5-Hydroxyindole → 6-Methoxycarbonyl-7-methoxy-4-(5-indolyloxy)quinoline

HRID 1433349Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:16][CH3:17])=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[OH:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][CH:23]=[CH:22]2.C(N(C(C)C)CC)(C)C>CN1CCCC1=O>[CH3:15][O:14][C:12]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:16][CH3:17])[N:5]=[CH:4][CH:3]=[C:2]2[O:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][CH:23]=[CH:22]2)=[O:13]

Participants

Conditions

Temperature: 130 °C

Procedure

After mixing methyl 4-chloro-7-methoxyquinoline-6-carboxylate (described in WO0050405, p. 34, 8.5 g, 33.77 mmol), 5-hydroxyindole (7 g), diisopropylethylamine (8.9 ml) and N-methylpyrrolidone (8.9 ml), the mixture was heated and stirred at 130° C. for 5 hours and then at 150° C. for 8 hours. After standing to cool, the solution was adsorbed onto silica gel and purified with a silica gel column (hexane-ethyl acetate system). Ethanol, diethyl ether and hexane were added to the obtained yellow oil, and crystals precipitated after a period of standing. The crystals were filtered out, washed with diethyl ether and hexane and then dried by aspiration to obtain light yellow crystals (3.506 g, 10.06 mmol, 29.80%).

Workup

temperaturethe mixture was heated
waitat 150° C. for 8 hours
temperatureto cool
custompurified with a silica gel column (hexane-ethyl acetate system)
additionEthanol, diethyl ether and hexane were added to the obtained yellow oil, and crystals
customprecipitated after a period
filtrationThe crystals were filtered out
washwashed with diethyl ether and hexane
customdried by aspiration

Sources & evidence

ORD record: ord-cc9f5cf1288c4b4c87ea1fad05d902ca
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612092B2

Reaction notes

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