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

HRID 59154Notes

Reaction equation

[CH2:1]([N:8]([CH3:23])[C:9]1[CH:14]=[C:13]([CH2:15][O:16][CH2:17][C:18]([F:21])([F:20])[F:19])[N:12]=[C:11](Cl)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH:30]=[CH:31][C:32]=1[N:33]1[CH:37]=[C:36]([CH3:38])[N:35]=[CH:34]1)[NH2:29].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>[CH2:1]([N:8]([CH3:23])[C:9]1[CH:14]=[C:13]([CH2:15][O:16][CH2:17][C:18]([F:21])([F:20])[F:19])[N:12]=[C:11]([NH:29][C:28]2[CH:30]=[CH:31][C:32]([N:33]3[CH:37]=[C:36]([CH3:38])[N:35]=[CH:34]3)=[C:26]([O:25][CH3:24])[CH:27]=2)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of N-benzyl-2-chloro-N-methyl-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-amine (197 mg, 0.57 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (116 mg, 0.57 mmol), cesium carbonate (371 mg, 1.14 mmol), palladium (II) acetate (19 mg, 0.09 mmol) and 2-(dicyclohexylphosphino)biphenyl (30 mg, 0.09 mmol) in dioxane (4 mL) was heated under argon at 120° C. for 90 minutes in a microwave reactor. 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 in vacuum and the residue was purified by preparative HPLC to give the title compound as a solid 194 mg (66%).

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 in vacuum
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-447b51f5fdd943a4aa05f583146aed56
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

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