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

HRID 517272Notes

Reaction equation

HRID 517272 reaction equation
[H-].[Na+].[O:3]=[C:4]1[NH:13][C@H:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=2[S:22]([CH3:25])(=[O:24])=[O:23])[C:11]2[C:10](=[O:26])[CH2:9][CH2:8][CH2:7][C:6]=2[N:5]1[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=1.I[CH2:38][C:39]#[N:40]>O1CCCC1.O>[C:39]([CH2:38][N:13]1[C@H:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=2[S:22]([CH3:25])(=[O:24])=[O:23])[C:11]2[C:10](=[O:26])[CH2:9][CH2:8][CH2:7][C:6]=2[N:5]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:35])([F:36])[F:34])[CH:28]=2)[C:4]1=[O:3])#[N:40]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 69356Iodoacetonitrile3×HCID 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 86732397(S)-4-(3-(Cyanomethyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(methylsulfonyl)benzonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% in mineral oil, 11 mg, 0.28 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 tetrahydrofuran (3 mL), and the mixture is stirred at room temperature for 20 min 2-Iodoacetonitrile (7 μL, 0.10 mmol) is added, and the mixture is stirred over night. Another portion of 2-iodoaceto-nitrile (7 μL, 0.10 mmol) is added, and the mixture is stirred over night. Another portion of 2-iodoacetonitrile (14 μL, 0.20 mmol) is added, and the mixture is stirred for 2 h, diluted with water and purified by preparative HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 6 mg; ESI mass spectrum [M+H]+=529; Retention time HPLC: 1.05 min (Z018_S04).

Workup

  1. additionis added
  2. stirringthe mixture is stirred over night
  3. stirringthe mixture is stirred for 2 h
  4. custompurified by preparative HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA)
  5. custom1.05 min (Z018_S04)

Sources & evidence

ORD record
ord-226aec8eae274ecdaf1ac4a97773499a
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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