تفاعل #992724
ord-5793b2e7005d40eaa39161b87cc33511
معادلة التفاعل
المتفاعلات
الكواشف
المذيبات
ظروف التفاعل
المعالجة
- 1درجة الحرارةat reflux under nitrogen for 3 h
- 2أخرىThen, the reaction mixture was partitioned between AcOEt ethyl acetate and water
- 3تجفيفThe organic layer was dried (MgSO4)
- 4ترشيحfiltered
- 5أخرىevaporated
- 6أخرىThe residue was purified by column chromatography on silica gel (CH2Cl2/EtOAc, 95:05)
الإجراء التجريبي
A solution of 17-(3-chloro-6-methoxyisoquinolin-1-yloxy)-13-methyl-2,14-dioxo-3,13,15-triaza-tricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid (42), (80 mg, 0.147 mmol) and carbonyldiimidazol (48 mg, 0.295 mmol) in dry THF (25 mL) was stirred at reflux under nitrogen for 3 h. Then, the reaction mixture was cooled down to room temperature and cyclopropylsulfonamide (54 mg, 0.442 mmol) and DBU (52 mg, 0.34 mmol) were added. The resulting solution was stirred at 50° C. for 48 h. Then, the reaction mixture was partitioned between AcOEt ethyl acetate and water. The organic layer was dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica gel (CH2Cl2/EtOAc, 95:05) to give the title product contaminated with cyclopropylsulfonamide. This solid was triturated 10 min in water and filtered, washed with water, dried under high vacuum, triturated again in diethylether and filtered to give 37 mg (39%) of the title product 43 as a white powder: m/z=647 (M+H)+; 1H-NMR (CDCl3): 10.40 (br s, 1H), 7.95 (d, J=9.1 Hz, 1H), 7.55 (s, 1H), 7.15 (s, 1H), 7.10 (dd, J=9.12 Hz, 2.4 Hz, 1H), 6.90 (d, J=2.4 Hz, 1H), 5.85 (br s, 1H), 5.65 (dd, J=18.2 Hz, 8.0 Hz, 1H), 5.15 (t, J=10.0 Hz, 1H), 4.8 (t, J=7.2 Hz, 1H), 4.10 (dd, J=11.3 Hz, 3.8 Hz, 1H), 3.9 (s, 3H), 3.60-3.70 (m, 1H), 3.6 (d, J=11.3 Hz, 1H), 3.10-3.20 (m, 1H), 2.90-3.00 (m, 1H), 2.85 (s, 3H), 2.4-2.6 (m, 3H), 1.90-2.20 (m, 3H), 1.25-1.60 (m, 7H), 0.90-1.10 (m, 2H).