Hydrochloric Acid → 4-(5-Amino-3-tert-butyl-pyrazol-1-yl)-piperidine-1-carboxylic acid benzyl ester

HRID 75595Notes

Reaction equation

HRID 75595 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([NH:17][NH2:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:19][C:20]([CH3:27])([CH3:26])[C:21](=O)[CH2:22][C:23]#[N:24].Cl>CCO>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([N:17]2[C:23]([NH2:24])=[CH:22][C:21]([C:20]([CH3:27])([CH3:26])[CH3:19])=[N:18]2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 108871Pentanenitrile, 4,4-dimethyl-3-oxo-HCID 21098319Benzyl 4-hydrazinylpiperidine-1-carboxylate

Product 1

HCID 866866934-(5-Amino-3-tert-butyl-pyrazol-1-yl)-piperidine-1-carboxylic acid benzyl esterYield 21.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A yellow solution of Intermediate 16a (1.80 g, 7.22 mmol), 4,4-dimethyl-3-oxopentanenitrile (1.08 g, 8.66 mmol), and HCl (4M in dioxane, 2.70 mL, 10.8 mmol) in EtOH (25 mL) was stirred at reflux for 4 h. The cooled solution was applied to an SCX-2 cartridge (50 g), washed with MeOH (100 mL). The product was eluted with 2M NH3 in MeOH (100 mL); concentration in vacuo left a yellow oil (772 mg). FCC, using 0-5% MeOH in DCM, gave the title compound as a yellow gum (550 mg, 21%). LCMS (Method 3): Rt 2.88 min, m/z 357 [MH+].

Workup

  1. temperatureat reflux for 4 h
  2. washwashed with MeOH (100 mL)
  3. washThe product was eluted with 2M NH3 in MeOH (100 mL)
  4. concentrationconcentration in vacuo
  5. waitleft a yellow oil (772 mg)

Sources & evidence

ORD record
ord-77934c878f7c413c860c4bda75484783
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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