Cesium carbonate → (R)-4-(1-(4-bromo-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-6-chloro-2-methylpyrimidine

HRID 1499181Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([OH:13])[C:9]([F:12])([F:11])[F:10])=[C:4]([N:14]2[CH:18]=[CH:17][C:16]([CH3:19])=[N:15]2)[CH:3]=1.[Cl:20][C:21]1[CH:26]=[C:25](Cl)[N:24]=[C:23]([CH3:28])[N:22]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([O:13][C:25]2[CH:26]=[C:21]([Cl:20])[N:22]=[C:23]([CH3:28])[N:24]=2)[C:9]([F:12])([F:11])[F:10])=[C:4]([N:14]2[CH:18]=[CH:17][C:16]([CH3:19])=[N:15]2)[CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 1(R)-1-[4-bromo-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethanol (15.7 g, 46.3 mmol, Intermediate 1) in dioxane (200 mL) was added 4,6-dichloro-2-methylpyrimidine (30.6 g, 51 mmol) and Cs2CO3 (61.2 g, 187 mmol). The reaction mixture was heated to 80° C. for 30 h, then cooled to RT, and filtered. The residue was concentrated in vacuo and purified by normal phase column chromatography on silica gel (CH2Cl2/heptane) to provide (R)-4-(1-(4-bromo-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-6-chloro-2-methylpyrimidine as a white solid.

Workup

temperaturecooled to RT
filtrationfiltered
concentrationThe residue was concentrated in vacuo
custompurified by normal phase column chromatography on silica gel (CH2Cl2/heptane)

Sources & evidence

ORD record: ord-adb4c7d0b4534b5ba17b66205d434120
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199994B2

Reaction notes

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