methyl 2-((4-oxo-6-(4-(trifluoromethoxy)phenyl)quinazolin-3(4H)-yl)methyl)oxazole-4-carboxylate → 3-((4-(hydroxymethyl)oxazol-2-yl)methyl)-6-(4-(trifluoromethoxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one
Reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([O:18][C:19]([F:22])([F:21])[F:20])=[CH:14][CH:13]=3)[CH:10]=2)[N:5]=[CH:4][N:3]1[CH2:23][C:24]1[O:25][CH:26]=[C:27]([C:29](OC)=[O:30])[N:28]=1>C1COCC1>[OH:30][CH2:29][C:27]1[N:28]=[C:24]([CH2:23][N:3]2[C:2](=[O:1])[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([C:12]4[CH:13]=[CH:14][C:15]([O:18][C:19]([F:20])([F:22])[F:21])=[CH:16][CH:17]=4)[CH:10]=3)[NH:5][CH2:4]2)[O:25][CH:26]=1Participants
Reactant 1
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of methyl 2-((4-oxo-6-(4-(trifluoromethoxy)phenyl)quinazolin-3(4H)-yl)methyl)oxazole-4-carboxylate Compound 177-A (200 mg) in THF (5 mL) lithium borohydride was added (10 mg) and stirred for 1 hour. Quenched with saturated ammonium chloride and extracted with dichloromethane. Purified by gradient chromatography 0 to 5% MeOH in dichloromethane and resulting 3-((4-(hydroxymethyl)oxazol-2-yl)methyl)-6-(4-(trifluoromethoxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one Compound 177-B (130 mg) submitted into next step. 1H NMR (δ, dmso-d6, 400 MHz): 7.92 (d, 1H); 7.86 (s, 1H); 7.71 (d, 2H); 7.65 (dd, 1H); 7.38 (d, 2H); 7.03 (br s, 1H); 6.85 (d, 1H); 5.14 (t, 1H); 4.74 (s, 4H); 4.32 (d, 2H). 19F NMR (δ, dmso-d6, 376 MHz): −57.29 (s). MS m/z (ESI)=420.1 (base peak, M+H+); 861.2 (2M+Na+).
Workup
- customQuenched with saturated ammonium chloride
- extractionextracted with dichloromethane
- customPurified by gradient chromatography 0 to 5% MeOH in dichloromethane
Sources & evidence
- ORD record
- ord-1f7eae8231d44d6682be18e404aad920
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09115096B2
Reaction notes
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