Cyclohexylhydrazine hydrochloride → 5-Amino-1-cyclohexyl-1H-pyrazole-4-carbonitrile

HRID 1804530Notes

Reaction equation

HRID 1804530 reaction equation
Cl.[CH:2]1([NH:8][NH2:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C[O-].[Na+].C(O[CH2:16][CH:17]([C:20]#[N:21])[C:18]#[N:19])C>C(O)C>[NH2:21][C:20]1[N:8]([CH:2]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]2)[N:9]=[CH:16][C:17]=1[C:18]#[N:19]

Participants

5

Reactant 3

HCID 207836Cyclohexylhydrazine hydrochlorideHCID 296281Ethoxymethyl malononitrileHCID 10942334Sodium Methoxide

Product 1

HCID 6900055-Amino-1-cyclohexyl-1H-pyrazole-4-carbonitrileYield 66.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

To cyclohexylhydrazine hydrochloride (7.52 g, 50 mmol) generated above in 500 mL absolute ethanol was added sodium methoxide (Aldrich, 2.7 g, 50 mmol). The mixture was stirred briefly and ethoxymethylmalononitrile (Acros, 6.11 g, 50 mmol) was added in small portions over twenty minutes. The reaction mixture was then heated at 70° C. under argon overnight. On cooling, the reaction was concentrated and subjected to flash chromatography on silica gel (1:1 hexane:ethyl acetate) affording 6.3 g (66%) of a light brown solid. Compound 8: mp 99-103° C.; MS (ES+ calculated: 190.25; found: 191.15 M+H). HPLC (97% purity, retention time 11.135 minutes—Method A); 1H NMR (400 MHz, DMSO-d6) δ 7.50 (s, 1H), 6.49 (br s, 2H), 4.02 (m, 1H), 1.80-1.10 (m, 10H).

Workup

  1. temperatureOn cooling
  2. concentrationthe reaction was concentrated

Sources & evidence

ORD record
ord-70ebde533aa54cb193a83f9d51a86d82
Source dataset
uspto-grants-2013_01
Patent number
US08354414B2

Reaction notes

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