Ethyl 2-chloroacetoacetate → HCID 87190583, compound

HRID 604887Notes

Reaction equation

HRID 604887 reaction equation
Cl[CH:2]([C:8]([CH3:10])=O)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:11]([S-:13])#[N:12].[K+].[CH3:15][O:16][C:17]1[CH:18]=[C:19]([NH2:29])[CH:20]=[CH:21][C:22]=1[N:23]1[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24]1>C(O)C>[CH2:6]([O:5][C:3]([C:2]1[S:13][C:11]([NH:29][C:19]2[CH:20]=[CH:21][C:22]([N:23]3[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24]3)=[C:17]([O:16][CH3:15])[CH:18]=2)=[N:12][C:8]=1[CH3:10])=[O:4])[CH3:7]

Participants

5

Reactant 3

HCID 11858Ethyl 2-chloroacetoacetateHCID 516872Potassium thiocyanateHCID 454801813-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline

Product 1

HCID 87190583HCID 87190583, compoundYield 17.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 46 mg (0.25 mmol) ethyl 2-chloroacetoacetate and of 36 mg (0.375 mmol) potassium rhodanide in ethanol (0.75 ml) was stirred at room temperature for 1 hour. 51 mg (0.25 mmol) 3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamine was added and the reaction was heated to reflux for 3 hours. A solid precipitated. The reaction was diluted with water and extracted twice with ethyl acetate. The insoluble precipitate was filtered off, washed with ethyl acetate and dried to yield the 16.5 mg of the title compound. The organic layer was dried over sodium sulphate, filtered and the solvent was evaporated in vacuo. The residue was purified on silica gel with methylene chloride/methanol 19/1. The fraction with the product was stirred with diethyl ether at room temperature and the solid was filtered off. The product was combined yielding 32 mg (35%) 2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-4-methyl-thiazole-5-carboxylic acid ethyl ester as a yellow solid. MS ISP (m/e): 373.2 (100) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm)=10.93 (s, 1H), 8.49 (s, 1H), 7.61 (s, 1H), 7.43 (d, 1H), 7.37 (s, 1H), 7.31 (s, 1H), 4.22 (q, 2H), 3.84 (s, 3H), 2.55 (s, 3H), 2.24 (s, 3H), 1.27 (t, 3H).

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 3 hours
  3. customA solid precipitated
  4. additionThe reaction was diluted with water
  5. extractionextracted twice with ethyl acetate
  6. filtrationThe insoluble precipitate was filtered off
  7. washwashed with ethyl acetate
  8. customdried

Sources & evidence

ORD record
ord-912f9dd378554031891b3e5604cb478f
Source dataset
uspto-grants-2011_03
Patent number
US07910740B2

Reaction notes

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