Dimethylformamide → (2S,4R)-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)-2-{4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidin-4-yl)carbonylpyrrolidine

HRID 1586745Notes

Reaction equation

HRID 1586745 reaction equation
CN(C)C=O.P(Cl)(Cl)(Cl)=O.[CH3:11][S:12]([O:15][C@H:16]1[CH2:20][N:19]([C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)=[O:22])[C@H:18]([C:34](O)=[O:35])[CH2:17]1)(=[O:14])=[O:13].[N:37]1[N:41]2[CH2:42][CH2:43][CH2:44][NH:45][C:40]2=[CH:39][CH:38]=1>O1CCCC1.O.C(OCC)(=O)C.C(N(CC)CC)C>[CH3:11][S:12]([O:15][C@H:16]1[CH2:20][N:19]([C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)=[O:22])[C@H:18]([C:34]([N:45]2[CH2:44][CH2:43][CH2:42][N:41]3[N:37]=[CH:38][CH:39]=[C:40]23)=[O:35])[CH2:17]1)(=[O:14])=[O:13]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 13502650trans-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)-L-prolineHCID 1356276294H,5H,6H,7H-pyrazolo(1,5-a)pyrimidine

Product 1

HCID 57038139(2S,4R)-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)-2-{4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidin-4-yl)carbonylpyrrolidineYield 75.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

To a mixture of N,N-dimethylformamide (1.20 ml) and tetrahydrofuran (2.4 ml) was added dropwise phosphorus oxychloride (1.25 ml) at -20° C. and the mixture was stirred at 5° C. for 5 minutes. To the mixture was added a solution of (2S,4R)-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)proline (4.0 g) in tetrahydrofuran (10 ml) under ice-cooling. The mixture was stirred at the same temperature for 30 minutes. To a solution of 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine (1.40 g) in tetrahydrofuran (20 ml) and water (10 ml) was added dropwise the solution obtained above with stirring under ice-cooling, keeping the pH to 8-10 with triethylamine. The mixture was stirred at the same condition for 1 hour. To the reaction mixture was added ethyl acetate (100 ml) and the organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively, dried over anhydrous magnesium sulfate and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of chloroform and methanol (19:1, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4R)-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)-2-{4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidin-4-yl)carbonylpyrrolidine (3.84 g).

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred at the same temperature for 30 minutes
  3. customobtained above
  4. stirringwith stirring under ice-
  5. temperaturecooling
  6. stirringThe mixture was stirred at the same condition for 1 hour
  7. washthe organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride successively
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customevaporated in vacuo
  10. customThe resulting residue was chromatographed on silica gel (100 g)
  11. washeluting with a mixture of chloroform and methanol (19:1, V/V)
  12. additionThe fractions containing the desired compound
  13. customwere collected
  14. customevaporated in vacuo

Sources & evidence

ORD record
ord-1b0b9e423691406080036bb7388cb7dc
Source dataset
uspto-grants-1993_06
Patent number
US05215983

Reaction notes

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