1-(1-(5-(2-Fluorophenyl)pyrimidin-2-yl)-6-(morpholine-4-carbonyl)-1H-indol-3-yl) ethanone → (1-(5-(2-Fluorophenyl)pyrimidin-2-yl)-3-(2-hydroxypropan-2-yl)-1H-indol-6-yl)(morpholino)methanone

HRID 630495Notes

Reaction equation

[CH3:1][Mg]I.[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:12]=[N:13][C:14]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]([N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[O:27])[CH:24]=3)[C:19]([C:34](=[O:36])[CH3:35])=[CH:18]2)=[N:15][CH:16]=1>C1COCC1>[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:16]=[N:15][C:14]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]([N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)=[O:27])[CH:24]=3)[C:19]([C:34]([OH:36])([CH3:1])[CH3:35])=[CH:18]2)=[N:13][CH:12]=1

Participants

Conditions

Temperature: -30 °C

Procedure

Methyl magnesium iodide (3M solution in diethyl ether, 0.14 mL, 0.439 mmol, 1.5 eq) was added at −50° C. to a stirred solution of 184a) (130 mg, 0.292 mmol, 1.0 eq) in dry THF (10 mL). The reaction mixture was stirred for 2 h at −30° C., then quenched with ammonium chloride solution, diluted with water (20 mL) and extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated. The remnant was purified by preparative TLC using ethyl acetate/pet ether (7:3) as eluent. White solid. Yield: 50 mg (37% of theory).

Workup

customquenched with ammonium chloride solution
additiondiluted with water (20 mL)
extractionextracted with ethyl acetate (2×20 mL)
washThe combined organic layers were washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe remnant was purified by preparative TLC

Sources & evidence

ORD record: ord-16d0ec9bc3984797acd5c410ba2d10db
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315490B2

Reaction notes

Loading…