Methanol → HCID 178492956, compound

HRID 1067939Notes

Reaction equation

[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([I:21])=[CH:15][C:14]=3F)=[O:9])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:27][OH:28].[Cl-].[NH4+]>CN(C=O)C>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([I:21])=[CH:15][C:14]=3[O:28][CH3:27])=[O:9])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 135 °C

Procedure

N-(4-Chlorobenzyl)-8-fluoro-4-hydroxy-6-iodo-3-quinolinecarboxamide (2.95 g) from Preparation No. 1 and sodium hydride (60% dispersion, 520 mg) is suspended in DMF (60 mL) and to the mixture is added methanol (288 μL). After being heated for 1 h at 135° C., additional sodium hydride (200 mg) is added, and the mixture is heated for an additional 1 h. The reaction mixture is allowed to cool to rt and then is poured into saturated aqueous ammonium chloride (200 mL). The resulting precipitate is filtered and washed with water (20 mL), tert-butyl methyl ether (20 mL), and heptane (20 mL). The crude product is purified by column chromatography (heptane/2-propanol, 9/1; 4/1) to afford 1.68 g (56%) of the title compound as a white solid. Recrystallization (acetic acid, water) affords a hydrate (1H2O).

Workup

temperaturethe mixture is heated for an additional 1 h
temperatureto cool to rt
filtrationThe resulting precipitate is filtered
washwashed with water (20 mL), tert-butyl methyl ether (20 mL), and heptane (20 mL)
customThe crude product is purified by column chromatography (heptane/2-propanol, 9/1; 4/1)

Sources & evidence

ORD record: ord-d7a98dc3c78747d29b13620e8356e6e8
Source dataset: uspto-grants-2001_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06248739B1

Reaction notes

Loading…