Ammonia → 5-Methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carboxamide

HRID 2400564Notes

Reaction equation

HRID 2400564 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:15]([OH:17])=O)[CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH3:24]>ClCCl.CN(C=O)C.O1CCOCC1>[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:15]([NH2:24])=[O:17])[CH:3]=1

Participants

7

Reactant 3

HCID 222AmmoniaHCID 65578Oxalyl chlorideHCID 27470481-(4-Methylbenzyl)-5-methyl-1H-pyrazole-3-carboxylic acid2×

Product 1

HCID 595047015-Methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carboxamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mechanically stirred solution of 5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carboxylic acid (Intermediate B, 500 mg, 2.17 mmol) in dichloromethane (15 mL) was added dropwise oxalylchloride (950 μL, 10.9 mmol) and one drop DMF. After stirring at rt for 1 h, all volatiles were removed in vacuo. The crude acid chloride thus obtained was re-dissolved in dioxane (10 mL) and added dropwise to aqueous ammonia (33%, 6.4 mL) at 0° C. After the addition was complete, the reaction mixture was stirred at rt for 30 minutes. A white precipitate formed which was collected by filtration and washed with water. The title compound was obtained after drying in vacuo (436 mg, 89%): 1H NMR (400 MHz, DMSO-d6) δ 7.37 (broad s, 1H), 7.14 (d, 2H, and broad s, 1H), 7.02 (d, 2H), 6.43 (s, 1H), 5.28 (s, 2H), 2.27 (s, 3H), 2.19 (s, 3H); ES-MS m/z 230 (MH)+; HPLC RT (Method E) 1.39 min.

Workup

  1. customall volatiles were removed in vacuo
  2. customThe crude acid chloride thus obtained
  3. additionAfter the addition
  4. stirringthe reaction mixture was stirred at rt for 30 minutes
  5. customA white precipitate formed which
  6. filtrationwas collected by filtration
  7. washwashed with water

Sources & evidence

ORD record
ord-e0ec9b153a0c424ab0660989703d2969
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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