Potassium Carbonate → 2-Fluoro-5-(2-(2-(4-fluorophenyl)-2-methylpropylamino)pyrimidin-5-yl)benzonitrile

HRID 1853114Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][CH2:9][C:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)([CH3:12])[CH3:11])=[N:6][CH:7]=1.[C:20]([C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][C:27]=1[F:28])#[N:21].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[F:28][C:27]1[CH:26]=[CH:25][C:24]([C:2]2[CH:3]=[N:4][C:5]([NH:8][CH2:9][C:10]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)([CH3:12])[CH3:11])=[N:6][CH:7]=2)=[CH:23][C:22]=1[C:20]#[N:21]

Participants

Conditions

Temperature: 120 °C

Procedure

To a 5 mL microwave reaction vessel was added 5-bromo-N-(2-(4-fluorophenyl)-2-methylpropyl)pyrimidin-2-amine (267 mg, 0.8 mmol, 1.0 equiv), 3-cyano-4-fluorophenylboronic acid (203 mg, 1.2 mmol, 1.5 equiv), Cl2Pd(dppf) (60 mg, 82 μmol, 0.1 equiv), potassium carbonate (1.2 mL of a 2N aqueous solution, 2.4 mmol, 3.0 equiv), and dioxane (4 mL). The reaction was heated in a microwave reactor at 120° C. for 20 min. The aqueous layer was removed from the reaction, and the organic layer was directly purified by reverse phase column chromatography to give 220 mg (73%) of 2-fluoro-5-(2-(2-(4-fluorophenyl)-2-methylpropylamino)pyrimidin-5-yl)benzonitrile as a white solid.

Workup

customThe aqueous layer was removed from the reaction
customthe organic layer was directly purified by reverse phase column chromatography

Sources & evidence

ORD record: ord-cd74637a6db1458c8f25845e804eda0e
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962632B2

Reaction notes

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