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HRID1674553

反应详情

EQUATION

反应方程式

HRID 1674553 的结构方程式

REACTANTS

反应物

4
结构：O=C(n1ccnc1)n1ccnc1
HCID68263

1,1'-Carbonylbis(1H-imidazole)

C7H6N4O

结构：C1CCC2=NCCCN2CC1
HCID81184

1,8-Diazabicyclo[5.4.0]undec-7-ene

C9H16N2

结构：NS(=O)(=O)C1CC1
HCID15765418

Cyclopropanesulfonamide

C3H7NO2S

结构：CC(C)(C)OC(=O)N[C@H]1CNCCC/C=C\[C@@H]2C[C@@]2(C(=O)O)NC(=O)[C@@H]2C[C@@H](O[Si](C)(C)C(C)(C)C)CN2C1=O
HCID86612089

未命名化合物

PRODUCTS

生成物

1
结构：CC(C)(C)OC(=O)N[C@H]1CN(C2CC2)CCC/C=C\[C@@H]2C[C@@]2(C(=O)NS(=O)(=O)C2CC2)NC(=O)[C@@H]2C[C@@H](O[Si](C)(C)C(C)(C)C)CN2C1=O
HCID68252750

未命名化合物

收率 53%

AUXILIARIES

试剂、催化剂与溶剂

1
结构：C1CCOC1
溶剂HCID8028

Tetrahydrofuran

C4H8O

PROCEDURE

实验过程

(1S,4R,6S,14S,18R)-7-cis-14-tert-Butoxycarbonylamino-18-(tert-butyldimethylsilyloxy)-2,15-dioxo-3,12,16-triazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid (490 mg, 0.79 mmol) was dissolved in 15 mL of THF and treated with CDI (179 mg, 1.10 mmol.). (Care was taken to avoid moisture by using oven dried glassware and maintaining a dry N2 atmosphere.) After refluxing the reaction mixture for two hours, it was cooled to rt and treated sequentially with cyclopropylsulfonamide (134 mg, 1.10 mmol.) and DBU (168 mg, 1.10 mmol.). After stirring overnight at rt, the THF was removed by rotary evaporation. The residue was dissolved in water and 1N HCl was added until the pH=5. This aqueous solution was extracted with EtOAc (3×). The combined EtOAc extracts were dried (MgSO4) and concentrated in vacuo to give the crude product. Purification by flash column, eluting with 3% methanol in methylene chloride, gave 300 mg (53%) of (1S,4R,6S,14S,18R)-[7-cis-4-Cyclopropanesulfonylaminocarbonyl-12-cyclopropyl-18-(tert-butyldimethylsilyloxy)-2,15-dioxo-3,12,16-triaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]carbamic acid, tert-butyl ester as a white solid: LC-MS (Phenomenex 10 μm C18 HPLC column: 3.0×50 mm length. Gradient: 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B. Gradient time: 2 min. Hold time: 1 min. Flow rate: 5 mL/min. Detector Wavelength: 220 nM. Solvent A: 10% MeOH/90% H2O/0.1% TFA. Solvent B: 10% H2O/90% MeOH/0.1% TFA.) (Retention time: 2.40 min), MS m/z 724 (M++1).

WORKUP

后处理

  1. customdried glassware
  2. temperaturemaintaining a dry N2 atmosphere
  3. temperature) After refluxing the reaction mixture for two hours
  4. customthe THF was removed by rotary evaporation
  5. dissolutionThe residue was dissolved in water
  6. addition1N HCl was added until the pH=5
  7. extractionThis aqueous solution was extracted with EtOAc (3×)
  8. dry with materialThe combined EtOAc extracts were dried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customto give the crude product
  11. customPurification by flash column
  12. washeluting with 3% methanol in methylene chloride