Acetyl chloride → 1-(2-Acetyl-6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-2(1H)-one

HRID 474958Notes

Reaction equation

HRID 474958 reaction equation
C(N(CC)CC)C.[C:8](Cl)(=[O:10])[CH3:9].Cl.[CH3:13][N:14]1[C:22]2[CH:21]=[C:20]([N:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:30]=[N:31][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:33][CH:34]=4)=[CH:25][C:24]3=[O:39])[CH:19]=[CH:18][C:17]=2[C:16]2[CH2:40][NH:41][CH2:42][CH2:43][CH2:44][C:15]1=2>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:8]([N:41]1[CH2:42][CH2:43][CH2:44][C:15]2[N:14]([CH3:13])[C:22]3[CH:21]=[C:20]([N:23]4[CH:28]=[CH:27][C:26]([C:29]5[CH:30]=[N:31][C:32]([C:35]([F:36])([F:38])[F:37])=[CH:33][CH:34]=5)=[CH:25][C:24]4=[O:39])[CH:19]=[CH:18][C:17]=3[C:16]=2[CH2:40]1)(=[O:10])[CH3:9]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 668731281-(6-Methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-2(1H)-one hydrochloride

Product 1

HCID 498703281-(2-Acetyl-6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-2(1H)-oneYield 59%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (58 μL, 0.41 mmol), DMAP (5.0 mg, 0.041 mmol) and acetyl chloride (22 μL, 0.31 mmol) were added to a solution of 1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-2(1H)-one hydrochloride (97 mg, 0.21 mmol) in CH2Cl2 (15 mL), and the resulting solution was stirred at ambient temperature for 18 h under N2. The resulting solution was concentrated to dryness under reduced pressure. Flash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 2 column volumes, increased to 50:50 over 20 column volumes and held for 1 column volume, then increased to 0:100 over 10 column volumes and held for 12 column volumes) gave the title compound (58 mg, 59%) as a yellow powder: mp 156-162° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.19 (s, 1H), 8.49 (dd, J=8.0, 2.0 Hz, 1H), 8.05 (d, J=8.0 Hz, 1H), 7.88-7.83 (m, 1H), 7.72-7.49 (m, 2H), 7.07-6.99 (m, 2H), 6.80-6.78 (m, 1H), 4.72-4.70 (m, 2H), 3.79-3.76 (m, 2H), 3.69-3.68 (m, 3H), 3.05-2.98 (m, 2H), 2.02-1.90 (m, 5H); ESI MS m/z 481 [M+H]+; HPLC (Method A)>99% (AUC), tR=18.1 min.

Workup

  1. concentrationThe resulting solution was concentrated to dryness under reduced pressure
  2. temperatureFlash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 2 column volumes, increased to 50:50 over 20 column volumes
  3. temperatureincreased to 0:100 over 10 column volumes

Sources & evidence

ORD record
ord-12b4976423484b9c9ad0461ba8d38ecf
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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