Реакция #992725

Уравнение реакции

50

17-(5-bromo-6-methoxyisoquinolin-1-yloxy)-13-methyl-2,14-dioxo-3,13,15-triazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid

carbonyldiimidazole

cyclopropylsulfonamide

DBU

→

title product 51

Выход 77.8%

N-[17-(5-bromo-6-methoxyisoquinolin-1-yloxy)-13-methyl-2,14-dioxo-3,13,15-triaza-tricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide

Выход 77.8%

Растворители

THF

Условия реакции

Обработка

1. 1
   Температураat reflux under nitrogen for 2 h
2. 2
   Другоеcan be isolated
3. 3
   Температураcooled to room temperature
4. 4
   ДругоеThe reaction mixture was quenched with water
5. 5
   Экстракцияextracted with AcOEtethyl acetate
6. 6
   Сушкаdried (MgSO4)
7. 7
   Фильтрацияfiltered
8. 8
   Другоеevaporated
9. 9
   ДругоеThe crude material was purified by column chromatography (CH2Cl2/EtOAc, 95:5)
10. 10
    ДругоеThe solid obtained
11. 11
    Другоеwas triturated in water
12. 12
    Фильтрацияfiltered
13. 13
    Другоеdried under high vacuum
14. 14
    Другоеtriturated in diethylether
15. 15
    Другоеdried again under high vacuum

Методика

A solution of 50 (151 mg, 0.257 mmol) and carbonyldiimidazole (162 mg, 0.437 mmol) in dry THF (10 mL) was stirred at reflux under nitrogen for 2 h. Optionally, the azalactone derivative, if desired, can be isolated. Then, the reaction mixture was cooled to room temperature and cyclopropylsulfonamide (58 mg, 0.482 mmol) and DBU (76 mg, 0.502 mmol) were added. The resulting solution was stirred at 50° C. for 12 h, then cooled to room temperature. The reaction mixture was quenched with water and extracted with AcOEtethyl acetate, dried (MgSO4), filtered and evaporated. The crude material was purified by column chromatography (CH2Cl2/EtOAc, 95:5). The solid obtained was triturated in water, filtered, dried under high vacuum, triturated in diethylether and dried again under high vacuum to give 138 mg (77%) of the title product 51 as a white powder: m/z=691 (M+H)+; 1H-NMR (CDCl3): 10.70 (br s, 1H), 8.12 (d, J=9.1 Hz, 1H), 7.97 (d, J=6.3 Hz, 1H), 7.54 (d, J=6.3 Hz, 1H), 7.21 (d, J=9.1 Hz, 1H), 6.70 (bs, 1H), 5.88 (bs, 1H), 5.74 (dd, J=17.3 Hz, 8.3 Hz, 1H), 5.16 (t, J=10.4 Hz, 1H), 4.74 (dd, J=9.4 Hz, 7.3 Hz, 1H), 4.11-3.98 (m, 4H), 3.69-3.55 (m, 2H), 3.27-3.10 (m, 1H), 3.02-2.89 (m, 1H), 2.83 (s, 3H), 2.58-2.35 (m, 3H), 2.29-2.13 (m, 1H), 2.11-1.92 (m, 2H), 1.75-0.76 (m, 9H).

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