Ammonium Chloride → 3-(3-amino-4-fluorophenyl)-7-chloro-1-methyl-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one
Reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[CH2:8][N:7]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14]([N+:19]([O-])=O)[CH:13]=3)[C:6](=[O:22])[N:5]([CH3:23])[C:4]=2[CH:3]=1.[NH4+].[Cl-]>CO.C1COCC1.[Zn]>[NH2:19][C:14]1[CH:13]=[C:12]([N:7]2[CH2:8][C:9]3[CH:10]=[N:11][C:2]([Cl:1])=[CH:3][C:4]=3[N:5]([CH3:23])[C:6]2=[O:22])[CH:17]=[CH:16][C:15]=1[F:18]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Procedure
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.
Sources & evidence
- ORD record
- ord-3f4a9ab35b94434da9e39723a01eddb3
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07897762B2
Reaction notes
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