반응 #992723

반응 방정식

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

수율 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

수율 58.4%

용매

THF

반응 조건

후처리

1. 1
   온도was heated
2. 2
   온도at reflux for 2 h under nitrogen
3. 3
   기타one peak of the intermediate (RT=5.37)
4. 4
   기타can be isolated
5. 5
   온도heated at 55° C. for 24 h
6. 6
   기타The solvent was evaporated
7. 7
   기타the residue partitioned between AcOEt ethyl acetate and acidic water (pH=3)
8. 8
   기타The crude material was purified by column chromatography (ethyl acetateAcOEt/CH2Cl2/pPetroleum ether, 1:1:1)
9. 9
   기타The residue was crystallized in diethyl ether
10. 10
    여과filtered
11. 11
    기타to give the target compound
12. 12
    기타This material was triturated in 3 mL of water
13. 13
    여과filtered
14. 14
    세척washed with water
15. 15
    기타dried overnight with the high vacuum pump

실험 절차

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).

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