Butyl iodide → 4-(3-Butyl-1-(3-(trifluoromethyl)phenyl)-2,5-dioxo-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)benzonitrile
Reaction equation
C([N-]C(C)C)(C)C.[Li+].[O:9]=[C:10]1[NH:19][CH:18]([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=2)[C:17]2[C:16](=[O:28])[CH2:15][CH2:14][CH2:13][C:12]=2[N:11]1[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=1.[CH2:39](I)[CH2:40][CH2:41][CH3:42]>CN(C)C=O>[CH2:39]([N:19]1[CH:18]([C:20]2[CH:21]=[CH:22][C:23]([C:24]#[N:25])=[CH:26][CH:27]=2)[C:17]2[C:16](=[O:28])[CH2:15][CH2:14][CH2:13][C:12]=2[N:11]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:36])[F:37])[CH:30]=2)[C:10]1=[O:9])[CH2:40][CH2:41][CH3:42]Participants
5
Procedure
Lithium diisopropylamide (2.0 M in tetrahydrofuran, 135 μL, 0.27 mmol) is added at 0° C. to a solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-benzonitrile (example 1, 100 mg, 0.243 mmol) in N,N-dimethylformamide (5 mL). n-Butyl iodide (30 μL, 0.264 mmol) is added, and the mixture is warmed to room temperature and stirred for 2 h. Another portion of n-Butyl iodide (15 μL, 0.132 mmol) is added and the mixture is stirred over night and purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 28 mg; ESI mass spectrum [M+H]+=468; Retention time HPLC: 1.47 min (V001—006).
Workup
- stirringthe mixture is stirred over night
- custompurified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA)
- custom1.47 min (V001—006)
Sources & evidence
- ORD record
- ord-c7268424efea4bc297790bf7f32a8d36
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09115093B2
Reaction notes
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