Sodium Chloride → HCID 135462020, compound

HRID 2245557Notes

Reaction equation

HRID 2245557 reaction equation
[H-].[Na+].[O:3]=[C:4]1[CH2:12][C:11]2[C:6](=[CH:7][C:8]([C:13]#[N:14])=[CH:9][CH:10]=2)[NH:5]1.[Cl:15][C:16]1[N+:21]([O-])=[CH:20][C:19]([C:23]([N:25]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]2)=[O:24])=[CH:18][CH:17]=1.[Cl-].[Na+].P(Cl)(Cl)Cl>CN(C)C=O.C(=O)([O-])O.[Na+].C(Cl)(Cl)Cl.C(OCC)(=O)C.C(#N)C>[ClH:15].[OH:3][C:4]1[NH:5][C:6]2[C:11]([C:12]=1[C:16]1[CH:17]=[CH:18][C:19]([C:23]([N:25]3[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]3)=[O:24])=[CH:20][N:21]=1)=[CH:10][CH:9]=[C:8]([C:13]#[N:14])[CH:7]=2

Participants

10

Reactant 5

HCID 5234Sodium Chloride2×HCID 24387Phosphorus trichlorideHCID 24758Sodium hydrideHCID 27733482-Oxindole-6-carbonitrileHCID 11334324HCID 11334324, compound

Product 1

HCID 135462020HCID 135462020, compoundYield 15%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolventHCID 516892Sodium BicarbonateSolvent2×HCID 21584013Chloroform ethylacetateSolvent

Procedure

To a suspension of sodium hydride (97%, 0.024 g, 1.0 mmol) in N,N-dimethylformamide (1.5 mL) was added 2-oxoindoline-6-carbonitrile (0.119 g, 0.75 mmol). The resulting mixture was stirred for 5 min at room temperature and 1-[(6-chloro-1-oxidopyridin-3-yl)carbonyl]-4-methylpiperazine (0.128 g, 0.5 mmol) was added. The resulting reaction mixture was set under an N2 atmosphere and stirred for 20 h at room temperature. The N,N-dimethylformamide reaction solution was diluted with saturated aqueous sodium hydrogen carbonate and sodium chloride (2.0 g) was added followed by extractions with chloroform, ethyl acetate, and tetrahydrofuran. The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The remaining N,N-dimethylformamide was removed by co-evaporation with toluene (1×). The residual oil was dissolved in a chloroform/ethyl acetate, (5:1, 6 mL), and phosphorus trichloride (0.275 g, 2.0 mmol) was added. The reaction mixture was stirred for 60 min at 60° C., and was then cooled to room temperature. The mixture was poured into a saturated aqueous sodium hydrogen carbonate solution and sodium chloride (2.0 g) was added followed by extractions with chloroform (4×) and ethyl acetate (2×). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. Purification using preparative HPLC (XTerra®PrepMS C8 column 10 μm, 30×150 mm; 0.1 M NH4OAc buffer/acetonitrile, (80:20-20:80), as the eluent) gave 0.028 g (15% yield) of the title compound as the base. The base (0.025 g, 0.069 mmol) was dissolved in chloroform/methanol, (1:1), and treated with HCl in diethyl ether (1 M) at 0° C. The resulting yellow crystals were collected by filtration and washed with diethyl ether to obtain 0.020 g (70% yield) of the title compound: 1H NMR (DMSO-d6, 400 MHz) δ 10.61 (br s, 1H), 8.41 (s, 1H), 7.93 (br s, 1H), 7.80 (br s, 2H), 7.30 (br s, 1H), 7.15 (br s, 1H), 3.58 (br s, 4H), 2.40 (br s, 4H), 2.25 (s, 3H); MS (EI) m/z 362 (M++1).

Workup

  1. customThe resulting reaction mixture
  2. stirringstirred for 20 h at room temperature
  3. additionwas added
  4. extractionfollowed by extractions with chloroform, ethyl acetate, and tetrahydrofuran
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe remaining N,N-dimethylformamide was removed by co-evaporation with toluene (1×)
  8. additionwas added
  9. stirringThe reaction mixture was stirred for 60 min at 60° C.
  10. temperaturewas then cooled to room temperature
  11. additionwas added
  12. extractionfollowed by extractions with chloroform (4×) and ethyl acetate (2×)
  13. dry with materialThe combined organic extracts were dried (Na2SO4)
  14. concentrationconcentrated in vacuo
  15. customPurification

Sources & evidence

ORD record
ord-e68a6bb16073467f806832d0df8177e6
Source dataset
uspto-grants-2010_03
Patent number
US07683067B2

Reaction notes

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