Cesium carbonate → 2-(6-(1-Ethoxy-2,2-difluorocyclopropyI)-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)pyrimidin-4-yl)propan-2-ol

HRID 59180Notes

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-(2-chloro-6-(1-ethoxy-2,2-difluorocyclopropyl)pyrimidin-4-yl)propan-2-ol (8 mg, 0.03 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (6 mg, 0.03 mmol), cesium carbonate (17.81 mg, 0.05 mmol), palladium acetate (1 mg, 4 μmol) and 2-(dicyclohexylphosphino)biphenyl (1.5 mg, 4 μmol) in dioxane (1.5 mL) was heated under argon atmosphere at 120° C. for 90 minutes in microwave reactor. The crude mixture was filtered through a short silica plug which was washed with 10% MeOH in EtOAc (35 mL). The residue was purified by preparative HPLC to give the title compound as a dry film, 6 mg (48%).

Workup

filtrationThe crude mixture was filtered through a short silica plug which
washwas washed with 10% MeOH in EtOAc (35 mL)
customThe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-e83ce938d93b42dba2f3ba87db38df0d
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

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