Cyanocarboxamidines and quinazoline process
AssigneeBristol-Myers Company
InventorsRonnie R. Crenshaw, George M. Luke, Richard A. Partyka
Life of this patent
Estimating the term…
Abstract
Novel cyanocarboxamidines are disclosed. The new cyanocarboxamidines are particularly valuable as intermediates in the preparation of antihypertensive 4-amino-2-(4-substituted-piperazin-1-yl)-quinazolines.
Claims20
A compound selected from the group consisting of cyanocarboxamidines having formula II ##STR28## wherein n is equal to 2 to 3,
- A is hydrogen or lower alkyl of 1 to 4 carbon atoms inclusive;
- B and C are independently selected from the group consisting of lower alkoxy of 1 to 4 carbon atoms inclusive,
- R.sub.1 is selected from the group consisting of lower alkyl of from 1 to 6 carbon atoms inclusive, R.sub.2 C.dbd.O in which R.sub.2 is cycloalkenyl, cycloalkyl, methylcycloalkyl in which cycloalkyl and cycloalkenyl are from 3 to 8 carbon atoms inclusive, hydroxyalkoxy of from 2 to 6 carbon atoms inclusive or phenyl, and ZC.dbd.O in which Z is a heterocyclic radical selected from the group consisting of ##STR29## in which X is either oxygen or sulfur, R.sub.a is lower alkyl of 1 to 6 carbon atoms inclusive, R.sub.b is selected from the group consisting of hydrogen, amino, lower alkyl of 1 to 4 carbon atoms inclusive and NHCO.sub.2 R.sub.c in which R.sub.c is lower alkyl of 1 to 4 carbon atoms inclusive, R.sub.d and R.sub.e are independently selected from the group consisting of hydrogen, lower alkyl of 1 to 6 carbon atoms inclusive, lower alkoxy of 1 to 6 carbon atoms inclusive, and lower alkylthio of 1 to 6 carbon atoms inclusive.
The compound of formula II which is 4-methyl-piperazine-1-[N-cyano-N'-(3,4-dimethoxyphenyl)]carboxamidine.
The compound of formula II which is 4-(2-furoyl)piperazine-1-[N-cyano-N'-(3,4-dimethoxyphenyl)]carboxamidine.
The compound of formula II which is 4-(5-methylthio-1,3,4-oxadiazole-2-carbonyl)piperazine-1-[N-cyano-N'-(3,4- dimethoxyphenyl)]carboxamidine.
A process for preparing a quinazoline compound of formula I ##STR30## wherein n is equal to 2 or 3;
- A is hydrogen or lower alkoxy of 1 to 4 carbon atoms inclusive;
- B and C are independently selected from the group consisting of lower alkoxy of 1 to 4 carbon atoms inclusive;
- R.sub.1 is selected from the group consisting of lower alkyl of from 1 to 6 carbon atoms inclusive;
- R.sub.2 CO in which R.sub.2 is cycloalkenyl, cycloalkyl, methylcycloalkyl in which cycloalkyl and cycloalkenyl are from 3 to 8 carbon atoms inclusive;
- hydroxyalkoxy from 2 to 6 carbon atoms inclusive or phenyl;
- and ZC.dbd.O in which Z is a heterocyclic radical selected from the group consisting of ##STR31## in which X is either oxygen or sulfur, R.sub.a is lower alkyl of 1 to 6 carbon atoms inclusive, R.sub.b is selected from the group consisting of hydrogen, amino, lower alkyl of 1 to 4 carbon atoms inclusive and NHCO.sub.2 R.sub.c in which R.sub.c is lower alkyl of 1 to 4 carbon atoms inclusive, R.sub.d and R.sub.e are independently selected from the group consisting of hydrogen, lower alkyl of 1 to 6 carbon atoms inclusive, lower alkoxy of 1 to 6 carbon atoms inclusive, and lower alkylthio of 1 to 6 carbon atoms inclusive
- which comprises cyclizing a cyanocarboxamidine of formula II ##STR32## wherein the symbols "A, B, C, n and R.sub.1 " are as recited above.
A process for the preparation of a quinazoline of formula Ia ##STR33## which comprises cyclizing a cyanocarboxamidine having formula IIa ##STR34##
A process for the preparation of a quinazoline of formula Ib ##STR35## which comprises cyclizing a cyanocarboxamidine having formula IIb ##STR36##
A process for the preparation of a quinazoline of formula Ic ##STR37## which comprises cyclizing a cyanocarboxamidine having formula IIc ##STR38##
A process for the preparation of a quinazoline of formula Id ##STR39## which comprises cyclizing a cyanocarboxamidine having formula IId ##STR40##
Dependencies are inferred from the claim text.