Dimethylamine, hydrochloride → 5-Chloro-1H-indole-2-carboxylic acid [1-benzyl-2-(4-methylamino-piperidin-1-yl)-2-oxo-ethyl]-amide

HRID 1872109Notes

Reaction equation

HRID 1872109 reaction equation
Cl.[CH3:2][NH:3]C.C([O-])(=O)C.[Na+].C([BH3-])#N.[Na+].[CH2:14]([CH:21]([NH:31][C:32]([C:34]1[NH:35][C:36]2[C:41]([CH:42]=1)=[CH:40][C:39]([Cl:43])=[CH:38][CH:37]=2)=[O:33])[C:22](=[O:30])[N:23]1[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CO>[CH2:14]([CH:21]([NH:31][C:32]([C:34]1[NH:35][C:36]2[C:41]([CH:42]=1)=[CH:40][C:39]([Cl:43])=[CH:38][CH:37]=2)=[O:33])[C:22]([N:23]1[CH2:28][CH2:27][CH:26]([NH:3][CH3:2])[CH2:25][CH2:24]1)=[O:30])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 10473Dimethylamine, hydrochlorideHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 543267115-chloro-1H-indole-2-carboxylic acid [1-benzyl-2-oxo-2-(4-oxo-piperidin-1-yl)-ethyl]-amide

Product 1

HCID 536941855-Chloro-1H-indole-2-carboxylic acid [1-benzyl-2-(4-methylamino-piperidin-1-yl)-2-oxo-ethyl]-amideYield 82%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Dimethylamine hydrochloride (1.1 mmol), sodium acetate (2.1 mmol), activated 3Å molecular seives, and sodium cyanoborohydride (0.25 mmol) were added in this order to 5-chloro-1H-indole-2-carboxylic acid [1-benzyl-2-oxo-2-(4-oxo-piperidin-1-yl)-ethyl]-amide (0.21 mmol) in methanol (2 mL) at 0° C. After 18 hours, the mixture was concentrated, the residue taken up in ethyl acetate, the resulting solution washed with 2N NaOH and brine, dried with Na2SO4 and concentrated. The product was purified by chromatography on silica gel eluted with 1-8% ethanol in dichloromethane containing 0.5% NH4OH followed by trituration with ether: Yield 82%; HPLC (60/40) 2.79 minutes (98%); PBMS 439/441 (MH+,100%);

Workup

  1. concentrationthe mixture was concentrated
  2. washthe resulting solution washed with 2N NaOH and brine
  3. dry with materialdried with Na2SO4
  4. concentrationconcentrated
  5. customThe product was purified by chromatography on silica gel
  6. washeluted with 1-8% ethanol in dichloromethane containing 0.5% NH4OH
  7. customHPLC (60/40) 2.79 minutes (98%)

Sources & evidence

ORD record
ord-628526e9e134479287792ccc7b56de55
Source dataset
uspto-grants-2000_08
Patent number
US06107329

Reaction notes

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