Potassium Carbonate → 2-(4-oxiranylmethyl-[1,4]diazepan-1-yl)-1-phenyl-1H-indole-3-carboxaldehyde

HRID 1678148Notes

Reaction equation

HRID 1678148 reaction equation
[N:1]1([C:8]2[N:9]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:10]3[C:15]([C:16]=2[CH:17]=[O:18])=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH2:25]([CH:27]1[O:29][CH2:28]1)Br.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[O:29]1[CH2:28][CH:27]1[CH2:25][N:4]1[CH2:5][CH2:6][CH2:7][N:1]([C:8]2[N:9]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:10]3[C:15]([C:16]=2[CH:17]=[O:18])=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 18430EpibromohydrinHCID 597547512-[1,4]diazepan-1-yl-1-phenyl-1H-indole-3-carboxaldehyde

Product 1

HCID 114743112-(4-oxiranylmethyl-[1,4]diazepan-1-yl)-1-phenyl-1H-indole-3-carboxaldehydeYield 41%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 2-[1,4]diazepan-1-yl-1-phenyl-1H-indole-3-carboxaldehyde (438 mg, 1.37 mmol), epibromohydrin (188 mg, 1.37 mmol) and potassium carbonate (758 mg, 5.49 mmol) in acetonitrile (20 mL) is refluxed for 2.5 hr. The reaction mixture is cooled, the solvent is removed and the residue is purified by chromatography eluting with dichloromethane-1 to 5% methanol. Fractions containing product are combined and concentrated to afford 2-(4-oxiranylmethyl-[1,4]diazepan-1-yl)-1-phenyl-1H-indole-3-carboxaldehyde (41% yield) as a yellow solid. LC/MS: 376 (M+H), RT 2.65 min; NMR (CDCl3): 10.28 (1H, s), 8.26 (1H, d), 7.43-7.65 (3H, m), 7.17-7.42 (3H, m), 7.13(1H, t), 6.96 (1H, d), 3.49 (4H, m), 3.03 (1H, m), 2.56-2.86 (4H, m), 2.30-2.50 (2H, m), 1.74(2H, m), 1.56 (2H, s).

Workup

  1. temperatureThe reaction mixture is cooled
  2. customthe solvent is removed
  3. customthe residue is purified by chromatography
  4. washeluting with dichloromethane-1 to 5% methanol
  5. additionFractions containing product
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f2c510f9c28a48d08b3fb5e2de2b2a8b
Source dataset
uspto-grants-2011_08
Patent number
US08008491B2

Reaction notes

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