Water → HCID 18669083, compound

HRID 1058975Notes

Reaction equation

HRID 1058975 reaction equation
[H-].[Na+].[O:3]=[C:4]1[NH:9][CH2:8][CH2:7][N:6]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:5]1.[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([CH3:30])[C:25]([C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)=[CH:24]2.[CH3:38][CH2:39][C:40](Cl)=[O:41].O>CN(C=O)C>[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([CH3:30])[C:25]([C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)=[C:24]2[CH2:38][CH2:39][C:40]([N:9]1[CH2:8][CH2:7][N:6]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:5][C:4]1=[O:3])=[O:41]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 736777Benzyl 3-oxopiperazine-1-carboxylateHCID 86758835HCID 86758835, compound

Product 1

HCID 18669083HCID 18669083, compoundYield 5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Oxalyl chloride (0.08 mL, 114 mg, 0.9 mmol) was added dropwise to a stirred, cooled (0° C.) solution of 5-chloro-2-(4-chlorophenyl)-1-methyl-1H-indole-3-propanoic acid (Description 12, 330 mg, 0.95 mmol) and DMF (1 drop) in toluene (15 mL) and the mixture was stirred at room temperature for 2 h. to give a solution of 5-chloro-2-(4-chlorophenyl)-1-methyl-1H-indole-3-propanoyl chloride. Sodium hydride (60% dispersion in mineral oil, 19 mg, 0.48 mmol) was added to a solution of phenylmethyl 3-oxo-1-piperazinecarboxylate (Eur.J.Med.Chem. 1981, 16, 229-232) (111 mg, 0.48 mmol) in DMF (3 mL) and the mixture was stirred at room temperature for 30 min. A portion of the solution of 5-chloro-2-(4-chlorophenyl)-1-methyl-1H-indole-3-propanoyl chloride (7.5 mL) was added dropwise and the mixture was stirred at room temperature overnight. Water was added and the mixture was extracted with ether. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/EtOAc (80:20). The fractions containing product were combined, washed with aqueous sodium hydroxide (4M) and water, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane and washed with aqueous hydrochloric acid (2M), saturated aqueous sodium carbonate and water, dried (MgSO4) and the solvent was evaporated under reduced pressure to give the title compound as a colorless oil (14 mg, 5%). δ7.58 (1H, s), 7.47 (2H, d, J 8.4 Hz), 7.39-7.16 (9H, m), 5.15 (2H, s), 4.22 (2H, s), 3.81 (2H, m), 3.61 (2H, m), 3.53 (3H, s), 3.15 (2H, m), and 3.00 (2H, m). m/z (ES+) 564, 566 (M+1).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractionthe mixture was extracted with ether
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by flash column chromatography on silica gel
  6. washeluting with hexane/EtOAc (80:20)
  7. additionThe fractions containing product
  8. washwashed with aqueous sodium hydroxide (4M) and water
  9. dry with materialdried (MgSO4)
  10. customthe solvent was evaporated under reduced pressure
  11. dissolutionThe residue was dissolved in dichloromethane
  12. washwashed with aqueous hydrochloric acid (2M), saturated aqueous sodium carbonate and water
  13. dry with materialdried (MgSO4)
  14. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-9e91c8f2b5a146b5bf18fd2974d5d07d
Source dataset
uspto-grants-2003_02
Patent number
US06518273B1

Reaction notes

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