantiomers thereof or for preparing trans-(.+-.)-6-permissibly-substituted octahydropyrimido[4,5-g]quinolines, a 5aR,9aR or 5aS,9aS enantiomer thereof said racemic intermediates being comprised of stereoisomers of the following formulas ##STR1## wherein R is H, alkyl or C.sub.1-3 straight-chain alkyl.
Claims29
The trans-(.+-.)-tautomers composed of the tautomeric enantiomers ##STR17## wherein R is H, allyl or C.sub.1-3 straight-chain alkyl.
The trans-(.+-.)racemate composed of trans-(-) and trans-(+)enantiomers of the formula ##STR18## wherein R is H, allyl or C.sub.1-3 straight-chain alkyl, R.sup.1 and R.sup.2 are individually H, methyl, ethyl or n-propyl, and Y is S or O.
A trans-(.+-.)racemate composed of enantiomers of the formulas ##STR19## wherein R is H, allyl or C.sub.1-3 straight-chain alkyl, and R.sup.1 and R.sup.2 are individually H or C.sub.1-3 straight chain alkyl.
A trans-(.+-.)racemate composed of enantiomers of the formula ##STR20## wherein R is H, allyl or C.sub.1-3 straight-chain alkyl.
A trans-(.+-.)racemate composed of enantiomers of the formula ##STR21## wherein R is H, allyl or C.sub.1-3 straight-chain alkyl, and, when taken singly, one of R.sup.4 and R.sup.5 is H and the other Br or formyl and when taken together, R.sup.4 and R.sup.5 represent dimethylaminomethylene.
Compounds of the formulas ##STR22## wherein R is C.sub.1-3 alkyl or H, Z and Z.sup.1 with the carbon to which they are attached represent a carbonyl or an ethylene ketal, P is H, C.sub.1-3 alkyl or a protecting group, CO--W, wherein W is phenyl C.sub.1-2 alkyloxy, C.sub.1-3 alkyloxy, H or C.sub.1-3 alkyl.
The process which comprises hydrogenating over a nobel metal catalyst a trans racemate of the formula ##STR23## wherein W is O--C.sub.1-3 alkyl or --O--C.sub.1-2 alkylphenyl, Z.sup.2 and Z.sup.3 are, individually, C.sub.1-2 alkyloxy and, taken together, O--(CH.sub.2).sub.2 --O to yield a trans racemate of the formula ##STR24## alkylating or allylating said cyclic lactam with a straight chain C.sub.1-3 alkyl halide or allyl halide in the presence of a base to yield a trans racemate of the formula ##STR25## wherein R is C.sub.1-3 straight chain alkyl or allyl and Z.sup.2 and Z.sup.3 have their previous meaning, treatment of which with acid in a mutual solvent, yields a trans racemate of the formula ##STR26## wherein R has its previous meaning and then, optionally, reacting said compound with tridimethylaminomethane to yield a trans racemate of the formula ##STR27## wherein R has its previous meaning.
The process which comprises hydrogenating over a noble metal catalyst a trans racemate of the formula ##STR28## wherein W is O--C.sub.1-3 alkyl or --O--C.sub.1-2 alkylphenyl, Z.sup.2 and Z.sup.3 are, individually, C.sub.1-2 alkyloxy and, taken together, O--(CH.sub.2).sub.2 --O to yield a trans racemate of the formula ##STR29## treatment of which with acid in a mutual solvent yields a trans racemate of the formula ##STR30## and then, optionally, reacting said compound with tridimethylaminomethane to yield a trans racemate of the formula ##STR31##
The process step which comprises simultaneously hydrogenating, deprotecting and cyclizing a trans racemate of the formula ##STR32## wherein W is O--C.sub.1-3 alkyl or O--C.sub.1-2 alkylphenyl and Z.sup.2 and Z.sup.3, taken individually are C.sub.1-2 alkyl and taken together O--(CH.sub.2).sub.2 --O, to yield a trans racemate of the formula ##STR33## wherein Z.sup.2 and Z.sup.3 have their previous meaning.
Dependencies are inferred from the claim text.