Reaction #2487462

Reaction equation

6-[6-fluoro-5-methoxy-2-(thiophen-3-yl)indol-1-ylmethyl]pyridine-2-carboxamide

phosphoryl chloride

→

title compound

Yield 42.6%

6-[6-Fluoro-5-methoxy-2-(thiophen-3-yl)indol-1-ylmethyl]pyridine-2-carbonitrile

Yield 42.6%

Solvents

N,N-dimethylformamide

Conditions

Workup

1. 1
   Temperaturecooling
2. 2
   OtherThe reaction mixture was quenched with a saturated aqueous sodium hydrogen carbonate solution (10 mL)
3. 3
   workup.ADDITIONEthyl acetate and water were then added to the mixture
4. 4
   Otherto separate the organic layer
5. 5
   WashThe organic layer was washed with saturated brine
6. 6
   Dryingdried over anhydrous sodium sulfate
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   OtherThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

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).

Source