Methyl iodide → 4-[3-Methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-3-methylsulfanyl-benzonitrile

HRID 59646Notes

Reaction equation

HRID 59646 reaction equation
CI.[O:3]=[C:4]1[NH:13][CH:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=2[S:22][CH3:23])[C:11]2[C:10](=[O:24])[CH2:9][CH2:8][CH2:7][C:6]=2[N:5]1[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=1.[C:35](=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH3:35][N:13]1[CH:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=2[S:22][CH3:23])[C:11]2[C:10](=[O:24])[CH2:9][CH2:8][CH2:7][C:6]=2[N:5]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=2)[C:4]1=[O:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonate2×HCID 1186929024-[2,5-Dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-3-methylsulfanyl-benzonitrile2×

Product 1

HCID 1186929224-[3-Methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-3-methylsulfanyl-benzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Methyliodide (70 μL, 1.10 mmol) is added to a mixture of 4-[2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-3-methylsulfanyl-benzonitrile (INTERMEDIATE 6; 177 mg; 0.354 mmol) and cesium carbonate (300 mg, 0.921 mmol) in DMF (2.4 mL) and the mixture is stirred at room temperature for 2 h. During the reaction, more cesium carbonate is added in small portions (total of 700 mg; 2.15 mmol). The reaction mixture is filtered and the filtrate is purified by reversed phase HPLC (Sunfire, gradient of acetonitrile in water, 0.1% TFA). Yield: 26 mg. ESI mass spectrum: [M+H]+=472; Retention time HPLC: 1.10 min (Z018_S04).

Workup

  1. additionis added in small portions (total of 700 mg; 2.15 mmol)
  2. filtrationThe reaction mixture is filtered
  3. customthe filtrate is purified by reversed phase HPLC (Sunfire, gradient of acetonitrile in water, 0.1% TFA)
  4. custom1.10 min (Z018_S04)

Sources & evidence

ORD record
ord-d76847758d1b42cc926c6dc9c909a98f
Source dataset
uspto-grants-2016_09
Patent number
US09440930B2

Reaction notes

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