Ammonium Chloride → 3-(3-amino-4-fluorophenyl)-7-chloro-1-methyl-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one

Participants

Reaction Steps

By analogy to Example A24, 6-chloro-4-(methylamino)nicotinaldehyde (from Example A24), 4-fluoro-3-nitroaniline and sodium triacetoxy borohydride are combined in glacial acetic acid to give crude 2-chloro-5-((4-fluoro-3-nitrophenylamino)methyl)-N-methylpyridin-4-amine, which is reacted with diphosgene by the procedure of Example A75 to give 7-chloro-3-(4-fluoro-3-nitrophenyl)-1-methyl-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one. Zn Dust is reacted with a suspension of 7-chloro-3-(4-fluoro-3-nitrophenyl)-1-methyl-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one and NH4Cl in MeOH/THF (1:1) to provide 3-(3-amino-4-fluorophenyl)-7-chloro-1-methyl-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one. By analogy to Example A25, 4-methoxybenzylamine and 3-(3-amino-4-fluorophenyl)-7-chloro-1-methyl-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one are combined and heated to 180° C. to provide 7-(4-methoxybenzylamino)-3-(3-amino-4-fluorophenyl)-1-methyl-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one, which is further reacted with trifluoroacetic acid to provide 7-amino-3-(3-amino-4-fluorophenyl)-1-methyl-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one.

Provenance & Evidence