Cesium carbonate → 4-(4,4-Difluoropiperidin-1-yl)-N-(3-methoxy-4-(6-methylpyridazin-4-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

HRID 59151

Reaction equation

Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][C:11]([F:15])([F:14])[CH2:10][CH2:9]2)[CH:5]=[C:4]([CH2:16][O:17][CH2:18][C:19]([F:22])([F:21])[F:20])[N:3]=1.[CH3:23][O:24][C:25]1[CH:26]=[C:27]([CH:29]=[CH:30][C:31]=1[C:32]1[CH:37]=[C:36]([CH3:38])[N:35]=[N:34][CH:33]=1)[NH2:28].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>[F:14][C:11]1([F:15])[CH2:12][CH2:13][N:8]([C:6]2[CH:5]=[C:4]([CH2:16][O:17][CH2:18][C:19]([F:22])([F:21])[F:20])[N:3]=[C:2]([NH:28][C:27]3[CH:29]=[CH:30][C:31]([C:32]4[CH:37]=[C:36]([CH3:38])[N:35]=[N:34][CH:33]=4)=[C:25]([O:24][CH3:23])[CH:26]=3)[N:7]=2)[CH2:9][CH2:10]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-chloro-4-(4,4-difluoropiperidin-1-yl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine (40 mg, 0.12 mmol), 3-methoxy-4-(6-methylpyridazin-4-yl)aniline (25 mg, 0.12 mmol), cesium carbonate (75 mg, 0.23 mmol), palladium(II) acetate (4 mg, 0.02 mmol) and 2-(dicyclohexylphosphino)biphenyl (6 mg, 0.02 mmol) in dioxane (2 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) and the eluate was concentrated in vacuum. The residue was purified by preparative HPLC to give the title compound as a solid, 35 mg (58%).

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-d34d6ade3ddc4011a1057bfd59a5a48f
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Linked notes

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