Heterocyclopyrimidines, compositions and therapeutic process

Claim 1

The process for preparing a compound selected from the group consisting of I II wherein R1 is hydrogen or the group A wherein A is lower alkyl, or lower alkenyl each having up to 8 carbon atoms, pyridylmethyl, aralkyl having 7 to 12 carbon atoms, substituted aralkyl having 7 to 12 carbon atoms, aryloxyalkyl having 8 to 12 carbon atoms, or substi-tuted aryloxyalkyl having 8 to 12 carbon atoms wherein each of said substituted aralkyl, and substituted aryloxyalkyl groups contains 1 or 2 substituents selected from halogen, alkoxy, and alkyl, and each of said alkoxy and alkyl groups contains up to 6 carbon atoms, R2 is hydrogen, trifluoromethyl, halogen, azido, cyano, amino, lower alkylamino, diloweralkylamino, or lower alkyl wherein said lower alkyl groups have up to 8 carbon atoms, R4 is hydrogen, lower alkyl or lower alkenyl each having up to 8 carbon atoms, pyridylmethyl, lower alkanoyl or lower alkenoyl each having up to 8 carbon atoms, aroyl having 7 to 10 carbon atoms, substituted aroyl having 7 to 12 carbon atoms,, aralkyl having 7 to 12 carbon atoms, substituted aralkyl having 7 to 12 carbon atoms, aryloxyalkyl having 8 to 12 carbon atoms, or substituted aryloxyalkyl having 8 to 12 carbon atoms wherein each of said substituted aroyl, substituted aralkyl, and substituted aryloxyalkyl groups contains 1 or 2 ring substituents selected from halogen, alkoxy, and alkyl, and each of said alkoxy and alkyl groups contains up to 6 carbon atoms, R6 and R7 represent carbon attached ring substituents and are selected from hydrogen, methyl, and ethyl, n is the integer 1, 2, or 3, and Z is oxo or imino, and the pharmaceutically acceptable acid addition salts of the fore-going compounds, and the pharmaceutically acceptable metal, ammonium and amine salts of the foregoing compounds wherein R1 is hydrogen, characterized by reducing a compound having the Formula III III wherein Z, R1, R6, R7 and n are as previously defined, and B is nitroso, under formylating conditions when a compound of Formula I is desired and under non-formylating conditions when a compound of Formula II is desired, respectively yielding the mono-formyldiaminopyrimidine of Formula III wherein B is the HCONH group or the diaminopyrimidine of Formula III wherein B is the H2N group and thereafter cyclizing said compound of Formula III (B is H2N- or HCONH-) to yield a compound of Formula I or Formula II and, when a compound of Formula I or Formula II is desired having R4 = alkanoyl, aroyl or substituted aroyl, reacting a substance of Formula I or Formula II wherein R4 is hydrogen with an acylating agent capable of introducing said alkanoyl, aroyl or substituted aroyl group under conditions known for the production of amides from aromatic amines and, when a compound of Formula I is desired having R2 = halogen, treating a compound of Formula I wherein R2 = hydrogen with a halogenating agent known to be suitable for introducing a halogen atom into an aromatic compound and, when a compound of Formula I or Formula II wherein R1 is the group A, as previously defined, converting a compound of Formula I or Formula II wherein R1 is hydrogen to an alkali metal salt by treatment thereof with a strong alkali metal base and reacting the resulting alkali metal salt with a halide, phosphate or sulfate reactant of Formula AX wherein X is the halide, phosphate, or sulfate group and A is as previously defined and, when a pharmaceutically acceptable acid addition salt of a compound having Formula I or Formula II is desired. reacting a compound of Formula I or Formula II with a pharmaceutically acceptable acid and, when a pharmaceutically acceptable metal, ammonium or amine salt of a compound having Formula I or Formula II is desired, reacting a compound of Formula I or Formula II wherein R1 = hydrogen with a pharmaceutically acceptable base.