Réaction #992725

Équation de réaction

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

Rendement 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

Rendement 77.8%

Solvants

THF

Conditions de réaction

Traitement

1. 1
   Températureat reflux under nitrogen for 2 h
2. 2
   Autrecan be isolated
3. 3
   Températurecooled to room temperature
4. 4
   AutreThe reaction mixture was quenched with water
5. 5
   Extractionextracted with AcOEtethyl acetate
6. 6
   Séchagedried (MgSO4)
7. 7
   Filtrationfiltered
8. 8
   Autreevaporated
9. 9
   AutreThe crude material was purified by column chromatography (CH2Cl2/EtOAc, 95:5)
10. 10
    AutreThe solid obtained
11. 11
    Autrewas triturated in water
12. 12
    Filtrationfiltered
13. 13
    Autredried under high vacuum
14. 14
    Autretriturated in diethylether
15. 15
    Autredried again under high vacuum

Mode opératoire

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).

Source