Reacción #85430

Ecuación de reacción

3,4-Difluorobenzyl bromide

compound 141-F

N-(6-Methoxy-benzo[b]thiophen-2-yl)-pyridin-3-yl-sulfonamide

potassium tert-butoxide

→

compound 141-G

Rendimiento 66.0%

N-(3,4-Difluoro-benzyl)-N-(6-methoxy-benzo[b]thiophen-2-yl)-pyridin-3-yl-sulfonamide

Rendimiento 66.0%

Disolventes

THF

EtOAc

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added drop-wise
2. 2
   workup.STIRRINGthe reaction was stirred at ambient temperature for 18 h
3. 3
   Lavadowashed with 2N HCl, water, brine
4. 4
   Secadodried over Na2SO4
5. 5
   Filtraciónfiltered
6. 6
   Otrothe solvent evaporated under reduced pressure
7. 7
   OtroThe crude residue was purified by flash column chromatography (SiO2)
8. 8
   Lavadoeluting with a heptane-EtOAc gradient
9. 9
   Otroto afford an oily semi-solid, which
10. 10
    Otrowas further purified by reverse-phase semi-prep HPLC (Gemini, C-18 column; 100×30 mm I.D.; 5μ)
11. 11
    Lavadoeluting with a 55% to 75% MeCN—H2O gradient

Procedimiento

To a solution of compound 141-F (0.488 g; 1.52 mmol) in THF (15 mL) was added 1M potassium tert-butoxide (2.28 mL; 2.28 mmol) and the reaction mixture was stirred at ambient temperature for 30 min. 3,4-Difluorobenzyl bromide (0.409 g; 1.97 mmol), dissolved in THF (1.0 mL), was added drop-wise, and the reaction was stirred at ambient temperature for 18 h. The reaction was diluted with EtOAc, washed with 2N HCl, water, brine, dried over Na2SO4, filtered, the solvent evaporated under reduced pressure. The crude residue was purified by flash column chromatography (SiO2) eluting with a heptane-EtOAc gradient to afford an oily semi-solid, which was further purified by reverse-phase semi-prep HPLC (Gemini, C-18 column; 100×30 mm I.D.; 5μ) eluting with a 55% to 75% MeCN—H2O gradient to afford compound 141-G as a white solid (0.447 g, 66%). 1H-NMR (DMSO-d6): δ 3.76 (s, 3H), 4.89 (s, 2H), 6.93-6.96 (m, 1H), 7.11 (s, 1H), 7.19-7.20 (m, 1H), 7.34-7.43 (m, 3H), 7.60-7.62 (d, 1H), 7.70-7.73 (m, 1H), 8.21-8.24 (m, 1H), 8.93-8.96 (m, 2H); MS: m/z 447.0 (MH+).

Fuente