5-Methyl-3-phenyl-4-isoxazolamine → 6-fluoro-2-methyl-N-(5-methyl-3-phenylisoxazol-4-yl)-4-quinolinecarboxamide

HRID 1678311Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[CH:6]=[C:5]2[C:13](Cl)=[O:14].[NH2:16][C:17]1[C:18]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:19][O:20][C:21]=1[CH3:22]>N1C=CC=CC=1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[CH:6]=[C:5]2[C:13]([NH:16][C:17]1[C:18]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[N:19][O:20][C:21]=1[CH3:22])=[O:14]

Participants

Conditions

Temperature: 70 °C

Procedure

6-Fluoro-2-methylquinoline-4-carbonyl chloride (100 mg) and 4-amino-5-methyl-3-phenylisoxazole (200 mg) were dissolved in dichlorormethane (10 mL) and pyridine (0.3 mL). The reaction solution was heated at 70° C. overnight and then diluted with ethyl acetate (60 mL). The organic solution was washed with water (60 mL), dried, evaporated and purified by flash column chromatography (EtOAc/hexanes=1/1) to give 6-fluoro-2-methyl-N-(5-methyl-3-phenylisoxazol-4-yl)-4-quinolinecarboxamide (100 mg) as a white solid. 1H NMR (CDCl3): δ 2.58 (s, 3H), 2.76 (s, 3H), 7.14 (s, 1H), 7.44 (s, 1H), 7.49 (m, 4H), 7.67 (m, 2H), 7.82 (dd, J=2.7 and 9.9 Hz, 1H), 8.07 (dd, J=5.7 and 9.3 Hz, 1H); 19F NMR (282 MHz, CDCl3): δ-111.63; LCMS: ret. time: 21.32 min.; purity: 99.44%; MS (m/e): 362.06 (MH+).

Workup

washThe organic solution was washed with water (60 mL)
customdried
customevaporated
custompurified by flash column chromatography (EtOAc/hexanes=1/1)

Sources & evidence

ORD record: ord-a31267a978a14f9eaeccbd1e72b503e8
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08008501B2

Reaction notes

Loading…