Pyridine → 2-(Trimethylacetamido)-4-(3-trifluoromethylphenylcarbamoylmethyl)thiazole

HRID 1112042

Reaction equation

HRID 1112042 reaction equation
Br[CH2:2][C:3](=O)[CH2:4][C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=1)=[O:6].N1C=CC=CC=1.[CH3:25][C:26]([CH3:34])([CH3:33])[C:27]([NH:29][C:30]([NH2:32])=[S:31])=[O:28]>O.C(O)C>[CH3:25][C:26]([CH3:34])([CH3:33])[C:27]([NH:29][C:30]1[S:31][CH:2]=[C:3]([CH2:4][C:5](=[O:6])[NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[N:32]=1)=[O:28]

Participants

6

Reactant 3

HCID 1049PyridineHCID 18948826N-trimethylacetylthioureaHCID 223476964-Bromo-3'-trifluoromethylacetoacetanilide

Product 1

HCID 273974612-(Trimethylacetamido)-4-(3-trifluoromethylphenylcarbamoylmethyl)thiazoleYield 88%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

A 500 ml reaction flask fitted with a magnetic stirrer, heating mantle, thermometer and water-cooled condenser was charged with 44.7 g (0.138 mole) of 4-bromo-3'-trifluoromethylacetoacetanilide, 350 ml of absolute ethanol and 15 g (0.19 mole) of pyridine. A 26 g sample (0.162 mole) of N-trimethylacetylthiourea [m.p. 140°-42°; prepared as described by Moore and Crossley in The Journal of the American Chemical Society, vol. 62, p. 3273 (1940)] was added to the reaction solution. As the substituted thiourea dissolved, the reaction temperature increased from 24° to 31°. The solution was refluxed for four hours and poured into 1.5 liters of water. With stirring, the residual oil crystallized. The product was collected and washed with water. There was obtained 46.8 g (88%) of white solid, m.p. 147°-52°. One recrystallization from ethyl acetate-heptane yielded material which melted at 153°-55°. N.M.R. (dimethyl-d6 sulfoxide) ∂ 1.3 (tert-butyl), 3.8 (CH2), 6.9 (hetero-aromatic), 7.3-8.1 (aromatic).

Workup

  1. customA 500 ml reaction flask
  2. customfitted with a magnetic stirrer
  3. temperatureheating mantle
  4. customprepared
  5. addition3273 (1940)] was added to the reaction solution
  6. temperaturethe reaction temperature increased from 24° to 31°
  7. temperatureThe solution was refluxed for four hours
  8. customthe residual oil crystallized
  9. customThe product was collected
  10. washwashed with water

Sources & evidence

ORD record
ord-d576248325b9445ab979f780d0723c86
Source dataset
uspto-grants-1978_10
Patent number
US04120690

Linked notes

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