Hydrochloric Acid → 1-(6-methylpyridin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-5-amine

HRID 1930356Notes

Reaction equation

HRID 1930356 reaction equation
Cl.[NH:2]([C:4]1[CH:5]=[CH:6][C:7]([CH3:10])=[N:8][CH:9]=1)[NH2:3].[F:11][C:12]([F:19])([F:18])[C:13](=O)[CH2:14][C:15]#[N:16].Cl>C(O)C>[CH3:10][C:7]1[N:8]=[CH:9][C:4]([N:2]2[C:15]([NH2:16])=[CH:14][C:13]([C:12]([F:19])([F:18])[F:11])=[N:3]2)=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 138435404,4,4-Trifluoro-3-oxobutanenitrileHCID 248205115-Hydrazinyl-2-methylpyridine--hydrogen chloride (1/1)

Product 1

HCID 690362941-(6-methylpyridin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-5-amineYield 17.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 5-hydrazinyl-2-methylpyridine hydrochloride (5.0 g, 31 mmol) and 4,4,4-trifluoro-3-oxo-butyronitrile (9.0 g, 65 mmol) in ethanol (50 mL) was treated with cone HCl (5.0 mL, 60 mmol) and the resultant mixture was heated to reflux overnight. The solvent was removed in vacuo and the residue was dissolved in EtOAc and neutralized with saturated Na2CO3 solution. The organic layer was dried (Na2SO4), concentrated in vacuo and purified by pre-HPLC to give 2-(6-methyl-pyridin-3-yl)-5-trifluoromethyl-2H-pyrazol-3-ylamine (1.3 g, 10% yield over 2 steps). 1HNMR (400 MHz, CDCl3) δ 9.17 (d, J=1.6 Hz, 1 H), 8.40 (dd, J=8.4, 2.4 Hz, 1 H), 7.62 (d, J=8.4 Hz, 1 H), 5.97 (s, 1 H), 2.80 (s, 3 H); MS (ESI) m/z: 243.2 (M+H+).

Workup

  1. temperatureto reflux overnight
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in EtOAc and neutralized with saturated Na2CO3 solution
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by pre-HPLC

Sources & evidence

ORD record
ord-4a5b59f70b284019bbae35f0737bd4af
Source dataset
uspto-grants-2012_05
Patent number
US08188113B2

Reaction notes

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