Ammonia → HCID 59637298, compound

HRID 1843022Notes

Reaction equation

HRID 1843022 reaction equation
[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[C:12]([C:13](O)=[O:14])=[CH:11][C:10]([C:16]([F:19])([F:18])[F:17])=[N:9]2)=[CH:5][CH:4]=1.C[N:23](C=O)C.S(Cl)(Cl)=O.N>C(Cl)Cl.C(OCC)(=O)C.CCCCCC>[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[C:12]([C:13]([NH2:23])=[O:14])=[CH:11][C:10]([C:16]([F:19])([F:18])[F:17])=[N:9]2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 59637302HCID 59637302, compound

Product 1

HCID 59637298HCID 59637298, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 21226206Ethyl acetate hexaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (50 g, 0.16 mol) in DCM (750 mL), a catalytic amount of DMF was added and the mixture was cooled to 0° C. Thionyl chloride (61 mL, 0.83 mol) was added drop wise for 30 min at 0° C. The overall reaction mixture was heated to reflux and maintained for 2 h. Progress of the reaction was monitored by TLC (10% ethyl acetate/hexane, Rf˜0.4). On disappearance of the starting material, DCM was distilled off completely. Above prepared acid chloride was dissolved in DCM (500 mL) and added drop wise to aqueous ammonia solution (700 mL) at 0° C. The overall reaction mixture was allowed to stir for 1 h and the progress of the reaction was monitored by TLC (10% ethyl acetate/hexane, Rf˜0.7). On completion of the reaction, ice cold water (200 mL) was added and the product was extracted with ethyl acetate (2×200 mL). The combined organic layer was dried over sodium sulfate and concentrated under reduced pressure to yield 1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide as an off white solid (37 g, crude). Crude product obtained was directly used for the next step.

Workup

  1. temperatureThe overall reaction mixture was heated
  2. temperatureto reflux
  3. temperaturemaintained for 2 h
  4. distillationOn disappearance of the starting material, DCM was distilled off completely
  5. customAbove prepared acid chloride
  6. additionwas added
  7. extractionthe product was extracted with ethyl acetate (2×200 mL)
  8. dry with materialThe combined organic layer was dried over sodium sulfate
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-80afe485ef934532979268abfece87fb
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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