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

HRID 59158Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][CH3:9])[CH:5]=[C:4]([CH2:10][O:11][CH2:12][CH:13]2[CH2:15][CH2:14]2)[N:3]=1.[CH3:16][O:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][C:24]=1[N:25]1[CH:29]=[C:28]([CH3:30])[N:27]=[CH:26]1)[NH2:21].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>[CH:13]1([CH2:12][O:11][CH2:10][C:4]2[N:3]=[C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:24]([N:25]4[CH:29]=[C:28]([CH3:30])[N:27]=[CH:26]4)=[C:18]([O:17][CH3:16])[CH:19]=3)[N:7]=[C:6]([NH:8][CH3:9])[CH:5]=2)[CH2:15][CH2:14]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-chloro-6-((cyclopropylmethoxy)methyl)-N-methylpyrimidin-4-amine (41 mg, 0.18 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (73 mg, 0.36 mmol), cesium carbonate (117 mg, 0.36 mmol), palladium acetate (6 mg, 0.03 mmol) and 2-(dicyclohexyl-phosphino)biphenyl (9 mg, 0.03 mmol) was stirred under argon at 120° C. for 90 minutes in microwave oven. The mixture was filtered through a short silica gel plug which was washed with 10% solution of methanol in ethyl acetate (75 mL). The eluate was concentrated and the residue was purified by preparative HPLC to give the title compound as a dry film (30 mg, 42%).

Workup

filtrationThe mixture was filtered through a short silica gel plug which
washwas washed with 10% solution of methanol in ethyl acetate (75 mL)
concentrationThe eluate was concentrated
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-02c8479d3b5542c9a7d3b0fe598a1b0a
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

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