Methanesulfonyl chloride → HCID 86729424, compound

HRID 521247Notes

Reaction equation

HRID 521247 reaction equation
[C:1]([CH2:3][C:4]1([N:11]2[CH:15]=[C:14]([C:16]([NH2:18])=[O:17])[C:13]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)=[N:12]2)[CH2:9][CH2:8][CH:7](O)[CH2:6][CH2:5]1)#[N:2].CS(Cl)(=O)=O.[N-:32]=[N+:33]=[N-:34].[Na+]>C(Cl)Cl.C([O-])(O)=O.[Na+].CN(C=O)C.O>[N:32]([CH:7]1[CH2:6][CH2:5][C:4]([N:11]2[CH:15]=[C:14]([C:16]([NH2:18])=[O:17])[C:13]([NH:19][C:20]3[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=3)=[N:12]2)([CH2:3][C:1]#[N:2])[CH2:9][CH2:8]1)=[N+:33]=[N-:34]

Participants

8

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 86729423HCID 86729423, compound

Product 1

HCID 86729424HCID 86729424, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 1-[1-(cyanomethyl)-4-hydroxycyclohexyl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide (75 mg, 0.21 mmol) in DCM (2 mL) at ambient temperature was added TEA (0.059 mL, 0.42 mmol), and methanesulfonyl chloride (0.020 mL, 0.25 mmol). The mixture was stirred at ambient temperature for 10 minutes. The mixture was diluted with saturated aqueous NaHCO3, and extracted with EtOAc. The organic layer was separated, washed with brine, dried over anhydrous MgSO4 and concentrated in vacuo. The crude residue (90 mg, 0.207 mmol) was diluted in DMF (1.0 mL), NaN3 (27 mg, 0.41 mmol) was added and the mixture was heated at 90° C. for 16 hours. The mixture was cooled to ambient temperature, diluted with H2O and extracted with EtOAc. The organic layer was separated, washed with brine, dried over anhydrous MgSO4 and concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 30-100% EtOAc/hexanes) to give the title compound as a mixture of two diasteromers (ratio 1:3), which was used without further purification.

Workup

  1. extractionextracted with EtOAc
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated in vacuo
  6. temperaturethe mixture was heated at 90° C. for 16 hours
  7. temperatureThe mixture was cooled to ambient temperature
  8. extractionextracted with EtOAc
  9. customThe organic layer was separated
  10. washwashed with brine
  11. dry with materialdried over anhydrous MgSO4
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by MPLC on silica gel (
  14. washa gradient elution of 30-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-3ad21a876b334e2ea1a60538c159003c
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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