Acetyl chloride → N-(4-(2-amino-2-methylpropoxy)-3-(4-chloro-2-methyl-2H-pyrazol-3-yl)phenyl)-3-(trifluoromethyl)benzamide

HRID 1685960Notes

Reaction equation

HRID 1685960 reaction equation
C(Cl)(=O)C.[N+:5]([C:8]([CH3:38])([CH3:37])[CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:29])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)=[CH:13][C:12]=1[C:30]1[N:31]([CH3:36])[N:32]=[CH:33][C:34]=1[Cl:35])([O-])=O>CO.[Zn]>[NH2:5][C:8]([CH3:38])([CH3:37])[CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:29])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:26])[F:27])[CH:20]=2)=[CH:13][C:12]=1[C:30]1[N:31]([CH3:36])[N:32]=[CH:33][C:34]=1[Cl:35]

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 67265611HCID 67265611, compound

Product 1

HCID 57814739N-(4-(2-amino-2-methylpropoxy)-3-(4-chloro-2-methyl-2H-pyrazol-3-yl)phenyl)-3-(trifluoromethyl)benzamideYield 89.8%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Conditions

Temperature
23 °C

Procedure

Acetyl chloride (97 μl, 1.4 mmol) was added dropwise to a solution of N-(4-(2-nitro-2-methylpropoxy)-3-(4-chloro-2-methyl-2H-pyrazol-3-yl)phenyl)-3-(trifluoromethyl)benzamide (68 mg, 0.136 mmol) in MeOH (2.0 mL). Zinc dust (89 mg, 1.4 mmol) was added, and the mixture was stirred at 23° C. After 1 hr, the mixture was filtered and the filtrate was evaporated to dryness. The residue was taken up in ammonium hydroxide (35%), diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried with sodium sulfate, filtered, and evaporated to dryness. The crude product was dissolved in methanol, a solution of acetyl chloride (15 μl) in methanol was added, and the solution was evaporated to dryness. The residue was dissolved in water—acetonitrile 1:1 and lyophilized to afford the product (57 mg, 83%) as the hydrochloride. LCMS m/z (%)=469.4 (M+H 37Cl 58.9%), 467.4 (M+H 35Cl 83.7%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.19 (s, 3 H), 1.20 (s, 3 H), 3.66 (s, 3 H), 3.87 (d, J=9.60 Hz, 1 H), 4.02 (d, J=9.85 Hz, 1 H), 7.31 (d, J=9.09 Hz, 1 H), 7.67 (s, 1 H), 7.72 (d, J=2.53 Hz, 1 H), 7.80 (t, J=7.71 Hz, 1 H), 7.92-8.08 (m, 5 H), 8.27 (d, J=8.08 Hz, 1H), 8.30 (s, 1 H), 10.58 (s, 1 H).

Workup

  1. filtrationthe mixture was filtered
  2. customthe filtrate was evaporated to dryness
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness
  9. dissolutionThe crude product was dissolved in methanol
  10. additiona solution of acetyl chloride (15 μl) in methanol was added
  11. customthe solution was evaporated to dryness
  12. dissolutionThe residue was dissolved in water—acetonitrile 1:1

Sources & evidence

ORD record
ord-8698fcc7975d4a58a56ae386c22aa93f
Source dataset
uspto-grants-2012_04
Patent number
US08148417B2

Reaction notes

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