Cesium carbonate → 3-(2-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)-methyl)pyrimidin-4-ylamino)propanenitrile

HRID 59166Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][C:11]#[N:12])[CH:5]=[C:4]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[N:29]1[CH:33]=[C:32]([CH3:34])[N:31]=[CH:30]1)[NH2:25].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:20][O:21][C:22]1[CH:23]=[C:24]([NH:25][C:2]2[N:7]=[C:6]([NH:8][CH2:9][CH2:10][C:11]#[N:12])[CH:5]=[C:4]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:3]=2)[CH:26]=[CH:27][C:28]=1[N:29]1[CH:33]=[C:32]([CH3:34])[N:31]=[CH:30]1

Participants

Conditions

Temperature: 120 °C

Procedure

3-(2-Chloro-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-ylamino)propanenitrile (29 mg, 0.10 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (40 mg, 0.20 mmol), cesium carbonate (64 mg, 0.20 mmol), palladium(II) acetate (3 mg, 0.01 mmol), 2-(dicyclohexylphosphino)-biphenyl (5 mg, 0.01 mmol) and dioxane (1.5 mL) were mixed in a vial and kept under an atmosphere of nitrogen. The mixture was heated in a microwave reactor at 120° C. for 90 min. The mixture was filtered through at pad of diatomeous earth. The filter plug was rinsed with MeOH. The solvents were evaporated and the residue was purified by preparative HPLC to give the title compound as a solid, 22 mg (48%).

Workup

filtrationThe mixture was filtered through at pad of diatomeous earth
washThe filter plug was rinsed with MeOH
customThe solvents were evaporated
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-503863aee99943dd809305491148e19e
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

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