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

HRID 474914Notes

Reaction equation

HRID 474914 reaction equation
Cl.[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][N:13]([C:16]2[CH:17]=[CH:18][C:19]3[C:20]4[CH2:30][NH:29][CH2:28][CH2:27][CH2:26][C:21]=4[N:22]([CH3:25])[C:23]=3[CH:24]=2)[C:12](=[O:31])[CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C=O.[C:34](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>CO.C(Cl)Cl>[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][N:13]([C:16]2[CH:17]=[CH:18][C:19]3[C:20]4[CH2:30][N:29]([CH3:34])[CH2:28][CH2:27][CH2:26][C:21]=4[N:22]([CH3:25])[C:23]=3[CH:24]=2)[C:12](=[O:31])[CH:11]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 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 498693484-(Benzyloxy)-1-(2,6-dimethyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-oneYield 48.4%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

4-(Benzyloxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-one hydrochloride (54 mg, 0.12 mmol) and 37% aqueous formaldehyde (15 μL, 0.17 mmol) were dissolved in 1:1 MeOH/CH2Cl2 (1.0 mL), and the resulting solution was stirred at room temperature for 5 min. Sodium triacetoxyborohydride (52 mg, 0.25 mmol) was added, and the reaction stirred at room temperature for an additional 45 min. The mixture was neutralized with saturated NaHCO3 solution and extracted with CH2Cl2 (2×10 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 (24 mg, 46%) as a yellow film: 1H NMR (300 MHz, CD3OD) δ 7.60-7.55 (m, 2H), 7.47-7.35 (m, 6H), 7.01-6.98 (m, 1H), 6.29-6.26 (m, 1H), 6.11 (d, J=2.7 Hz, 1H), 5.48 (s, 2H), 5.17 (s, 2H), 4.16-4.10 (m, 2H), 3.74-3.73 (m, 3H), 3.10-3.06 (m, 2H), 2.61 (s, 3H), 2.12-2.06 (m, 2H).

Workup

  1. stirringthe reaction stirred at room temperature for an additional 45 min
  2. extractionextracted with CH2Cl2 (2×10 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-437f3269a1c149e69182d37712875079
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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