Tris(hydroxymethyl)aminomethane → Ethyl 3-(4-fluorobenzoyl)-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate

HRID 1258044Notes

Reaction equation

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

Participants

Conditions

Temperature: 20 °C

Procedure

To a solution of ethyl 1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate (Example 4, 52 mg, 0.2 mmol) in DCM was added 4-fluorobenzoyl chloride (36 μL, 0.2 mmol) and TEA (56 μL, 0.4 mmol) and the mixture was shaken overnight at 20° C. Trisamine resin (50 mg) was added and the suspension was shaken for 2 hours at 20° C. The resin was removed by filtration through a Florisil® cartridge. Evaporation of solvent gave a crude product, which was purified by trituration with methanol to give the title compound (28 mg); 1H-NMR (CDCl3): δ 10.31 (1 H, br s), 7.79 (1 H, s), 7.41 (2H, m), 7.36 (1H, d), 6.90-7.04 (5H, m), 3.99-4.06 (4H, m), 3.06 (2H, t), 1.02 (3H, t); MS (ES): 379 (MH+).

Workup

stirringthe suspension was shaken for 2 hours at 20° C
customThe resin was removed by filtration through a Florisil® cartridge
customEvaporation of solvent
customgave a crude product, which
customwas purified by trituration with methanol

Sources & evidence

ORD record: ord-211e9f7f57a144e695e2cbe12e9fb5f0
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08466143B2

Reaction notes

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