Water → (S)-4-(3-Methyl-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(methylsulfonyl)benzonitrile

HRID 517264Notes

Reaction equation

HRID 517264 reaction equation
[CH:1]([N-]C(C)C)(C)C.[Li+].[O:9]=[C:10]1[NH:19][C@H:18]([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][C:21]=2[S:28]([CH3:31])(=[O:30])=[O:29])[C:17]2[C:16](=[O:32])[CH2:15][CH2:14][CH2:13][C:12]=2[N:11]1[C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=1.CI.O>CN(C)C=O>[CH3:1][N:19]1[C@H:18]([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][C:21]=2[S:28]([CH3:31])(=[O:30])=[O:29])[C:17]2[C:16](=[O:32])[CH2:15][CH2:14][CH2:13][C:12]=2[N:11]([C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:41])([F:42])[F:40])[CH:34]=2)[C:10]1=[O:9]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 86270877(S)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(methylsulfonyl)benzonitrile

Product 1

HCID 86270876(S)-4-(3-Methyl-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(methylsulfonyl)benzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Lithium diisopropylamide (1.8 M in tetrahydrofuran, 62 μL, 0.11 mmol) is added to a solution of (S)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(methylsulfonyl)benzonitrile (example 18A, 50 mg, 0.10 mmol) in N,N-dimethylformamide (1 mL). Methyl iodide (8 μL, 0.13 mmol) is added and the mixture is stirred for 1 h. Water is added and the mixture is purified by reversed phase HPLC (Agilent ZORBAX™ SB-C18, gradient of acetonitrile in water, 0.15% formic acid). Yield: 20 mg; ESI mass spectrum [M+H]+=504; Retention time HPLC: 1.04 min (Z017_S04).

Workup

  1. customthe mixture is purified by reversed phase HPLC (Agilent ZORBAX™ SB-C18, gradient of acetonitrile in water, 0.15% formic acid)
  2. custom1.04 min (Z017_S04)

Sources & evidence

ORD record
ord-fb4500a9909d409ab5fc75c88f97d807
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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