Dichloromethane → 1-(2,6-dichlorophenyl)-3-[6-methoxy-7-(N-methylpiperidin-4-ylmethoxy)quinazolin-4-yl]urea
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]=[C:10]=[O:11].[NH2:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:25][CH:26](C)[CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1.[CH2:34](Cl)Cl>CN(C=O)C.CO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[NH:9][C:10]([NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:25][CH2:26][CH:27]3[CH2:28][CH2:29][N:30]([CH3:34])[CH2:31][CH2:32]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1)=[O:11]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
2,6-Dichlorophenyl isocyanate (0.075 g) was added to a solution of 4-amino-6-methoxy-7-(methylpiperidin-4-ylmethoxy)quinazoline (0.093 g) in a mixture of methylene chloride (2 ml) and DMF (0.1 ml) and the reaction mixture was stirred at ambient temperature for 16 hours. The resultant solid was isolated, redissolved in a 20:1 mixture of methylene chloride and methanol and purified by column chromatography on silica using increasingly polar mixtures of methylene chloride, methanol and a 1% aqueous ammonium hydroxide solution as eluent. There was thus obtained the title compound as a white solid (0.029 g); NMR Spectrum: (DMSOd6) 1.3-1.4 (m, 2H), 1.7-1.8 (m, 4H), 1.85 (t, 1H), 2.1 (s, 3H), 2.8 (d, 2H), 3.9 (s, 3H), 4.0 (br d, 2H), 7.3 (br s, 1H), 7.4 (d, 1H), 7.5 (s, 1H), 7.6 (s, 1H), 8.0 (br s, 1H), 8.7 (s, 1H); Mass Spectrum: M+H+ 490, 492 and 494.
Workup
- customThe resultant solid was isolated
- custompurified by column chromatography on silica using
- temperatureincreasingly polar mixtures of methylene chloride, methanol
Sources & evidence
- ORD record
- ord-ba9dc2bcc3ee4adba2547c59da45f611
- Source dataset
- uspto-grants-2004_10
- Patent number
- US06806274B1
Reaction notes
Loading…