Sodium hydride → HCID 18669084, compound

HRID 1058979Notes

Reaction equation

HRID 1058979 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:5]([Cl:37])=[CH:6][CH:7]=[C:8]([C:10]2[NH:11][C:12]3[C:17]([C:18]=2[CH2:19][CH2:20][C:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=4[O:35][CH3:36])[CH2:25][CH2:24]2)=[O:22])=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:9]=1.[CH3:38][S:39](Cl)(=[O:41])=[O:40].[Cl-].[NH4+]>CN(C)C=O>[Cl:3][C:4]1[C:5]([Cl:37])=[CH:6][CH:7]=[C:8]([C:10]2[N:11]([S:39]([CH3:38])(=[O:41])=[O:40])[C:12]3[C:17]([C:18]=2[CH2:19][CH2:20][C:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=4[O:35][CH3:36])[CH2:25][CH2:24]2)=[O:22])=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:9]=1

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chloride2×HCID 18669079HCID 18669079, compound

Product 1

HCID 18669084HCID 18669084, compoundYield 51.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil, 13 mg, 0.3 mmol) was added to a solution of 1-{3-[2-(5-chloro-4-chlorophenyl)-1H-indol-3-yl]-1-oxopropyl}-4-(2-methoxyphenyl)piperazine (Example 85, 52 mg, 0.1 mmol) in N,N-dimethylformamide (1 mn) and the mixture was stirred at room temperature for 5 min. Methanesulfonyl chloride (10 μl, 15 mg, 0.13 mmol) was added and the mixture was stirred at room temperature for 10 min. Further sodium hydride (60% dispersion in mineral oil, 50 mg, 1.2 mmol) and methanesulfonyl chloride (20 μl, 30 mg, 0.26 mmol) were added and the mixture was stirred at room temperature for 10 min. Saturated aqueous ammonium chloride (10 mL) was added and the mixture was extracted with ethyl acetate. The combined organic fractions were washed with aqueous ammonium chloride (10%, 10 mL) dried (Na2SO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/ether (50:50) to give the title compound as a colorless glass (30 mg, 51%). 1H NMR (360 MHz, CDCl3) δ8.04 (1H, d, J 8.8 Hz), 7.62 (1H, d, J 2.1 Hz), 7.45 (2H, d, J 8.5 Hz), 7.37 (2H, d, J 8.5 Hz), 7.36 (1H, dd, J 8.8, 2.1 Hz), 7.03 (1H, t, J 7.7 Hz), 6.94-6.85 (3H, m), 3.87 (3H, s), 3.75 (2H, m), 3.38 (2H, m), 2.98-2.86 (6H, m), 2.81 (3H, s), and 2.45 (2H, m). m/z (ES+) 586, 588 (M+1).

Workup

  1. stirringthe mixture was stirred at room temperature for 10 min
  2. stirringthe mixture was stirred at room temperature for 10 min
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe combined organic fractions were washed with aqueous ammonium chloride (10%, 10 mL)
  5. dry with materialdried (Na2SO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with hexane/ether (50:50)

Sources & evidence

ORD record
ord-4c92556224704a9cbdbc2d284ec4a951
Source dataset
uspto-grants-2003_02
Patent number
US06518273B1

Reaction notes

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