Dimethylcarbamoyl Chloride → 8-Dimethylcarbamoyloxy-3-(4-fluorobenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-B]indole-5-carboxylic acid ethyl ester

HRID 736089

Reaction equation

[CH3:1][N:2]([CH3:6])[C:3](Cl)=[O:4].[CH2:7]([O:9][C:10]([C:12]1[C:18]2[NH:19][C:20]3[CH:21]=[C:22]([OH:26])[CH:23]=[CH:24][C:25]=3[C:17]=2[C:16]([CH3:28])([CH3:27])[CH2:15][N:14]([C:29](=[O:37])[C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[CH:13]=1)=[O:11])[CH3:8].C(N(CC)CC)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH2:7]([O:9][C:10]([C:12]1[C:18]2[NH:19][C:20]3[CH:21]=[C:22]([O:26][C:3](=[O:4])[N:2]([CH3:6])[CH3:1])[CH:23]=[CH:24][C:25]=3[C:17]=2[C:16]([CH3:28])([CH3:27])[CH2:15][N:14]([C:29](=[O:37])[C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[CH:13]=1)=[O:11])[CH3:8]

Participants

Conditions

Temperature: 50 °C

Procedure

Dimethylcarbamoyl chloride (0.2 mL, 2.17 mmol) was added dropwise to a stirred solution of 3-(4-fluorobenzoyl)-8-hydroxy-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester (199 mg, 0.47 mmol), 4-dimethylaminopyridine (DMAP) (20 mg), and triethylamine (0.8 mL, 5.74 mmol) in anhydrous DCM (15 mL) at 0° C. under nitrogen, and the resulting mixture was stirred at 50° C. for 5 hours. The solvents were removed in vacuo, and the residue was purified by chromatography on silica gel eluting with DCM-20% MeOH/DCM (90:10) to give the title compound (171 mg, 74%); 1H-NMR (CDCl3): δ 10.62 (1H, s), 7.78 (s, 1H), 7.74 (1H, d), 7.63-7.59 (2H, m), 7.16-7.10 (3H, m), 6.84 (1H, dd), 4.24 (2H, q), 4.08 (2H, brs), 3.14 (3H, s), 3.03 (3H, s), 1.59 (6H, s), 1.23 (3H, t); MS (ES): 494 (MH+).

Workup

customThe solvents were removed in vacuo
customthe residue was purified by chromatography on silica gel eluting with DCM-20% MeOH/DCM (90:10)

Sources & evidence

ORD record: ord-f798b4c81ad24bc79445b73271f00257
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07595311B2

Linked notes

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