Dichloromethane → US9290457, Intermediate 5

HRID 927001Notes

Reaction equation

HRID 927001 reaction equation
[C:1]([C:4]1[CH:5]([C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=2Br)[N:6]([CH3:22])[C:7](=[O:21])[N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[C:9]=1[CH3:10])(=[O:3])[CH3:2].Cl[CH2:33]Cl.[C:35]([O-:38])(=[O:37])C.[Na+].[C]=O>CO>[CH3:33][O:38][C:35](=[O:37])[C:24]1[CH:25]=[C:26]([C:27]#[N:28])[CH:29]=[CH:30][C:23]=1[CH:5]1[C:4]([C:1](=[O:3])[CH3:2])=[C:9]([CH3:10])[N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:18])[F:19])[CH:12]=2)[C:7](=[O:21])[N:6]1[CH3:22]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 517045Sodium AcetateHCID 1186916864-[5-Acetyl-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidin-4-yl]-3-bromo-benzonitrile2×HCID 178418416HCID 178418416, compound

Product 1

HCID 118691667US9290457, Intermediate 5

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-[5-Acetyl-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidin-4-yl]-3-bromo-benzonitrile (intermediate 4)(643.0 mg, 1.31 mmol), 1.1-bis(diphenyl-phosphino)-ferrocendichloropalladium(II), complex with dichloromethane (1:1) (51.5 mg, 0.06 mmol) and sodium acetate (327.5 mg, 4.0 mmol) are suspended in methanol (21 mL) and treated with carbon monoxide at 5 bar and 100° C. for 19 h. The reaction mixture is concentrated, water and ethyl acetate are added and the phases are separated. The organic phase is washed twice with water, dried over MgSO4 and concentrated. Yield: 671 mg. ESI mass spectrum: [M+H]+=472; Retention time HPLC: 1.12 min (HPLC method Z018_S04).

Workup

  1. concentrationThe reaction mixture is concentrated
  2. additionwater and ethyl acetate are added
  3. customthe phases are separated
  4. washThe organic phase is washed twice with water
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. custom1.12 min (HPLC method Z018_S04)

Sources & evidence

ORD record
ord-74f6f7cb76db401683171020d4514395
Source dataset
uspto-grants-2016_03
Patent number
US09290457B2

Reaction notes

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