1,5,6,7-Tetrahydro-4H-indol-4-one → 1-[2-Hydroxy-4-methyl-4-(5-pyrimidin-5-yl-2,3-dihydrobenzofuran-7-yl)-2-trifluoromethylpentyl]-1,5,6,7-tetrahydroindol-4-one

HRID 400693Notes

Reaction equation

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

Participants

Conditions

Temperature: 85 °C

Procedure

To a suspension of 5-{7-[1,1-dimethyl-2-(2-trifluoromethyloxiranyl)ethyl]-2,3-dihydrobenzofuran-5-yl}pyrimidine (56.0 mg, 0.15 mmol) and 1,5,6,7-tetrahydroindol-4-one (41.6 mg, 0.31 mmol) in 1.0 mL of anhydrous ethanol was added sodium ethoxide solution (0.057 mL, 21 wt. % in ethanol). The reaction mixture was heated at 85° C. for 15 hours. After cooling to room temperature, the reaction mixture was concentrated onto silica gel (for dry loading) and purified by silica gel chromatography (eluted with 40% to 70% ethyl acetate-hexanes) to give 42.0 mg (55% yield) of the title compound as a white solid, m.p. 213° C.-214° C.

Workup

temperatureAfter cooling to room temperature
concentrationthe reaction mixture was concentrated onto silica gel (for dry loading)
custompurified by silica gel chromatography (eluted with 40% to 70% ethyl acetate-hexanes)

Sources & evidence

ORD record: ord-eb18caaab4314294b42070f5baa2a717
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08741897B2

Reaction notes

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