Ethyl 2-chloro-3-(2-chlorophenyl)-3-oxopropanoate → Ethyl 2-[2-(acetylamino)pyridin-4-yl]-4-(2-chlorophenyl)-1,3-thiazole-5-carboxylate

HRID 2282311Notes

Reaction equation

HRID 2282311 reaction equation
Cl[CH:2]([C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:16])=O)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[NH2:17][C:18]([C:20]1[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=1)=[S:19]>C(O)(C)C>[C:27]([NH:26][C:22]1[CH:21]=[C:20]([C:18]2[S:19][C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[C:8]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:16])[N:17]=2)[CH:25]=[CH:24][N:23]=1)(=[O:29])[CH3:28]

Participants

4

Reactant 2

HCID 13593390Ethyl 2-chloro-3-(2-chlorophenyl)-3-oxopropanoateHCID 58095134N-(4-carbamothioylpyridin-2-yl)acetamide

Product 1

HCID 58095112Ethyl 2-[2-(acetylamino)pyridin-4-yl]-4-(2-chlorophenyl)-1,3-thiazole-5-carboxylateYield 21.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
94 °C

Procedure

To a stirred solution of crude ethyl 2-chloro-3-(2-chlorophenyl)-3-oxopropanoate (1.390 g, 5.320 mmol) in absolute isopropyl alcohol (50.00 mL) was added N-[4-(aminocarbonothioyl)pyridin-2-yl]acetamide (1.140 g, 5.860 mmol) and the resulting solution was fitted with a condenser and stirred for 23 h at 94° C. The mixture was cooled to ambient temperature and half the solvent was removed in vacuo. Diethyl ether (30.0 mL) was added to allow the formation of the thioamide by-product. The by-product was separated by filtration and the solvent was removed in vacuo. The residue was purified by column chromatography (SiO2, elution with 0-100% EtOAc in hexanes) to provide 0.457 g of product as a yellow oil (21% 2 steps). LC/MS (AA) ES+ 402. NMR (400 MHz, d1 CDCl3) δ: 8.77 (br s, 1H), 8.37-8.35 (m, 1H), 7.71-7.70 (m, 1H), 7.50-7.46 (m, 2H), 7.41-7.46 (m, 3H), 4.24 (q, J=7.2 Hz, 2H), 2.24 (s, 3H), 1.26 (t, J=7.2 Hz, 3H).

Workup

  1. customthe resulting solution was fitted with a condenser
  2. temperatureThe mixture was cooled to ambient temperature
  3. customhalf the solvent was removed in vacuo
  4. additionDiethyl ether (30.0 mL) was added
  5. customThe by-product was separated by filtration
  6. customthe solvent was removed in vacuo
  7. customThe residue was purified by column chromatography (SiO2, elution with 0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-3890e4b6adb1489a94d69c119a2baa0f
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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