Potassium Carbonate → HCID 58230811, compound

HRID 43003Notes

Reaction equation

HRID 43003 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:42])([F:41])[C:25]1[C:29]2[CH2:30][N:31](C(OC(C)(C)C)=O)[CH2:32][CH2:33][C:28]=2[NH:27][N:26]=1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[F:42][C:24]([F:23])([F:41])[C:25]1[C:29]2[CH2:30][NH:31][CH2:32][CH2:33][C:28]=2[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)[N:26]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 56773879tert-Butyl 3-(trifluoromethyl)-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylateHCID 67025426(R)-N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

Product 1

HCID 58230811HCID 58230811, compoundYield 6.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (23 mg, 0.086 mmol) was dissolved in DCM (5 mL) and thionyl chloride (51 mg, 0.43 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) to this was added tert-butyl 3-(trifluoromethyl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate (25 mg, 0.086 mmol) followed by potassium carbonate (24 mg, 0.172 mmol). 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. The residue was treated with 1:1 TFA/DCM (2 mL) for 2 h before being concentrated to dryness. Purification by preparative basic HPLC gave (R)—N-(5-((3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (2.3 mg, 5.2 μmol, 6.1%). MS (ESI): m/z [M+H]+ 443.2

Workup

  1. concentrationbefore being concentrated to dryness
  2. dissolutionThe whole was dissolved in DMF (2 mL) to
  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. additionThe residue was treated with 1:1 TFA/DCM (2 mL) for 2 h
  10. concentrationbefore being concentrated to dryness
  11. customPurification by preparative basic HPLC

Sources & evidence

ORD record
ord-288ee48869734de598ba83ebf86e6bfe
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

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