Cesium carbonate → HCID 86587528, compound

HRID 1835127Notes

Reaction equation

HRID 1835127 reaction equation
[CH2:1]([C:3]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([C:11]([NH2:13])=[O:12])[NH:5][N:4]=1)[CH3:2].CC1C=CC(S(O[CH2:25][C@@H:26]2[CH2:30][CH2:29][CH2:28][N:27]2[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])(=O)=O)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[NH2:13][C:11]([C:6]1[C:7]([N+:8]([O-:10])=[O:9])=[C:3]([CH2:1][CH3:2])[N:4]([CH2:25][C@@H:26]2[CH2:30][CH2:29][CH2:28][N:27]2[C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[N:5]=1)=[O:12]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11783214tert-Butyl (2S)-2-(((4-methylbenzene-1-sulfonyl)oxy)methyl)pyrrolidine-1-carboxylateHCID 178438045HCID 178438045, compound

Product 1

HCID 86587528HCID 86587528, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of 3-ethyl-4-nitro-1H-pyrazole-5-carboxamide (8.20 g, 44.6 mmol, prepared using procedure in WO9849166), tert-butyl (2S)-2-({[(4-methylphenyl)sulfonyl]oxy}methyl)-1-pyrrolidinecarboxylate (17.4 g, 49.0 mmol, prepared using procedure in WO9926944) and cesium carbonate (16.0 g, 49.2 mmol) in N,N-dimethylformamide (100 ml) was stirred at 20° C. for 4 days and then at 50° C. for 18 h. The reaction mixture was concentrated in vacuo and the residue was partitioned between EtOAc (300 ml) and water (300 ml). The phases were separated, and the aqueous layer extracted with further EtOAc (2×200 ml). The organic phases were combined, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was partially purified by column chromatography (DCM/MeOH, 100:0-91:9) and then the regioisomers were separated by further column chromatography (Et2O/EtOAc, 100:0-50:50) to afford the title compound of preparation 34 (1.23 g, 3.35 mmol, 7.5%); mp 68-75° C.

Workup

  1. waitat 50° C. for 18 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue was partitioned between EtOAc (300 ml) and water (300 ml)
  4. customThe phases were separated
  5. extractionthe aqueous layer extracted with further EtOAc (2×200 ml)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was partially purified by column chromatography (DCM/MeOH, 100:0-91:9)
  10. customthe regioisomers were separated by further column chromatography (Et2O/EtOAc, 100:0-50:50)
  11. customto afford

Sources & evidence

ORD record
ord-798f623746554bdba3a44008914d8a8e
Source dataset
uspto-grants-2004_08
Patent number
US06770645B2

Reaction notes

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