Triethylamine → HCID 46197349, compound

HRID 383558Notes

Reaction equation

HRID 383558 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:4]=1[NH:10][NH2:11].C(O[CH:15]=[C:16]([C:19]#[N:20])[C:17]#[N:18])C.C(N(CC)CC)C>C(O)C>[NH2:20][C:19]1[N:10]([C:4]2[C:3]([F:2])=[CH:8][CH:7]=[CH:6][C:5]=2[F:9])[N:11]=[CH:15][C:16]=1[C:17]#[N:18]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 671522-(Ethoxymethylene)propanedinitrileHCID 24721343(2,6-Difluorophenyl)hydrazine--hydrogen chloride (1/1)

Product 1

HCID 46197349HCID 46197349, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1-(2,6-difluorophenyl)hydrazine hydrochloride (12.38 g, 68.56 mmol) in anhydrous ethanol (70 mL) was added 2-(ethoxymethylene)malononitrile (8.791 g, 71.98 mmol) followed by triethylamine (10.01 mL, 71.98 mmol), and the contents stirred at RT for 10 min and then heated to reflux for 1.5 h. The contents were cooled to RT and solvents removed under reduced pressure. The resulting brown solid was stirred with 50 mL of water and 250 mL of EtOAc. The EtOAc layer was separated, washed with 50 mL of brine, dried and concentrated. The concentrated solid was stirred in 50 mL of hexanes for 5 min, filtered through a flitted funnel, and dried in a vacuum oven at 45° C. for 2 h to afford 5-amino-1-(2,6-difluorophenyl)-1H-pyrazole-4-carbonitrile as a brown solid. This material was used without further purification. MS (ES+): 221.1 (M+H)+. (B): A mixture of 5-amino-1-(2,6-difluorophenyl)-1H-pyrazole-4-carbonitrile (14 g, 64 mmol) in 50 mL of concentrated HCl was refluxed for 10 h. The reaction mixture was concentrated to half of its volume, cooled with an ice bath, pH adjusted to about 10 with 10 N NaOH, and extracted with 3×100 mL of EtOAc. The combined organic layers were washed with brine, dried and concentrated to afford 1-(2,6-difluorophenyl)-1H-pyrazol-5-amine as a brown amorphous solid. This material was used without further purification. MS (ES+): 196.1 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 1.5 h
  3. temperatureThe contents were cooled to RT
  4. customsolvents removed under reduced pressure
  5. stirringThe resulting brown solid was stirred with 50 mL of water and 250 mL of EtOAc
  6. customThe EtOAc layer was separated
  7. washwashed with 50 mL of brine
  8. customdried
  9. concentrationconcentrated
  10. stirringThe concentrated solid was stirred in 50 mL of hexanes for 5 min
  11. filtrationfiltered through a flitted funnel
  12. customdried in a vacuum oven at 45° C. for 2 h

Sources & evidence

ORD record
ord-5131a38b653f423aab2bda9e064a54d8
Source dataset
uspto-grants-2013_02
Patent number
US08367671B2

Reaction notes

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