Acetyl chloride → HCID 49870327, compound

HRID 474957Notes

Reaction equation

HRID 474957 reaction equation
C(N(CC)CC)C.[C:8](Cl)(=[O:10])[CH3:9].Cl.[F:13][C:14]1[CH:15]=[CH:16][C:17]([CH2:20][O:21][C:22]2[CH:27]=[CH:26][N:25]([C:28]3[CH:29]=[CH:30][C:31]4[C:32]5[CH2:42][NH:41][CH2:40][CH2:39][CH2:38][C:33]=5[N:34]([CH3:37])[C:35]=4[CH:36]=3)[C:24](=[O:43])[CH:23]=2)=[N:18][CH:19]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:8]([N:41]1[CH2:40][CH2:39][CH2:38][C:33]2[N:34]([CH3:37])[C:35]3[CH:36]=[C:28]([N:25]4[CH:26]=[CH:27][C:22]([O:21][CH2:20][C:17]5[CH:16]=[CH:15][C:14]([F:13])=[CH:19][N:18]=5)=[CH:23][C:24]4=[O:43])[CH:29]=[CH:30][C:31]=3[C:32]=2[CH2:42]1)(=[O:10])[CH3:9]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 66874825HCID 66874825, compound

Product 1

HCID 49870327HCID 49870327, compoundYield 70.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (48 μL, 0.34 mmol), DMAP (4.0 mg, 0.034 mmol) and acetyl chloride (18 μL, 0.26 mmol) were added to a solution of 4-((5-fluoropyridin-2-yl)methoxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-one hydrochloride (78 mg, 0.17 mmol) in CH2Cl2 (10 mL), and the resulting solution was stirred at ambient temperature for 3 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 (55 mg, 70%) as an off-white solid: mp 78-83° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.62 (d, J=3.0 Hz, 1H), 7.83 (ddd, J=8.5, 8.5, 3.0 Hz, 1H), 7.66-7.49 (m, 3H), 7.39 (dd, J=21.0, 2.0 Hz, 1H), 6.93 (ddd, J=22.5, 8.0, 1.5 Hz, 1H), 6.11 (dd, J=7.5, 2.5 Hz, 1H), 5.96 (dd, J=5.0, 3.0 Hz, 1H), 5.21 (s, 2H), 4.69-4.68 (m, 2H), 3.78-3.75 (m, 2H), 3.67-3.65 (m, 3H), 3.03-2.96 (m, 2H), 2.09-1.90 (m, 5H); ESI MS m/z 461 [M+H]+; HPLC (Method A) 98.7% (AUC), tR=16.0 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-1275eb1049944e6496acc262289d09f5
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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