Hydrochloric Acid → 5-amino-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile

HRID 242195Notes

Reaction equation

HRID 242195 reaction equation
C(O[C:4](=[C:6]([C:9]#[N:10])[C:7]#[N:8])[CH3:5])C.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][NH2:20])=[CH:15][CH:14]=1.NN.Cl>CCO>[NH2:10][C:9]1[N:19]([C:16]2[CH:17]=[CH:18][C:13]([O:12][CH3:11])=[CH:14][CH:15]=2)[N:20]=[C:4]([CH3:5])[C:6]=1[C:7]#[N:8]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 9321HydrazineHCID 77023(4-Methoxyphenyl)hydrazineHCID 79450(1-Ethoxyethylidene)malononitrile

Product 1

HCID 671200415-amino-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrileYield 90.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
105 °C

Procedure

To a stirred solution of 2-(1-ethoxyethylidene)malononitrile (1.00 g, 6.66 mmol) in EtOH (8 mL) was added (4-methoxyphenyl)hydrazine (1.29 g, 9.32 mmol). (Prior to use the hydrazine its HCl salt was washed with NaHCO3/CH2Cl2. The organic phase was concentrated and used directly.) The solution was heated to 105° C. in the microwave for 20 min. CH2Cl2 was added and the organic phase was washed with 1M HCl and the organic extract was washed with aqueous NaHCO3. The solution was dried using a phase separator and concentrated under reduced pressure to give 5-amino-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile (1.38 g, 85%) which was used as such in the next step. The procedure was adapted from J. Med. Chem. 2004, 47, 5894-5911.

Workup

  1. washwas washed with NaHCO3/CH2Cl2
  2. concentrationThe organic phase was concentrated
  3. additionCH2Cl2 was added
  4. washthe organic phase was washed with 1M HCl
  5. extractionthe organic extract
  6. washwas washed with aqueous NaHCO3
  7. customThe solution was dried
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-60cd323482e643bdbe1183d98b1166c6
Source dataset
uspto-grants-2014_02
Patent number
US08653112B2

Reaction notes

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