1,1'-Carbonyldiimidazole → (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

HRID 1674553Notes

Reaction equation

HRID 1674553 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:27](=[O:28])[N:26]2[C@@H:22]([CH2:23][C@@H:24]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH2:25]2)[C:21](=[O:37])[NH:20][C@@:19]2([C:38](O)=[O:39])[C@@H:17]([CH2:18]2)[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][NH:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:53]1([S:56]([NH2:59])(=[O:58])=[O:57])[CH2:55][CH2:54]1.[CH2:60]1[CH2:70][CH2:69]N2C(=NCCC2)CC1>C1COCC1>[CH:53]1([S:56]([NH:59][C:38]([C@@:19]23[CH2:18][C@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][N:11]([CH:70]2[CH2:60][CH2:69]2)[CH2:10][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])[C:27](=[O:28])[N:26]2[C@@H:22]([CH2:23][C@@H:24]([O:29][Si:30]([C:33]([CH3:35])([CH3:36])[CH3:34])([CH3:31])[CH3:32])[CH2:25]2)[C:21](=[O:37])[NH:20]3)=[O:39])(=[O:58])=[O:57])[CH2:55][CH2:54]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 86612089(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

Product 1

HCID 68252750(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 esterYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(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

  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

Sources & evidence

ORD record
ord-2c8e7e1899044345b8cdcbbb28d97843
Source dataset
uspto-grants-2011_08
Patent number
US08003604B2

Reaction notes

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