Sodium hydride → HCID 136342117, compound

HRID 748535Notes

Reaction equation

HRID 748535 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[C:16]1[N:21]=[CH:20][N:19]=[C:18]([O:22][CH2:23][CH2:24][N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[CH:17]=1>CN(C)C=O>[OH:12][C:7]1[NH:8][C:9]2[C:5]([C:6]=1[C:16]1[CH:17]=[C:18]([O:22][CH2:23][CH2:24][N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[N:19]=[CH:20][N:21]=1)=[CH:4][C:3]([C:1]#[N:2])=[CH:11][CH:10]=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27733462-Oxo-2,3-dihydro-1H-indole-5-carbonitrileHCID 85873129HCID 85873129, compound

Product 1

HCID 136342117HCID 136342117, compoundYield 31.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 5-cyanooxindole (411 mg, 2.60 mmol) in N,N-dimethylformamide (4 mL) was added sodium hydride (181 mg, 4.52 mmol, 60% dispersion in oil). After 10 min, a solution of 4-(2-[(6-chloropyrimidin-4-yl)oxy]ethyl )morpholine (367 mg, 1.51 mmol) in N,N-dimethylformamide (1.5 mL) was added dropwise. The mixture was stirred at room temperature for 3 h. The solvent was removed in vacuo, and the residue was suspended in a 2 M aqueous HCl solution and washed twice with ethyl acetate. The aqueous layer was alkalized to pH 8 by adding a 45% aqueous NaOH solution. The obtained suspension was extracted twice with ethyl acetate. The combined phases were washed with brine, dried (Na2SO4) and the solvent was removed in vacuo. The crude product was purified on a silica gel column using chloroform/ethanol, (9:1), to chloroform/methanol, (8:2), as the eluent affording 172 mg (31% yield) of the title compound as a yellow solid: 1H NMR (DMSO-d6, 400 MHz) δ 10.89 (br s, 1 H), 8.62 (s, 1 H), 8.02 (s, 1 H), 7.30 (d, J=7 Hz, 1 H), 6.97 (d, J=8 Hz, 1 H), 6.83 (br s, 1 H), 4.52 (t, J=5 Hz, 2 H), 3.60 (t, J=4 Hz, 4 H), 2.77 (m, 2 H), 2.54 (m, 4 H); MS (TSP) m/z 366 (M++1).

Workup

  1. customThe solvent was removed in vacuo
  2. washwashed twice with ethyl acetate
  3. additionby adding a 45% aqueous NaOH solution
  4. extractionThe obtained suspension was extracted twice with ethyl acetate
  5. washThe combined phases were washed with brine
  6. dry with materialdried (Na2SO4)
  7. customthe solvent was removed in vacuo
  8. customThe crude product was purified on a silica gel column

Sources & evidence

ORD record
ord-6953c2db88f54db089b8fcd14ec9d013
Source dataset
uspto-grants-2008_07
Patent number
US07399780B2

Reaction notes

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