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

(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

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

ORD record

ord-e8814ec407714c5797bf6c1629cbde51

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536214B2