Potassium Carbonate → (R)-N-(5-((3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

HRID 43004Notes

Reaction equation

HRID 43004 reaction equation
O[CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][C@@H:7]([NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])[CH2:6]2.S(Cl)(Cl)=O.[F:23][C:24]([F:35])([F:34])[C:25]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[NH:27][N:26]=1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[F:33][C:30]([F:31])([F:32])[C:28]1[CH:29]=[C:25]([C:24]([F:23])([F:34])[F:35])[N:26]([CH2:2][C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][CH:11]=2)[CH2:8][C@@H:7]([NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])[CH2:6]3)[N:27]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 5189913,5-Bis(trifluoromethyl)pyrazoleHCID 67025426(R)-N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

Product 1

HCID 44511398(R)-N-(5-((3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideYield 2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (50 mg, 0.19 mmol) was dissolved in DCM (5 mL) and cooled to 0° C. before thionyl chloride (110 mg, 0.93 mmol) was added. The reaction mixture was stirred at room temperature for 1 h before being concentrated to dryness. The whole was dissolved in DMF (3 mL) to this was added 3,5-bis(trifluoromethyl)-1H-pyrazole (38 mg 0.19 mmol) followed by potassium carbonate (51 mg, 0.37 mmol). The reaction mixture was heated to 60° C. for 2 h before being quenched with water (2 mL) and the organics extracted with EtOAc (3×5 mL). The combined organics were washed with brine, dried (MgSO4) and concentrated under reduced pressure. Purification by preparative acidic HPLC gave (R)—N-(5-((3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (1.7 mg, 3.7 μmol, 2.0%). MS (ESI): m/z [M+H]+ 456.1

Workup

  1. additionwas added
  2. concentrationbefore being concentrated to dryness
  3. dissolutionThe whole was dissolved in DMF (3 mL) to
  4. temperatureThe reaction mixture was heated to 60° C. for 2 h
  5. custombefore being quenched with water (2 mL)
  6. extractionthe organics extracted with EtOAc (3×5 mL)
  7. washThe combined organics were washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated under reduced pressure
  10. customPurification by preparative acidic HPLC

Sources & evidence

ORD record
ord-ea8d1c458eaa4c4896dffe3ab43bb317
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

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