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

HRID 59161Notes

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

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (99 mg, 0.49 mmol), 2-chloro-N-(cyclopropylmethyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-amine (72 mg, 0.24 mmol), cesium carbonate (159 mg, 0.49 mmol), palladium(II) acetate (8.20 mg, 0.04 mmol) and 2-(dicyclohexylphosphino)biphenyl (12.80 mg, 0.04 mmol) in dioxane (1.5 mL) was heated at 120° C. by microwave irradiation under nitrogen atmosphere for 90 minutes. The mixture was filtered through diatomeous earth, the pad was eluted with methanol. The eluate was concentrated and the residue was purified by preparative chromatography to give the title compound as a dry film, 65 mg (58%).

Workup

filtrationThe mixture was filtered through diatomeous earth
washthe pad was eluted with methanol
concentrationThe eluate was concentrated
customthe residue was purified by preparative chromatography

Sources & evidence

ORD record: ord-b2fc31521de7494ea7f4779117991f01
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

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