Sodium hydride → 6-(5-Cyano-2-hydroxy-1H-indol-3-yl)-N-methyl-N-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide hydrochloride

HRID 748549Notes

Reaction equation

HRID 748549 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6]2)#[N:2].[H-].[Na+].[Cl:15][C:16]1[N:21]=[CH:20][C:19]([S:22]([N:25]([CH3:33])[CH2:26][CH2:27][N:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1.C([O-])(O)=O.[Na+]>CN(C)C=O>[ClH:15].[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([OH:12])=[C:6]2[C:16]1[N:21]=[CH:20][C:19]([S:22]([N:25]([CH3:33])[CH2:26][CH2:27][N:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1)#[N:2]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 27733462-Oxo-2,3-dihydro-1H-indole-5-carbonitrileHCID 632074446-Chloro-N-methyl-N-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide

Product 1

HCID 1363421366-(5-Cyano-2-hydroxy-1H-indol-3-yl)-N-methyl-N-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide hydrochlorideYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To an ice-cooled solution of 5-cyanooxindole (200 mg, 1.26 mmol) in N,N-dimethylformamide (5 mL) was added sodium hydride (60 mg, 1.5 mmol). The reaction mixture was stirred for 25 min whereafter 6-chloro-N-methyl-N-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide (303 mg, 1 mmol) was added. The reaction mixture was heated at 130° C. for 1 h and then allowed to cool to room temperature. An aqueous saturated solution of NaHCO3 (50 mL) was added and the water phase was extracted with ethyl acetate. The organic phase was dried (Na2SO4) and purified on a silica gel column using chloroform/methanol/conc NH3(aq), (500:35:3.5 to 500:50:5), as the eluent. The solvents were evaporated in vacuo and the residue was stirred over night in ethyl acetate, filtered and dried to give 160 mg (38% yield) of the title compound as the base. The base, dissolved in chloroform/methanol, was treated with HCl in diethyl ether to give the title compound: MS (ES) m/z 426 (M++1).

Workup

  1. additionwas added
  2. temperatureto cool to room temperature
  3. extractionthe water phase was extracted with ethyl acetate
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. custompurified on a silica gel column
  6. customThe solvents were evaporated in vacuo
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-68cffc6875a44cc58382d2f43f45c8ff
Source dataset
uspto-grants-2008_07
Patent number
US07399780B2

Reaction notes

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