N-methyl-2-pyrrolidone → 6-Carbamoyl-4-(1H-indol-5-yloxy)-7-methoxyquinoline

HRID 387877Notes

Reaction equation

[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[CH:9][CH:8]=[C:7]2Cl)(=[O:3])[NH2:2].[OH:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[NH:23][CH:22]=[CH:21]2.C(N(C(C)C)CC)(C)C.CN1CCCC1=O>CS(C)=O>[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[CH:9][CH:8]=[C:7]2[O:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[NH:23][CH:22]=[CH:21]2)(=[O:3])[NH2:2]

Participants

Conditions

Temperature: 150 °C

Procedure

After mixing 6-carbamoyl-4-chloro-7-methoxyquinoline (2.0 g, 8.4509 mmol), 5-hydroxyindole (1.68 g), diisopropylethylamine (2.2 ml) and N-methylpyrrolidone (2.2 ml), the mixture was heated and stirred at 150° C. for 5 hours. After cooling, the solidified part of the reaction solution was dissolved in dimethylsulfoxide and then adsorbed onto NH silica gel and purified by NH silica gel column chromatography (ethyl acetate-methanol system). The obtained crystals were suspended in ethanol, the suspension was diluted with diethyl ether and hexane, and the crystals were filtered out, washed with diethyl ether:hexane=1:5 and dried by aspiration to obtain the title compound (1.291 g, 3.8698 mmol, 45.79%) as light yellow crystals.

Workup

temperaturethe mixture was heated
temperatureAfter cooling
custompurified by NH silica gel column chromatography (ethyl acetate-methanol system)
additionthe suspension was diluted with diethyl ether and hexane
filtrationthe crystals were filtered out
washwashed with diethyl ether
dry with materialhexane=1:5 and dried by aspiration

Sources & evidence

ORD record: ord-546eb722e2aa4de597cd3ef4baaad790
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08372981B2

Reaction notes

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