5-(4-chlorophenyl)-2-methoxy-10-methyl-7H-isoxazolo[5,4-c]pyrido[2,3-e]azepine → 5-(4-Chlorophenyl)-10-methyl-1H-isoxazolo[5,4-c]pyrido[2,3-e]azepin-2(7H)-one

HRID 2401408Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[CH:22]=[CH:21][C:20]([O:23]C)=[N:19][C:10]=3[C:11]3[C:17]([CH3:18])=[N:16][O:15][C:12]=3[CH2:13][N:14]=2)=[CH:4][CH:3]=1>CC(O)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[CH:22]=[CH:21][C:20](=[O:23])[NH:19][C:10]=3[C:11]3[C:17]([CH3:18])=[N:16][O:15][C:12]=3[CH2:13][N:14]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 5-(4-chlorophenyl)-2-methoxy-10-methyl-7H-isoxazolo[5,4-c]pyrido[2,3-e]azepine (0.050 g, 0.147 mmol) in AcOH (1 mL) was added concentrated 48% hydrobromic acid (1 mL) at room temperature. The reaction was heated to 100° C. for 2 h before it was diluted with water, and the desired product was extracted with a mixture CH2Cl2/trifluoroethanol (19:1) (repeated 4 times). The organic layers were combined, dried over Na2SO4 and concentrated to dryness. The residue was purified by flash chromatography (hexane/EtOAc 7:3 to 0:10) to give the title compound as a white solid (0.019 g). LC/MS m/z 326 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 11.79 (br. s, 1H), 7.51-7.41 (m, 4H), 7.36 (br. s, 1H), 6.41 (br. s, 1H), 4.53 (br. s, 2H), 2.55 (s, 3H).

Workup

concentrationconcentrated 48% hydrobromic acid (1 mL) at room temperature
additionwas diluted with water
extractionthe desired product was extracted with a mixture CH2Cl2/trifluoroethanol (19:1) (repeated 4 times)
dry with materialdried over Na2SO4
concentrationconcentrated to dryness
customThe residue was purified by flash chromatography (hexane/EtOAc 7:3 to 0:10)

Sources & evidence

ORD record: ord-7bcf750f3a0f4d3abfa747111bdf8093
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796261B2

Reaction notes

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