Hydrochloric Acid → 2-(3-Dimethylaminomethyl-phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one

HRID 33292Notes

Reaction equation

HRID 33292 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([C:9]2[NH:10][C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:21](=[O:22])[NH:20][CH2:19][CH2:18][C:17]=2[C:16]=34)[CH:6]=[CH:7][CH:8]=1)=O.[CH3:23][NH:24][CH3:25].C([BH3-])#N.[Na+].Cl>CO.[Cl-].[Zn+2].[Cl-]>[CH3:23][N:24]([CH2:1][C:3]1[CH:4]=[C:5]([C:9]2[NH:10][C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:21](=[O:22])[NH:20][CH2:19][CH2:18][C:17]=2[C:16]=34)[CH:6]=[CH:7][CH:8]=1)[CH3:25]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 5003444Sodium cyanoborohydrideHCID 111090372-(3-formylphenyl)-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one

Product 1

HCID 98618522-(3-Dimethylaminomethyl-phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Procedure

The aldehyde compound 15 (346 mg, 1.19 mmol) in MeOH (40 mL) was treated with dimethyl amine (2M solution in MeOH, 7.16 mmol). The solution was cooled with an ice/water bath and treated dropwise with a solution of sodium cyanoborohydride (82 mg, 1.31 mmol) and zinc chloride (89 mg, 0.66 mmol) in MeOH (10 mL). The resulting solution was adjusted to pH=6-7 with 2M methanolic HCl. After stirring for 30 min., the reaction was quenched with conc. HCl (0.2 mL) and the methanol was removed by evaporation. The residue was diluted with water (30 mL). The solution was adjusted to pH=10-11 with KOH (s) and extracted with CH2Cl2 (30 mL×3). The organic solution was washed with water and brine, dried (Na2SO4), filtered, and concentrated. The crude product was crystallized (CH2Cl2/MeOH/hexanes) to give 2-(3-(N,N-dimethylamino)methylphenyl)-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one, 332 mg (87%), as shiny yellow crystals. mp 222-225° C.; 1H NMR (300 MHz, d6-DMSO) δ 2.20 (s, 6H), 3.06 (m, 2H), 3.40 (m, 2H), 3.50 (s, 2H), 7.21 (t, 1H, J=7.7 Hz), 7.41 (br d, 1H, J=7.4 Hz), 7.50 (m, 4H), 7.69 (d, 1H, J=7.1 Hz), 8.05 (br t, 1H), 11.56 (br s, 1H); HRMS (FAB, MH+) Calcd for C20H22N3O: 320.1763, Found: for C20H22N3O: 320.1763, Found: 320.1753; Anal. (C20H21N3O.0.25 H2O) C, H, N.

Workup

  1. temperatureThe solution was cooled with an ice/water bath
  2. customthe reaction was quenched with conc. HCl (0.2 mL)
  3. customthe methanol was removed by evaporation
  4. additionThe residue was diluted with water (30 mL)
  5. extractionextracted with CH2Cl2 (30 mL×3)
  6. washThe organic solution was washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was crystallized (CH2Cl2/MeOH/hexanes)

Sources & evidence

ORD record
ord-d12e4ec3c2f641ddaf9243b4e85851fa
Source dataset
uspto-grants-2008_09
Patent number
US07429578B2

Reaction notes

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