Cesium carbonate → 4-((Cyclopropylmethoxy)methyl)-6-(1-ethoxyvinyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)pyrimidin-2-amine

HRID 59119Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([CH2:8][O:9][CH2:10][CH:11]2[CH2:13][CH2:12]2)[CH:5]=[C:4]([C:14]([O:16][CH2:17][CH3:18])=[CH2:15])[N:3]=1.[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][C:27]=1[N:28]1[CH:32]=[C:31]([CH3:33])[N:30]=[CH:29]1)[NH2:24].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:11]1([CH2:10][O:9][CH2:8][C:6]2[CH:5]=[C:4]([C:14]([O:16][CH2:17][CH3:18])=[CH2:15])[N:3]=[C:2]([NH:24][C:23]3[CH:25]=[CH:26][C:27]([N:28]4[CH:32]=[C:31]([CH3:33])[N:30]=[CH:29]4)=[C:21]([O:20][CH3:19])[CH:22]=3)[N:7]=2)[CH2:13][CH2:12]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-chloro-4-((cyclopropylmethoxy)methyl)-6-(1-ethoxyvinyl)pyrimidine (88 mg, 0.33 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (67 mg, 0.33 mmol), cesium carbonate (213 mg, 0.65 mmol), palladium acetate (11 mg, 0.05 mmol) and 2-(dicyclohexylphosphino)biphenyl (17 mg, 0.05 mmol) in dioxane (2 mL) were heated under argon atmosphere at 120° C. for 90 minutes in microwave reactor. The mixture was filtered through a short silica plug which was washed with 10% MeOH in EtOAc. The solvents were evaporated and the residue was purified by preparative to give the title compound 98 mg (69%).

Workup

filtrationThe mixture was filtered through a short silica plug which
washwas washed with 10% MeOH in EtOAc
customThe solvents were evaporated
customthe residue was purified by preparative

Sources & evidence

ORD record: ord-0483668d06a040b59a4a16dfb194b87c
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

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