Cesium carbonate → N2-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-N4-(oxetan-3-yl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine-2,4-diamine

HRID 59163Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][C:9]=1[N:10]1[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11]1)[NH2:6].Cl[C:17]1[N:22]=[C:21]([NH:23][CH:24]2[CH2:27][O:26][CH2:25]2)[CH:20]=[C:19]([CH2:28][O:29][CH2:30][C:31]([F:34])([F:33])[F:32])[N:18]=1.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>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:6][C:17]2[N:22]=[C:21]([NH:23][CH:24]3[CH2:27][O:26][CH2:25]3)[CH:20]=[C:19]([CH2:28][O:29][CH2:30][C:31]([F:33])([F:34])[F:32])[N:18]=2)[CH:7]=[CH:8][C:9]=1[N:10]1[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (78 mg, 0.38 mmol), 2-chloro-N-(oxetan-3-yl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-amine (57 mg, 0.19 mmol), cesium carbonate (125 mg, 0.38 mmol), palladium(II) acetate (6.45 mg, 0.03 mmol) and 2-(dicyclohexylphosphino)biphenyl (10.07 mg, 0.03 mmol) in dioxane (1 mL) was heated at 120° C. by microwave irradiation under nitrogen atmosphere for 90 minutes. The mixture was filtered through diatomeous earth and the filter pad was washed with methanol. The eluate was concentrated in vacuum and purified by preparative chromatography yielding the title compound as a solid 45 mg (51%).

Workup

filtrationThe mixture was filtered through diatomeous earth
washthe filter pad was washed with methanol
concentrationThe eluate was concentrated in vacuum
custompurified by preparative chromatography

Sources & evidence

ORD record: ord-84ede42561f241749e8ff785318eb49f
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

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