Ethyl orthoformate → 4-chloro-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinoline

HRID 606104Notes

Reaction equation

[CH:1](OCC)(OCC)OCC.[Cl:11][C:12]1[C:21]([NH2:22])=[C:20]([NH:23][CH2:24][C:25]2[O:29][N:28]=[C:27]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[CH:26]=2)[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]=1>C1(C)C=CC=CC=1.Cl.N1C=CC=CC=1>[Cl:11][C:12]1[C:21]2[N:22]=[CH:1][N:23]([CH2:24][C:25]3[O:29][N:28]=[C:27]([C:30]4[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=4)[CH:26]=3)[C:20]=2[C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N:13]=1

Participants

Conditions

Temperature: 110 °C

Procedure

Pyridine hydrochloride (3 mg, 0.02 mmol) and triethyl orthoformate (0.3 mL, 1.7 mmol) were added to a solution of 2-chloro-N4-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}quinoline-3,4-diamine (0.4294 g, 1.164 mmol) in toluene (10 mL), and the reaction was heated at 110° C. for 16 hours. A solid was present and was isolated by filtration. The filtrate was concentrated under reduced pressure and triturated with diethyl ether to provide a solid. The two solids were combined and purified by column chromatography on silica gel (eluting with 1:1 ethyl acetate:hexane) to provide 0.259 g of 4-chloro-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinoline as a white solid, mp 219.0-220.0° C.

Workup

customwas isolated by filtration
concentrationThe filtrate was concentrated under reduced pressure
customtriturated with diethyl ether
customto provide a solid
custompurified by column chromatography on silica gel (eluting with 1:1 ethyl acetate:hexane)

Sources & evidence

ORD record: ord-e52e5badcbd247e1861133d8feb06cd9
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07915281B2

Reaction notes

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