4-Methoxybenzylamine → 7-(4-methoxybenzylamino)-3-(3-amino-4-fluorophenyl)-1-methyl-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one
Reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH2:8])=[CH:5][CH:4]=1.[NH2:11][C:12]1[CH:13]=[C:14]([N:19]2[CH2:24][C:23]3[CH:25]=[N:26][C:27](Cl)=[CH:28][C:22]=3[N:21]([CH3:30])[C:20]2=[O:31])[CH:15]=[CH:16][C:17]=1[F:18]>>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH:8][C:27]2[N:26]=[CH:25][C:23]3[CH2:24][N:19]([C:14]4[CH:15]=[CH:16][C:17]([F:18])=[C:12]([NH2:11])[CH:13]=4)[C:20](=[O:31])[N:21]([CH3:30])[C:22]=3[CH:28]=2)=[CH:5][CH:4]=1Participants
Conditions
- Temperature
- 180 °C
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-56cb13dd460147cb85ee66a7bde4f933
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07897762B2
Reaction notes
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