Phosphorus oxychloride → HCID 86703283, compound

HRID 2409964Notes

Reaction equation

HRID 2409964 reaction equation
[CH:1]1([C:4]2[CH:12]=[C:11]3[C:7]([C:8]([CH2:19][C:20]4[N:25]=[C:24]([C:26]([NH2:28])=O)[CH:23]=[CH:22][CH:21]=4)=[C:9]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[NH:10]3)=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH:1]1([C:4]2[CH:12]=[C:11]3[C:7]([C:8]([CH2:19][C:20]4[N:25]=[C:24]([C:26]#[N:28])[CH:23]=[CH:22][CH:21]=4)=[C:9]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[NH:10]3)=[CH:6][CH:5]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 68184812HCID 68184812, compound

Product 1

HCID 86703283HCID 86703283, compoundYield 72.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-(6-cyclopropyl-2-phenyl-1H-indol-3-ylmethyl)pyridine-2-carboxamide (137 mg) in N,N-dimethylformamide (1.5 mL) was added dropwise phosphoryl chloride (0.051 mL) under ice-cooling. This mixture was stirred for 50 minutes under ice-cooling. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (94.4 mg). 1H-NMR (CDCl3) δ ppm: 0.69-0.77 (2H, m), 0.92-1.03 (2H, m), 1.97-2.07 (1H, m), 4.46 (2H, s), 6.86 (1H, dd, J=1.5, 8.3 Hz), 7.11-7.17 (1H, m), 7.21-7.32 (2H, m), 7.33-7.64 (7H, m), 8.09 (1H, br s).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-bfde271336244d618ffea76d387d2e5d
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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