Реакция #88607

Уравнение реакции

2-(2-Bromoethoxy)tetrahydropyran

sodium iodide

9-benzenesulfonyl-3-bromo-5-(piperidin-4-yloxy)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile

→

title compound

Выход 33.5%

9-Benzenesulfonyl-3-bromo-5-{1-[2-(tetrahydropyran-2-yloxy)-ethyl]-piperidin-4-yloxy}-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile

Выход 33.5%

Растворители

acetonitrile

Условия реакции

Обработка

1. 1
   КонцентрированиеThe resultant residue was concentrated in-vacuo
2. 2
   workup.DISSOLUTIONthen dissolved in dichloromethane
3. 3
   workup.ADDITIONdiluted with 1N aqueous sodium carbonate (50 mL)
4. 4
   Экстракцияextracted with dichloromethane (3×50 mL)
5. 5
   СушкаThe combined organic layer was dried (Na2SO4)
6. 6
   Фильтрацияfiltered
7. 7
   Другоеevaporated in-vacuo
8. 8
   Другоеthe resultant residue purified by flash chromatography (silica, 40 g column, ISCO, 0-30% ethyl acetate in dichloromethane)

Методика

To a suspension of 9-benzenesulfonyl-3-bromo-5-(piperidin-4-yloxy)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (789 mg, 1.54 mmol) in acetonitrile (50 mL) was added sodium iodide (46 mg, 0.31 mmol) and the resultant suspension sonicated for 5 minutes. 2-(2-Bromoethoxy)tetrahydropyran (483 mg, 2.31 mmol) was added and the reaction mixture was heated to 50° C. for 48 hours. The resultant residue was concentrated in-vacuo then dissolved in dichloromethane, diluted with 1N aqueous sodium carbonate (50 mL) and extracted with dichloromethane (3×50 mL). The combined organic layer was dried (Na2SO4), filtered, evaporated in-vacuo and the resultant residue purified by flash chromatography (silica, 40 g column, ISCO, 0-30% ethyl acetate in dichloromethane) to afford the title compound as a pale yellow solid (330 mg, 33%). 1H NMR (300 MHz, CDCl3): 9.54 (s, 1H), 8.76 (d, J=2.3 Hz, 1H), 8.65 (d, J=2.3 Hz, 1H), 8.23-8.22 (m, 2H), 7.64-7.64 (m, 1H), 7.53-7.50 (m, 2H), 5.13-5.11 (m, 1H), 4.59 (t, J=3.5 Hz, 1H), 3.87-3.86 (m, 2H), 3.54-3.52 (m, 2H), 2.99 (d, J=11.6 Hz, 2H), 2.67 (t, J=6.0 Hz, 2H), 2.35 (t, J=11.3 Hz, 2H), 2.22 (d, J=12.3 Hz, 2H), 2.03-1.99 (m, 2H), 1.87-1.47 (m, 6H).

Источник