Acetic Acid → HCID 23283210, compound

HRID 370006Notes

Reaction equation

HRID 370006 reaction equation
[N:1]1[N:2]=[CH:3][N:4]([C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[NH:11][CH:10]=[C:9]3[CH2:15][CH2:16][NH2:17])[CH:5]=1.[CH2:18]([N:25]1[CH2:30][CH2:29][C:28](=[O:31])[CH2:27][CH2:26]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[C:32]([OH:35])(=[O:34])[CH3:33].C([BH3-])#N.[Na+].[OH-:40].[Na+]>CO>[C:32]([OH:35])(=[O:34])[C:33]([OH:31])=[O:40].[CH2:18]([N:25]1[CH2:30][CH2:29][CH:28]([NH:17][CH2:16][CH2:15][C:9]2[C:8]3[C:12](=[CH:13][CH:14]=[C:6]([N:4]4[CH:3]=[N:2][N:1]=[CH:5]4)[CH:7]=3)[NH:11][CH:10]=2)[CH2:27][CH2:26]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 192201-Benzyl-4-piperidoneHCID 5003444Sodium cyanoborohydrideHCID 23283176HCID 23283176, compound

Product 1

HCID 23283210HCID 23283210, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The organic layer was separated and the solvent evaporated. The crude product was purified by column chromatography on silica using dichloromethane/methanol/ammonia (40:8:1) to give 2-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]ethylamine as a brown oil (1.9 g, 49%). This tryptamine (1.0 g, 4.4 mmol), 1-benzylpiperidin-4-one (874 mg, 4.6 mmol), glacial acetic acid (1.58 g, 26.4 mmol) and sodium cyanoborohydride (290 mg, 4.6 mmol) were stirred in methanol (75 ml) at room temperature for 18 hours. The mixture was treated with 2M sodium hydroxide (to pH=8), evaporated and the aqueous partitioned between 2M sodium hydroxide (30 ml) and ethyl acetate (50 ml). The organic layer was separated and the aqueous re-extracted with ethyl acetate (2×50 ml). The combined organics were washed with saturated sodium chloride solution (2×30 ml), dried (sodium sulphate) and evaporated. The crude product was purified by column chromatography on silica using dichloromethane/methanol/ammonia (10:1:0.1) to afford the title compound free base as a solid (1.4 g, 79%). The hydrogen oxalate salt had mp 187-189° C., MS, ES+, m/z=401 for (M+H)+. (Found: C, 56.11; H, 5.88; N, 14.08. C24H28N6. 2C2H2O4. H2O requires C, 56.18; H, 5.72; N, 14.04%).

Workup

  1. customevaporated
  2. customthe aqueous partitioned between 2M sodium hydroxide (30 ml) and ethyl acetate (50 ml)
  3. customThe organic layer was separated
  4. extractionthe aqueous re-extracted with ethyl acetate (2×50 ml)
  5. washThe combined organics were washed with saturated sodium chloride solution (2×30 ml)
  6. dry with materialdried (sodium sulphate)
  7. customevaporated
  8. customThe crude product was purified by column chromatography on silica

Sources & evidence

ORD record
ord-cbd59d59ab0c4d239892ca6b405fec62
Source dataset
uspto-grants-2000_10
Patent number
US06140347

Reaction notes

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