Potassium Fluoride → (1-(5-(2-Fluoro-5-hydroxyphenyl)pyrimidin-2-yl)-3-(methylsulfinyl)-1H-indol-6-yl)(morpholino)methanone

HRID 630511Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])[CH:15]=3)[C:10]([S:25]([CH3:27])=[O:26])=[CH:9]2)=[N:6][CH:7]=1.[F:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][C:30]=1B(O)O.[F-].[K+]>O1CCOCC1.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[F:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][C:30]=1[C:2]1[CH:3]=[N:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])[CH:15]=3)[C:10]([S:25]([CH3:27])=[O:26])=[CH:9]2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Bis(tri-tert-butylphosphine) palladium(0)(0.51 g, 1.0 mmol) was added under an argon atmosphere to a suspension of [1-(5-bromo-pyrimidin-2-yl)-3-methanesulfinyl-1H-indol-6-yl]-morpholin-4-yl-methanone (1.0 g, 2.0 mmol), 2-fluoro-5-hydroxyphenylboronic acid (0.625 g, 4.0 mmol) and potassium fluoride (0.29 g, 5.0 mmol) in dioxane (50 ml). The reaction mixture was stirred at 90° C. for 4 h and then filtered through a pad of celite. The filter was washed with dichloromethane (2×20 mL) and concentrated. The residue was purified by flash column chromatography [silica; dichloromethane with 2% methanol]. Light yellow solid. Yield: 0.44 g (46% of theory)

Workup

filtrationfiltered through a pad of celite
washThe filter was washed with dichloromethane (2×20 mL)
concentrationconcentrated
customThe residue was purified by flash column chromatography [silica; dichloromethane with 2% methanol]

Sources & evidence

ORD record: ord-a620be17d11646589391b85520e443a3
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315490B2

Reaction notes

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