Thionyl Chloride → (R)-N-(5-((4-(2-hydroxyethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

HRID 43002Notes

Reaction equation

HRID 43002 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:34])([F:33])[C:25]1[C:29]([CH2:30][CH2:31][OH:32])=[CH:28][NH:27][N:26]=1.[H-].[Na+]>C(Cl)Cl.CN(C=O)C>[OH:32][CH2:31][CH2:30][C:29]1[C:25]([C:24]([F:34])([F:33])[F:23])=[N:26][N:27]([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)[CH:28]=1

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 24758Sodium hydrideHCID 67025426(R)-N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideHCID 178520360HCID 178520360, compound

Product 1

HCID 44555551(R)-N-(5-((4-(2-hydroxyethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideYield 18.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

(R)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (45 mg, 0.17 mmol) was dissolved in DCM (5 mL) and thionyl chloride (99 mg, 0.83 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 (2 mL) and added to a solution of 2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)ethanol (30 mg, 0.17 mmol) in DMF (2 mL) which had been treated with sodium hydride (8 mg, 0.33 mmol) for 15 min. The reaction mixture was heated to 65° C. for 3 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 basic HPLC gave (R)—N-(5-((4-(2-hydroxyethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (13.6 mg, 0.032 mmol, 18.9%). MS (ESI): m/z [M+H]+ 432.5

Workup

  1. concentrationbefore being concentrated to dryness
  2. dissolutionThe whole was dissolved in DMF (2 mL)
  3. temperatureThe reaction mixture was heated to 65° C. for 3 h
  4. custombefore being quenched with water (2 mL)
  5. extractionthe organics extracted with EtOAc (3×5 mL)
  6. washThe combined organics were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customPurification by preparative basic HPLC

Sources & evidence

ORD record
ord-e8814ec407714c5797bf6c1629cbde51
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

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