Hydrochloric Acid → N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-1-(piperidin-4-yl)-1H-pyrazole-4-carboxamide hydrochloride

HRID 512971

Reaction equation

HRID 512971 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]([OH:21])=O)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(Cl)(=O)C([Cl:25])=O.[F:28][C:29]1[CH:30]=[C:31]([CH:43]=[C:44]([F:46])[CH:45]=1)[CH2:32][C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][CH:41]=1)[NH:38][N:37]=[C:36]2[NH2:42].Cl>C(Cl)Cl.N1C=CC=CC=1.O1CCOCC1>[ClH:25].[F:28][C:29]1[CH:30]=[C:31]([CH:43]=[C:44]([F:46])[CH:45]=1)[CH2:32][C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][CH:41]=1)[NH:38][N:37]=[C:36]2[NH:42][C:19]([C:17]1[CH:16]=[N:15][N:14]([CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)[CH:18]=1)=[O:21]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 441342655-[(3,5-difluorophenyl)methyl]-1H-indazol-3-amineHCID 534858971-(1-((tert-butoxy)carbonyl)piperidin-4-yl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 68671266N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-1-(piperidin-4-yl)-1H-pyrazole-4-carboxamide hydrochlorideYield 36.2%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

1-[1-(tert-butoxycarbonyl)piperidin-4-yl]-1H-pyrazole-4-carboxylic acid (134 mg, 0.45 mmol) and oxalyl chloride (0.6 mmol) were stirred in DCM dry (5 mL) at room temperature overnight. Volatiles were evaporated and the residue dissolved in dry pyridine (5 mL) at 0° C. A solution of 5-(3,5-difluoro-benzyl)-1H-indazol-3-ylamine (100 mg, 0.38 mmol) in dry pyridine (2 mL) was added to the cooled reaction mixture. After 1 hour, reaction was quenched with NaHCO3 sat. sol and extracted with ethyl acetate. Collected organic phases were dried over Na2SO4, filtered and evaporated to dryness. Residue was purified by column chromatography over silica gel (DCM/EtOH/NH3 5N in MeOH=1000/50/1) affording 87 mg of Boc-protected derivative which was dissolved in 2 mL of dioxane and treated with 0.4 mL of 4M HCl in dioxane. Volatiles were evaporated affording 65 mg of the title compound.

Workup

  1. customdry (5 mL) at room temperature overnight
  2. customVolatiles were evaporated
  3. dissolutionthe residue dissolved in dry pyridine (5 mL) at 0° C
  4. customreaction
  5. customwas quenched with NaHCO3 sat. sol
  6. extractionextracted with ethyl acetate
  7. dry with materialCollected organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customResidue was purified by column chromatography over silica gel (DCM/EtOH/NH3 5N in MeOH=1000/50/1)
  11. customaffording 87 mg of Boc-protected derivative which
  12. customVolatiles were evaporated

Sources & evidence

ORD record
ord-95652620fd9a42f397083af5471eabca
Source dataset
uspto-grants-2015_08
Patent number
US09102662B2

Linked notes

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