Cesium carbonate → 4-[(1R)-1-[4-bromo-2-(3-methylpyrazol-1-yl)phenyl]-2,2,2-trifluoro-ethoxy]-6-chloro-pyrimidin-2-amine

HRID 1499130Notes

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.[NH2:20][C:21]1[N:26]=[C:25](Cl)[CH:24]=[C:23]([Cl: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:24]=[C:23]([Cl:28])[N:22]=[C:21]([NH2:20])[N:26]=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 (R)-1-(4-bromo-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethanol (160 mg, 0.2 mmol, Intermediate 1) in dioxane (2 mL) was added 2-amino-4,6-dichloropyrimidine (100 mg, 0.16 mmol) and Cs2CO3 (48 μg, 0.16 mmol). The reaction was heated to 80° C. for 16 h, cooled to RT, and filtered. The solvent was removed in vacuo and the residue was dissolved in a mixture of CH2Cl2 and heptane, concentrated to half the volume, filtered, and concentrated again in vacuo. Purification via normal phase silica gel chromatography (CH2Cl2/Heptane) provided 4-[(1R)-1-[4-bromo-2-(3-methylpyrazol-1-yl)phenyl]-2,2,2-trifluoro-ethoxy]-6-chloro-pyrimidin-2-amine as an off-white solid.

Workup

temperaturecooled to RT
filtrationfiltered
customThe solvent was removed in vacuo
dissolutionthe residue was dissolved in a mixture of CH2Cl2 and heptane
concentrationconcentrated to half the volume
filtrationfiltered
concentrationconcentrated again in vacuo
customPurification via normal phase silica gel chromatography (CH2Cl2/Heptane)

Sources & evidence

ORD record: ord-b60aa935f3ed43f89c20b8a4ab67c65d
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199994B2

Reaction notes

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