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

HRID 59149Notes

Reaction equation

[N:1]1([C:5]2[CH:10]=[C:9]([CH2:11][O:12][CH2:13][C:14]([F:17])([F:16])[F:15])[N:8]=[C:7](Cl)[N:6]=2)[CH2:4][CH2:3][CH2:2]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>[N:1]1([C:5]2[CH:10]=[C:9]([CH2:11][O:12][CH2:13][C:14]([F:17])([F:16])[F:15])[N:8]=[C:7]([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:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 4-(azetidin-1-yl)-2-chloro-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine (31 mg, 0.11 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (22.37 mg, 0.11 mmol), cesium carbonate (71.7 mg, 0.22 mmol), palladium(II) acetate (3.71 mg, 0.02 mmol) and 2-(dicyclohexylphosphino)biphenyl (5.79 mg, 0.02 mmol) in dioxane (2 mL) was heated under argon at 120° C. for 90 minutes in microwave reactor. The mixture was filtered through a short silica plug which was washed with 10% methanol in ethyl acetate and the mixture was concentrated in vacuum. The residue was purified by preparative HPLC give the title compound as a dry film (41 mg, 83%).

Workup

filtrationThe mixture was filtered through a short silica plug which
washwas washed with 10% methanol in ethyl acetate
concentrationthe mixture was concentrated in vacuum
customThe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-1e186e8260d14384ab3f1ea976367a14
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

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