Acetaldehyde → 4-(Benzyloxy)-1-(2-ethyl-6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-one

HRID 474916Notes

Reaction equation

HRID 474916 reaction equation
[CH:1](=O)[CH3:2].Cl.[CH2:5]([O:12][C:13]1[CH:18]=[CH:17][N:16]([C:19]2[CH:20]=[CH:21][C:22]3[C:23]4[CH2:33][NH:32][CH2:31][CH2:30][CH2:29][C:24]=4[N:25]([CH3:28])[C:26]=3[CH:27]=2)[C:15](=[O:34])[CH:14]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CC(O)=O>[CH2:5]([O:12][C:13]1[CH:18]=[CH:17][N:16]([C:19]2[CH:20]=[CH:21][C:22]3[C:23]4[CH2:33][N:32]([CH2:1][CH3:2])[CH2:31][CH2:30][CH2:29][C:24]=4[N:25]([CH3:28])[C:26]=3[CH:27]=2)[C:15](=[O:34])[CH:14]=1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 177Acetaldehyde2×HCID 516892Sodium BicarbonateHCID 498686694-(Benzyloxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-one hydrochloride

Product 1

HCID 498693494-(Benzyloxy)-1-(2-ethyl-6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-oneYield 54%

Reagents, catalysts & solvents 1

HCID 21922555Acetic acid methylene chlorideSolvent

Procedure

Acetaldehyde (50 μL, 0.88 mmol) and picoline borane complex (47 mg, 0.43 mmol) were added to a suspension of 4-(benzyloxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-one hydrochloride (64 mg, 0.18 mmol) in 10:1 CH2Cl2/AcOH (5.0 mL), and the resulting solution was stirred at ambient temperature for 2 h. Additional acetaldehyde (50 μL, 0.88 mmol) was added to the solution, and the resulting mixture was stirred for 18 h. The mixture was neutralized with saturated NaHCO3 solution and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to dryness. Flash chromatography (12 g ISCO CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 2 column volumes to 0:100 over 20 column volumes) provided the title compound (34 mg, 54%) as a yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 7.56 (d, J=7.5 Hz, 1H), 7.48-7.41 (m, 5H), 7.39-7.37 (m, 1H), 7.35 (d, J=2.0 Hz, 1H), 6.87 (dd, J=8.5, 2.0 Hz, 1H), 6.07 (dd, J=7.5, 3.0 Hz, 1H), 5.96 (d, J=3.0 Hz, 1H), 5.14 (s, 2H), 3.88 (s, 2H), 3.66 (s, 3H), 3.03-3.01 (m, 2H), 2.94 (t, J=5.5 Hz, 2H), 2.46-2.42 (m, 2H), 1.78-1.76 (m, 2H), 1.01 (t, J=7.0 Hz, 3H); ESI MS m/z 428 [M+H]+.

Workup

  1. stirringthe resulting mixture was stirred for 18 h
  2. extractionextracted with CH2Cl2 (3×20 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-a4ad0dbf80d84b3ab1cc7d85acdafe74
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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