Cesium carbonate → 4-(((3,3-Difluorocyclobutyl)methoxy)methyl)-6-(1-ethoxyvinyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)pyrimidin-2-amine

HRID 59080Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([CH2:8][O:9][CH2:10][CH:11]2[CH2:14][C:13]([F:16])([F:15])[CH2:12]2)[CH:5]=[C:4]([C:17]([O:19][CH2:20][CH3:21])=[CH2:18])[N:3]=1.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][C:30]=1[N:31]1[CH:35]=[C:34]([CH3:36])[N:33]=[CH:32]1)[NH2:27].C(=O)([O-])[O-].[Cs+].[Cs+].C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:15][C:13]1([F:16])[CH2:14][CH:11]([CH2:10][O:9][CH2:8][C:6]2[CH:5]=[C:4]([C:17]([O:19][CH2:20][CH3:21])=[CH2:18])[N:3]=[C:2]([NH:27][C:26]3[CH:28]=[CH:29][C:30]([N:31]4[CH:35]=[C:34]([CH3:36])[N:33]=[CH:32]4)=[C:24]([O:23][CH3:22])[CH:25]=3)[N:7]=2)[CH2:12]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-chloro-4-(((3,3-difluorocyclobutyl)methoxy)methyl)-6-(1-ethoxyvinyl)pyrimidine (0.048 g, 0.15 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.031 g, 0.15 mmol), cesium carbonate (0.098 g, 0.30 mmol), palladium (II) acetate (5 mg, 0.02 mmol) and (2-biphenylyl)dicyclohexylphosphine (8 mg, 0.02 mmol) in dioxane (2 mL) was heated under argon at 120° C. for 90 minutes in micro wave reactor. The mixture was filtered through a short silica and was eluted with EtOAc. The residue was purified by preparative HPLC to give the title compound (0.019 g, 26.0%).

Workup

filtrationThe mixture was filtered through a short silica
washwas eluted with EtOAc
customThe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-51ef33902a784074a0d16fd96fdda5f7
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

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