Trifluoroacetic acid → HCID 24789148, compound

HRID 503945Notes

Reaction equation

HRID 503945 reaction equation
FC(F)(F)C(O)=O.C(O[C:13]([N:15]1[CH2:19][CH2:18][C@@H:17]([C:20]2[CH:25]=[CH:24][C:23]([S:26]([C:29]3[CH:30]=[C:31]4[C:35](=[CH:36][CH:37]=3)[NH:34][N:33]=[CH:32]4)(=[O:28])=[O:27])=[CH:22][CH:21]=2)[CH2:16]1)=O)(C)(C)C>C(Cl)Cl>[CH3:13][N:15]1[CH2:19][CH2:18][C@@H:17]([C:20]2[CH:21]=[CH:22][C:23]([S:26]([C:29]3[CH:30]=[C:31]4[C:35](=[CH:36][CH:37]=3)[NH:34][N:33]=[CH:32]4)(=[O:27])=[O:28])=[CH:24][CH:25]=2)[CH2:16]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66877530HCID 66877530, compound

Product 1

HCID 24789148HCID 24789148, compoundYield 57.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (3.4 mL) was added to a solution of (S)-3-[4-(1H-indazole-5-sulfonyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (193.4 mg, 0.452 mmol) in DCM (3.4 mL) under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and the residue was dissolved in acetonitrile (4 mL). Formaldehyde (37% in water, 0.181 mL) was added, under nitrogen atmosphere, to this material followed by sodiumcyanoborohydride (85 mg). The reaction mixture was stirred for 1.5 hour, and then a saturated solution of Na2CO3 was then added. The mixture was extracted with DCM, and the combined organic extracts were dried over Na2SO4, filtered, and evaporated under reduced pressure. The crude material was dissolved in HCl (2 M, 10 mL) and the resulting mixture was stirred for 8 hours. Solvent was evaporated under reduced pressure and the crude residue was purified via flash chromatography (DCM/MeOH/NH4OH) to give 89.2 mg of 5-[4-((S)-1-methyl-pyrrolidin-3-yl)-benzenesulfonyl]-1H-indazole which was treated with 1,4-dioxane (2 mL) and transformed into 83.3 mg of the corresponding hydrochloride salt by addition of HCl (4 M in 1,4-dioxane, 0.84 mL). MS (M+H)=342.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in acetonitrile (4 mL)
  3. additionFormaldehyde (37% in water, 0.181 mL) was added, under nitrogen atmosphere, to this material
  4. stirringThe reaction mixture was stirred for 1.5 hour
  5. additiona saturated solution of Na2CO3 was then added
  6. extractionThe mixture was extracted with DCM
  7. dry with materialthe combined organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. dissolutionThe crude material was dissolved in HCl (2 M, 10 mL)
  11. stirringthe resulting mixture was stirred for 8 hours
  12. customSolvent was evaporated under reduced pressure
  13. customthe crude residue was purified via flash chromatography (DCM/MeOH/NH4OH)

Sources & evidence

ORD record
ord-f47af548921e47708fb7a7b3d696f92d
Source dataset
uspto-grants-2010_08
Patent number
US07776910B2

Reaction notes

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