Methylamine → HCID 67063033, compound
Reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][C:13]3[CH:15]=[N:16][C:17](Cl)=[CH:18][C:12]=3[N:11]([C:20]([CH3:23])([CH3:22])[CH3:21])[C:10]2=[O:24])[CH:5]=[CH:6][C:7]=1[F:8].[CH3:25][NH2:26]>[Cu]I>[NH2:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][C:13]3[CH:15]=[N:16][C:17]([NH:26][CH3:25])=[CH:18][C:12]=3[N:11]([C:20]([CH3:23])([CH3:22])[CH3:21])[C:10]2=[O:24])[CH:5]=[CH:6][C:7]=1[F:8]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 180 °C
Procedure
3-(3-Amino-4-fluorophenyl)-1-tert-butyl-7-chloro-3,4-dihydro-1H-pyrido[4,3-d]pyrimidin-2-one (2.0 g, 5.7 mmol), CuI (200 mg, 1.05 mmol) and methylamine (200 mL) were combined in a steel bomb and heated to 180° C. for 48 h. The reaction vessel was cooled to −78° C., unsealed, and warmed to RT. The reaction was partitioned between EtOAc and H2O, and the aqueous layer was extracted with EtOAc. The combined organics were washed with brine (2×100 mL), dried (Na2SO4), concentrated and purified by neutral aluminum oxide column chromatography to provide 3-(3-amino-4-fluorophenyl)-1-tert-butyl-7-(methylamino)-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one (900 mg, 46% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.76 (s, 1 H), 6.91 (dd, J=11.1, 8.7 Hz, 1 H), 6.61 (dd, J=8.1, 2.4 Hz, 1 H), 6.35-6.32 (m, 3 H), 5.14 (s, 2 H), 4.29 (s, 2 H), 2.74 (d, J=4.8 Hz, 3 H), 1.55 (s, 9 H); MS (ESI) m/z: 344.0 [M+H]+.
Workup
- temperatureThe reaction vessel was cooled to −78° C.
- temperatureunsealed, and warmed to RT
- customThe reaction was partitioned between EtOAc and H2O
- extractionthe aqueous layer was extracted with EtOAc
- washThe combined organics were washed with brine (2×100 mL)
- dry with materialdried (Na2SO4)
- concentrationconcentrated
- custompurified by neutral aluminum oxide column chromatography
Sources & evidence
- ORD record
- ord-128c885e0ca54739bf7a4fa0f63e4325
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07897762B2
Reaction notes
Loading…