Sodium hydride → HCID 136338406, compound

HRID 2245566Notes

Reaction equation

HRID 2245566 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][N:7]([S:10]([CH2:13][CH2:14][NH:15][C:16]([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[NH:23][C:22](=[O:27])[CH2:21]3)=[O:17])(=[O:12])=[O:11])[CH2:6][CH2:5]1.[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[CH:31][N:30]=1>CN(C)C=O.C(=O)([O-])O.[Na+]>[ClH:28].[C:35]([C:32]1[CH:33]=[CH:34][C:29]([C:21]2[C:20]3[C:24](=[CH:25][CH:26]=[C:18]([C:16]([NH:15][CH2:14][CH2:13][S:10]([N:7]4[CH2:6][CH2:5][N:4]([CH3:3])[CH2:9][CH2:8]4)(=[O:11])=[O:12])=[O:17])[CH:19]=3)[NH:23][C:22]=2[OH:27])=[N:30][CH:31]=1)#[N:36]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 68541190HCID 68541190, compound

Product 1

HCID 136338406HCID 136338406, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (0.026 g of 60% suspension in mineral oil, 0.65 mmol) was added to a cooled (0° C.) solution of N-{2-[(4-methylpiperazin-1-yl)sulfonyl]ethyl}-2-oxoindoline-5-carboxamide (0.120 g, 33 mmol) in N,N-dimethylformamide (5 mL). The reaction mixture was stirred at 0° C. for 10 min under an N2 atmosphere, followed by the addition of 2-chloro-5-cyanopyridine (0.050 g, 0.36 mmol) in N,N-dimethylformamide (2 mL). The reaction vessel was closed, immediately warmed up to 100° C., and the reaction was stirred at this temperature for 1 h. The cooled mixture was diluted with a saturated sodium hydrogen carbonate solution (5 mL) and concentrated in vacuo. The residue was suspended in methanol/dichloromethane (1:1), silica gel (˜2 g) was added and mixture was re-concentrated in vacuo. The solid residue was purified on a silica gel column using dichloromethane/methanol/aqueous NH3, (60:10:1), as the eluent. Fractions containing product were concentrated, the resulting orange foam was suspended in ethyl acetate (3 mL), and filtered to give 0.020 g (13% yield) of the title compound as the base. This material was dissolved in chloroform/methanol, (1:1), and treated with HCl in diethyl ether followed by addition of diethyl ether. The resulting yellow crystals were collected by filtration and washed with diethyl ether to afford 0.014 g (60% yield) of the title compound: 1H NMR (DMSO-d6, 300 MHz) δ 14.68 (br s, 1H), 10.94 (s, 1H), 10.55 (br s, 1H), 8.74 (br s, 1H), 8.59 (s, 1H), 8.00 (s, 1H), 7.86 (d, J=9.0 Hz, 1H), 7.70 (d, J=9.0 Hz, 1-H), 7.60 (d, J=8.1 Hz, 1H), 6.98 (d, J=8.1 Hz, 1H), 3.83-3.75 (m, 4H), 3.70-3.62 (m, 2H), 3.52-3.42 (m, 4H), 3.27-3.20 (m, 2H), 3.12-3.05 (m, 2H), 2.75 (s, 3H); MS (ES) m/z 469 (M++1).

Workup

  1. customThe reaction vessel was closed
  2. temperatureimmediately warmed up to 100° C.
  3. stirringthe reaction was stirred at this temperature for 1 h
  4. concentrationconcentrated in vacuo
  5. additionsilica gel (˜2 g) was added
  6. concentrationmixture was re-concentrated in vacuo
  7. customThe solid residue was purified on a silica gel column
  8. additionFractions containing product
  9. concentrationwere concentrated
  10. filtrationfiltered

Sources & evidence

ORD record
ord-57cc2180a43046cfbf52bda74bc32f36
Source dataset
uspto-grants-2010_03
Patent number
US07683067B2

Reaction notes

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