Potassium Carbonate → (R)-N-(5-((4-(2-hydroxypropan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

HRID 43001Notes

Reaction equation

HRID 43001 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[C:29]([C:30]([OH:33])([CH3:32])[CH3:31])=[CH:28][NH:27][N:26]=1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[OH:33][C:30]([C:29]1[C:25]([C:24]([F:35])([F:34])[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)([CH3:32])[CH3:31]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 67025426(R)-N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideHCID 178458810HCID 178458810, compound

Product 1

HCID 44555608(R)-N-(5-((4-(2-hydroxypropan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (30 mg, 0.11 mmol) was dissolved in DCM (5 mL) and thionyl chloride (66 mg, 0.57 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 2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)propan-2-ol (21.6 mg, 0.11 mmol) was added followed by potassium carbonate (30.8 mg, 0.22 mmol). The reaction mixture was stirred at room temperature overnight 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-hydroxypropan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (9.6 mg, 0.022 mmol, 19.4%). MS (ESI): m/z [M+H]+ 446.5

Workup

  1. concentrationbefore being concentrated to dryness
  2. dissolutionThe whole was dissolved in DMF (2 mL)
  3. stirringThe reaction mixture was stirred at room temperature overnight
  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-a0d726bb004c40319d60c3962ede42b4
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

Loading…