تفاعل #992723

معادلة التفاعل

cyclopropylsulfonamide

cyclopropylsulfonamide

29

17-[3-(4-cyclopropylthiazol-2-yl)-6-methoxy-isoquinolin-1-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid

1,1′-carbonyldiimidazole

DBU

→

target compound 30

المردود 58.4%

N-[17-[3-(4-cyclopropylthiazol-2-yl)-6-methoxyisoquinolin-1-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide

المردود 58.4%

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةwas heated
2. 2
   درجة الحرارةat reflux for 2 h under nitrogen
3. 3
   أخرىone peak of the intermediate (RT=5.37)
4. 4
   أخرىcan be isolated
5. 5
   درجة الحرارةheated at 55° C. for 24 h
6. 6
   أخرىThe solvent was evaporated
7. 7
   أخرىthe residue partitioned between AcOEt ethyl acetate and acidic water (pH=3)
8. 8
   أخرىThe crude material was purified by column chromatography (ethyl acetateAcOEt/CH2Cl2/pPetroleum ether, 1:1:1)
9. 9
   أخرىThe residue was crystallized in diethyl ether
10. 10
    ترشيحfiltered
11. 11
    أخرىto give the target compound
12. 12
    أخرىThis material was triturated in 3 mL of water
13. 13
    ترشيحfiltered
14. 14
    غسيلwashed with water
15. 15
    أخرىdried overnight with the high vacuum pump

الإجراء التجريبي

A mixture of 29 (91 mg, 0.14 mmol) and 1,1′-carbonyldiimidazole (CDI) (47 mg, 0.29 mmol) in dry THF (7 mL) was heated at reflux for 2 h under nitrogen. LCMS analysis shows one peak of the intermediate (RT=5.37). Optionally, the azalactone derivative, if desired, can be isolated. The reaction mixture was cooled to room temperature and cyclopropylsulfonamide (52 mg, 0.43 mmol) was added. Then, DBU (50 μL, 0.33 mmol) was added and the reaction mixture was stirred at room temperature for 1 h, and then heated at 55° C. for 24 h. The solvent was evaporated, and the residue partitioned between AcOEt ethyl acetate and acidic water (pH=3). The crude material was purified by column chromatography (ethyl acetateAcOEt/CH2Cl2/pPetroleum ether, 1:1:1). The residue was crystallized in diethyl ether, filtered to give the target compound contaminated with the cyclopropylsulfonamide. This material was triturated in 3 mL of water, filtered, washed with water and dried overnight with the high vacuum pump to give 60 mg (57%) of the target compound 30 as a slightly yellow powder: m/z=734 (M+H)+, 1H-NMR (CDCl3): 10.94 (s, 1H), 8.08 (d, J=8.6 Hz, 1H), 8.00 (s, 1H), 7.12-7.15 (m, 2H), 6.91 (s, 1H), 6.35 (s, 1H), 5.74-5.77 (m, 1H), 5.63-5.69 (m, 1H), 5.06 (t, J=10.4 Hz, 1H), 4.60 (t, J=12.3 Hz, 1H), 3.93 (s, 3H), 3.35-3.42 (m, 2H), 3.04 (s, 3H), 2.89-2.96 (m, 2H), 2.52-2.52 (m, 2H), 2.37-2.45 (m, 2H), 2.10-2.32 (m, 2H), 1.61-1.93 (m, 4H), 1.3-1.51 (m, 4H), 0.90-1.30 (m, 8H).

المصدر