Dichloromethane → US9290457, Example 17

HRID 927020Notes

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]=[CH:37][C:36](B(O)O)=[CH:35][C:34]1=[O:42].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:36]2[CH:37]=[CH:38][N:33]([CH3:32])[C:34](=[O:42])[CH:35]=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

Conditions

Temperature: 75 °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)(300 mg, 0.61 mmol) and (1-methyl-2-oxo-4-pyridyl)boronic acid (121 mg, 0.79 mmol) are suspended in acetonitrile (9 mL) and are degassed with a stream of argon. Potassium carbonate solution (2 mol/L, 914 μL, 1.83 mmol) and 1.1-bis(diphenylphosphino)-ferrocendichloropalladium(II), complex with dichloromethane (1:1) (9.95 mg, 0.012 mmol) are added and the reaction is shaken at 75° C. overnight. The reaction mixture is filtrated over a layer of silica gel and basic aluminum oxide 1:1 and purified by reversed phase HPLC. Yield: 142 mg; ESI mass spectrum [M+H]+=521; Retention time HPLC: 0.99 min (HPLC method Z018_S04).

Workup

customare degassed with a stream of argon
filtrationThe reaction mixture is filtrated over a layer of silica gel and basic aluminum oxide 1:1
custompurified by reversed phase HPLC
custom0.99 min (HPLC method Z018_S04)

Sources & evidence

ORD record: ord-4e8ae0ba6d324dc9a0b6185c5ca5473a
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290457B2

Reaction notes

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