Dichloromethane → US9290457, Example 16

HRID 927019Notes

Reaction equation

HRID 927019 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].[CH3:32][N:33]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[CH:35][C:34]1=[O:48].C(=O)([O-])[O-].[K+].[K+].ClCCl>C(#N)C>[C:1]([C:4]1[C@@H:5]([C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=2[C:37]2[CH:36]=[CH:35][C:34](=[O:48])[N:33]([CH3:32])[CH:38]=2)[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]

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 11430Potassium CarbonateHCID 454801941-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one2×HCID 1186916864-[5-Acetyl-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidin-4-yl]-3-bromo-benzonitrile2×

Product 1

HCID 118691668US9290457, Example 16

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

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)(400 mg, 0.81 mmol) and N-methyl-1H-pyridin-2-one-5-boronic acid pinacol ester (248 mg, 1.06 mmol) are suspended in acetonitrile (15 mL) and are degassed with a stream of argon. Potassium carbonate solution (2 mol/L, 1.22 mL, 2.44 mmol) and 1.1-bis(diphenylphosphino)-ferrocendichloro-palladium(II), complex with dichloromethane (1:1) (6.34 mg, 0.008 mmol) are added and the reaction is stirred at 100° C. overnight. Additional N-methyl-1H-pyridin-2-one-5-boronic acid pinacol ester (100 mg, 0.4 mmol) and 1.1-bis(diphenylphosphino)-ferrocendichloropalladium(II), complex with dichloromethane (1:1) (2 mg, 0.002 mmol) are added and the reaction is continued at 120° C. for 60 min under microwave irradiation. The reaction mixture is filtrated over a layer of silica gel and basic aluminum oxide 1:1 and purified by reversed phase HPLC. Yield: 125 mg; ESI mass spectrum [M+H]+=521; Retention time HPLC: 1.01 min (HPLC method Z018_S04).

Workup

  1. customare degassed with a stream of argon
  2. customthe reaction is continued at 120° C. for 60 min under microwave irradiation
  3. filtrationThe reaction mixture is filtrated over a layer of silica gel and basic aluminum oxide 1:1
  4. custompurified by reversed phase HPLC
  5. custom1.01 min (HPLC method Z018_S04)

Sources & evidence

ORD record
ord-11595c6ae5e649b3ab7aa0df6590a1f8
Source dataset
uspto-grants-2016_03
Patent number
US09290457B2

Reaction notes

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