تفاعل #992725

ord-2b766884f590462b91db50bc405f6a8d

معادلة التفاعل

COc1ccc2c(OC3CC4C(=O)NC5(C(=O)O)CC5C=CCCCCN(C)C(=O)N4C3)nccc2c1Br
50
COc1ccc2c(OC3CC4C(=O)NC5(C(=O)O)CC5C=CCCCCN(C)C(=O)N4C3)nccc2c1Br
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
O=C(n1ccnc1)n1ccnc1
carbonyldiimidazole
NS(=O)(=O)C1CC1
cyclopropylsulfonamide
C1CCC2=NCCCN2CC1
DBU
COc1ccc2c(OC3CC4C(=O)NC5(C(=O)NS(=O)(=O)C6CC6)CC5C=CCCCCN(C)C(=O)N4C3)nccc2c1Br
title product 51
المردود 77.8%
COc1ccc2c(OC3CC4C(=O)NC5(C(=O)NS(=O)(=O)C6CC6)CC5C=CCCCCN(C)C(=O)N4C3)nccc2c1Br
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
المردود 77.8%

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    درجة الحرارةat reflux under nitrogen for 2 h
  2. 2
    أخرىcan be isolated
  3. 3
    درجة الحرارةcooled to room temperature
  4. 4
    أخرىThe reaction mixture was quenched with water
  5. 5
    استخلاصextracted with AcOEtethyl acetate
  6. 6
    تجفيفdried (MgSO4)
  7. 7
    ترشيحfiltered
  8. 8
    أخرىevaporated
  9. 9
    أخرىThe crude material was purified by column chromatography (CH2Cl2/EtOAc, 95:5)
  10. 10
    أخرىThe solid obtained
  11. 11
    أخرىwas triturated in water
  12. 12
    ترشيحfiltered
  13. 13
    أخرىdried under high vacuum
  14. 14
    أخرىtriturated in diethylether
  15. 15
    أخرىdried again under high vacuum

الإجراء التجريبي

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).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08012939B2uspto-grants-2011_09