Methyl iodide → 3-(4-Fluorobenzoyl)-7-methoxy-1,2,3,6-tetrahydroazepino[4,5-B]indole-5-carboxylic acid ethyl ester

HRID 37954Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[C:15]([OH:20])=[CH:16][CH:17]=[CH:18][C:19]=3[C:11]=2[CH2:10][CH2:9][N:8]([C:21](=[O:29])[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH:7]=1)=[O:5])[CH3:2].[C:30](=O)([O-])[O-].[K+].[K+].CI>CC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[C:15]([O:20][CH3:30])=[CH:16][CH:17]=[CH:18][C:19]=3[C:11]=2[CH2:10][CH2:9][N:8]([C:21](=[O:29])[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH:7]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 3-(4-fluorobenzoyl)-7-hydroxy-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester (65 mg, 0.16 mmol), potassium carbonate (54 mg, 0.39 mmol), methyl iodide (0.4 mL, 6.4 mmol) and dry acetone (5 mL) was stirred at 60° C. for 13 hours. The potassium carbonate solid was filtered off, and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with hexane-EtOAc (90:10) to give the title compound as a yellow solid (36 mg, 55%); 1H-NMR (CDCl3): δ 10.56 (1H, s), 7.98 (1H, s), 7.64-7.59 (2H, m), 7.18-7.12 (3H, m), 7.03 (1H, t), 6.64 (1H, d), 4.28-4.19 (4H, m), 3.96 (3H, s), 3.26-3.24 (2H, m), 1.24 (3H, t); MS (ES): 409 (MH+).

Workup

filtrationThe potassium carbonate solid was filtered off
concentrationthe filtrate was concentrated in vacuo
customThe residue was purified by chromatography on silica gel eluting with hexane-EtOAc (90:10)

Sources & evidence

ORD record: ord-6c7b53a2e32944d2b907df281d164a85
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524704B2

Reaction notes

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