(Methoxymethylene)malononitrile → 5-amino-1-(2-methoxyphenyl)-1H-pyrazole-4-carbonitrile

HRID 2424763Notes

Reaction equation

HRID 2424763 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][NH2:11].CO[CH:14]=[C:15]([C:18]#[N:19])[C:16]#[N:17].C[O-].[Na+]>C(O)C>[NH2:19][C:18]1[N:10]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[O:3][CH3:2])[N:11]=[CH:14][C:15]=1[C:16]#[N:17]

Participants

5

Reactant 3

HCID 69599(Methoxymethylene)malononitrileHCID 28494452-Methoxyphenylhydrazine HydrochlorideHCID 10942334Sodium Methoxide

Product 1

HCID 121505605-amino-1-(2-methoxyphenyl)-1H-pyrazole-4-carbonitrileYield 53%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1-(2-methoxyphenyl)hydrazine hydrogen chloride (3 g, 0.017 mol) in ethanol (50 mL) was added 2-(methoxymethylene)malononitrile (1.89 g, 0.9 eq.) and sodium methoxide (1.92 g, 2.1 eq). The reaction mixture was heated at reflux for 18 h and concentrated. The reaction mixture was partitioned between brine and ethyl acetate. The organic layer was separated, dried with magnesium sulfate, filtered and concentrated. MPLC Biotage chromatography eluting with 20-60% ethyl acetate/hexanes afforded the title compound in 53% yield (1.9 g). 400 MHz 1H NMR (CDCl3) δ 7.64 (m, 1 H), 7.40 (m, 2H), 7.08 (m,2H), 4.51 (bs, 2H), 3.87 (s, 3 H); MS: (M+H m/z=215.2).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 18 h
  3. concentrationconcentrated
  4. customThe reaction mixture was partitioned between brine and ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washMPLC Biotage chromatography eluting with 20-60% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-87745b1b7aba427580d6ec3c231f052f
Source dataset
uspto-grants-2011_06
Patent number
US07964607B2

Reaction notes

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