Phosphorus oxychloride → HCID 86707938, compound

HRID 2400280Notes

Reaction equation

HRID 2400280 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:21]3[CH:25]=[CH:24][S:23][CH:22]=3)[N:8]2[CH2:11][C:12]2[N:17]=[C:16]([C:18]([NH2:20])=O)[CH:15]=[CH:14][CH:13]=2)=[CH:4][C:3]=1[O:26][CH3:27].P(Cl)(Cl)(Cl)=O>CN(C)C=O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:21]3[CH:25]=[CH:24][S:23][CH:22]=3)[N:8]2[CH2:11][C:12]2[N:17]=[C:16]([C:18]#[N:20])[CH:15]=[CH:14][CH:13]=2)=[CH:4][C:3]=1[O:26][CH3:27]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 86707936HCID 86707936, compound

Product 1

HCID 86707938HCID 86707938, compoundYield 42.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-[6-fluoro-5-methoxy-2-(thiophen-3-yl)indol-1-ylmethyl]pyridine-2-carboxamide (165 mg) in N,N-dimethylformamide (2.1 mL) was added phosphoryl chloride (0.058 mL) under ice-cooling. This mixture was stirred for 50 minutes. The reaction mixture was quenched with a saturated aqueous sodium hydrogen carbonate solution (10 mL). Ethyl acetate and water were then added to the mixture to separate the organic layer. 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 (67 mg). 1H-NMR (CDCl3) δ ppm: 3.94 (3H, s), 5.47 (2H, s), 6.62 (1H, s), 6.80 (1H, d, J=8.3 Hz), 6.87 (1H, d, J=11.3 Hz), 7.10-7.30 (3H, m), 7.35-7.45 (1H, m), 7.59 (1H, d, J=7.7 Hz), 7.65-7.75 (1H, m).

Workup

  1. temperaturecooling
  2. customThe reaction mixture was quenched with a saturated aqueous sodium hydrogen carbonate solution (10 mL)
  3. additionEthyl acetate and water were then added to the mixture
  4. customto separate the organic layer
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-ac0e99b3c7a7457286dc5fc463d3bc1e
Source dataset
uspto-grants-2014_08
Patent number
US08796247B2

Reaction notes

Loading…