Sodium hydride → HCID 136342118, compound

HRID 748536Notes

Reaction equation

HRID 748536 reaction equation
[H-].[Na+].[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)#[N:4].[Cl:15][C:16]1[CH:30]=[CH:29][C:19]([C:20]([N:22]([CH2:24][CH2:25][N:26]([CH3:28])[CH3:27])[CH3:23])=[O:21])=[CH:18][N:17]=1>CN(C)C=O>[ClH:15].[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([OH:14])=[C:8]2[C:16]1[CH:30]=[CH:29][C:19]([C:20]([N:22]([CH2:24][CH2:25][N:26]([CH3:27])[CH3:28])[CH3:23])=[O:21])=[CH:18][N:17]=1)#[N:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27733462-Oxo-2,3-dihydro-1H-indole-5-carbonitrileHCID 63694331HCID 63694331, compound

Product 1

HCID 136342118HCID 136342118, compoundYield 4.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A mixture of sodium hydride (330 mg, 8.2 mmol, 60% dispersion in oil, pre-washed with hexane) in N,N-dimethylformamide (2 mL) was added to 5-cyanooxindole (980 mg, 6.2 mmol) in N,N-dimethylformamide (4 mL). The formed brown mixture was stirred at room temperature for 20 min and 6-chloro-N-[2-(dimethylamino)ethyl]-N-methylnicotinamide (500 mg, 2.1 mmol) in N,N-dimethylformamide (3 mL) was added. The obtained red solution was heated at 150° C. for 30 min and was then allowed to reach room temperature overnight. The solvent was removed in vacuo and the residue was partitioned between a 2 M aqueous HCl solution and ethyl acetate. The mixture was alkalized to pH 8 by adding NaHCO3 (s) and extracted with ethyl acetate. The combined extracts were dried (Na2SO4) and the solvent was removed in vacuo to afford 450 mg of a crude product. The residue was purified on a silica gel column using chloroform/methanol/conc. NH3(aq), (80:19:1), as the eluent. Fractions containing product were collected, evaporated in vacuo and dried at 25° C. in vacuo to afford 70 mg. The residue was purified by preparative HPLC (column: Xterra, 19×300 mm, eluent: 0.05 M NH4OAc buffert/acetonitrile, 9:1-3:7). Fractions containing product were collected, evaporated in vacuo and dried at 25° C. in vacuo to afford 35 mg (4.6% yield) of the title compound as the base: 1H NMR (D2O, 400 MHz) δ 7.89 (s, 1 H), 7.59 (d, J=9 Hz, 1 H), 6.96 (s, 1 H), 6.92 (d, J=8 Hz, 1 H), 6.84 (d, J=9 Hz, 1 H), 6.65 (d, J=8 Hz, 1 H), 3.76 (s, 2 H), 3.30 (s, 2 H), 3.07 (s, 3 H), 2.84 (s, 6 H).

Workup

  1. temperatureThe obtained red solution was heated at 150° C. for 30 min
  2. waitto reach room temperature overnight
  3. customThe solvent was removed in vacuo
  4. customthe residue was partitioned between a 2 M aqueous HCl solution and ethyl acetate
  5. additionby adding NaHCO3 (s)
  6. extractionextracted with ethyl acetate
  7. dry with materialThe combined extracts were dried (Na2SO4)
  8. customthe solvent was removed in vacuo
  9. customto afford 450 mg of a crude product
  10. customThe residue was purified on a silica gel column
  11. additionFractions containing product
  12. customwere collected
  13. customevaporated in vacuo
  14. customdried at 25° C. in vacuo
  15. customto afford 70 mg
  16. customThe residue was purified by preparative HPLC (column: Xterra, 19×300 mm, eluent: 0.05 M NH4OAc buffert/acetonitrile, 9:1-3:7)
  17. additionFractions containing product
  18. customwere collected
  19. customevaporated in vacuo
  20. customdried at 25° C. in vacuo

Sources & evidence

ORD record
ord-4663884771664138880b41130700da18
Source dataset
uspto-grants-2008_07
Patent number
US07399780B2

Reaction notes

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