Cyanoacetamide → benzyl 4-(5-amino-4-carbamoyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 2196555Notes

Reaction equation

HRID 2196555 reaction equation
[C:1]([CH2:3][C:4]([NH2:6])=[O:5])#[N:2].[O-]CC.[Na+].Br[C:12](=[N:17][NH:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:26])[CH2:21][CH2:20]1)[C:13]([F:16])([F:15])[F:14]>CCO>[NH2:2][C:1]1[N:18]([CH:19]2[CH2:20][CH2:21][N:22]([C:25]([O:27][CH2:28][C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[O:26])[CH2:23][CH2:24]2)[N:17]=[C:12]([C:13]([F:16])([F:15])[F:14])[C:3]=1[C:4](=[O:5])[NH2:6]

Participants

5

Reactant 3

HCID 7898CyanoacetamideHCID 2723922Sodium ethoxideHCID 72576664Benzyl 4-(2-(1-bromo-2,2,2-trifluoroethylidene)hydrazinyl)piperidine-1-carboxylate

Product 1

HCID 59843238benzyl 4-(5-amino-4-carbamoyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)piperidine-1-carboxylateYield 38.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a stirred solution of 2-Cyanoacetamide (520 mg, 6.19 mmol) in EtOH (8.6 mL) at room temperature was added Sodium ethoxide (21% in EtOH, 1.6 mL, 4.13 mmol). A solution of 111 (842 mg, 2.063 mmol) in EtOH (1.7 mL) was added dropwise and the resulting suspension was allowed to stir for 10 min at room temperature, then for 2 h at 80° C. The solvent was removed and after the usual work-up the crude material was purified via Biotage (10% to 40% EtOAc/Hexane; 25S column) to give 117 (327 mg, 38.5% yield) as an orange solid. LRMS (ESI): calc.411.4; found 412.1 (MH)+.

Workup

  1. waitfor 2 h at 80° C
  2. customThe solvent was removed
  3. customafter the usual work-up the crude material was purified via Biotage (10% to 40% EtOAc/Hexane; 25S column)

Sources & evidence

ORD record
ord-d18d63c0c0614f4fa2cb6742ca1cb939
Source dataset
uspto-grants-2012_12
Patent number
US08338437B2

Reaction notes

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