Hydrochloric Acid → 1-Piperidin-4-yl-1H-pyrazole-4-carboxylic acid [5-(3,5-difluoro-benzenesulfonyl)-1H-indazol-3-yl]-amide

HRID 1641000Notes

Reaction equation

HRID 1641000 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19](=[O:60])[NH:20][C:21]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([S:30]([C:33]5[CH:38]=[C:37]([F:39])[CH:36]=[C:35]([F:40])[CH:34]=5)(=[O:32])=[O:31])[CH:28]=4)[N:23](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:22]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.CO>O1CCOCC1>[F:40][C:35]1[CH:34]=[C:33]([S:30]([C:27]2[CH:28]=[C:29]3[C:24](=[CH:25][CH:26]=2)[NH:23][N:22]=[C:21]3[NH:20][C:19]([C:17]2[CH:16]=[N:15][N:14]([CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)[CH:18]=2)=[O:60])(=[O:31])=[O:32])[CH:38]=[C:37]([F:39])[CH:36]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 667365354-{4-[5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-ylcarbamoyl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 249865421-Piperidin-4-yl-1H-pyrazole-4-carboxylic acid [5-(3,5-difluoro-benzenesulfonyl)-1H-indazol-3-yl]-amide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

The crude 4-{4-[5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-ylcarbamoyl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester was dissolved into 15 mL of 1,4-dioxane and added with 3 mL of 4M hydrochloric acid in 1,4-dioxane and stirred at room temperature overnight. Methanol was then added and the mixture stirred for additional 2 hours. The volatiles were removed under reduced pressure, the residue re-dissolved into ethyl acetate, washed with 10% ammonium hydroxide in water, dried over sodium sulfate and evaporated to dryness. The residue was stirred overnight with diethyl ether/methanol 95:5, filtered, washed with diethyl ether/methanol 9:1 then with diethyl ether and dried in oven at 60° C. affording 170 mg of the title compound.

Workup

  1. stirringthe mixture stirred for additional 2 hours
  2. customThe volatiles were removed under reduced pressure
  3. dissolutionthe residue re-dissolved into ethyl acetate
  4. washwashed with 10% ammonium hydroxide in water
  5. dry with materialdried over sodium sulfate
  6. customevaporated to dryness
  7. stirringThe residue was stirred overnight with diethyl ether/methanol 95:5
  8. filtrationfiltered
  9. washwashed with diethyl ether/methanol 9:1
  10. dry with materialwith diethyl ether and dried in oven at 60° C.

Sources & evidence

ORD record
ord-2f197553071f479d9f284318fa3f7eec
Source dataset
uspto-grants-2012_02
Patent number
US08114865B2

Reaction notes

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