Methyl acetoacetate → Methyl 4-(2-Chloro-4-fluorophenyl)-6-methyl-2-(2-thiazolyl)-1,4-dihydropyrimidine-5-carboxylate

HRID 1778457Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1778457
[ClH:1].[S:2]1[CH:6]=[CH:5][N:4]=[C:3]1[C:7]([NH2:9])=[NH:8].[C:10]([O:16][CH3:17])(=[O:15])[CH2:11][C:12]([CH3:14])=O.Cl[C:19]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:20]=1C=O.[C:28]([O-])(=O)C.[K+]>C(CO)(F)(F)F>[CH3:17][O:16][C:10]([C:11]1[CH:28]([C:19]2[CH:20]=[CH:23][C:24]([F:27])=[CH:25][C:26]=2[Cl:1])[N:8]=[C:7]([C:3]2[S:2][CH:6]=[CH:5][N:4]=2)[NH:9][C:12]=1[CH3:14])=[O:15]

Komponenten

6

Edukt 4

HCID 7757Methyl acetoacetateHCID 517044Potassium AcetateHCID 27791842-Chloro-5-FluorobenzaldehydeHCID 186795841,3-Thiazole-2-carboximidamide hydrochloride

Produkt 1

HCID 9820500Methyl 4-(2-Chloro-4-fluorophenyl)-6-methyl-2-(2-thiazolyl)-1,4-dihydropyrimidine-5-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 64092,2,2-TrifluoroethanolLösungsmittel

Versuchsvorschrift

To a stirred solution of thiazole-2-carboxamidine hydrochloride (0.13 g, 1.0 mmol), methyl acetoacetate (0.12 g, 1.0 mmol) and 2-chloro-5-fluorobenzaldehyde (0.16 g, 1.0 mmol) in CF3CH2OH (8 mL) was added potassium acetate (0.20 g, 2.0 mmol). The reaction mixture was refluxed for 16 hours. After it was cooled to room temperature, the reaction mixture was concentrated and the residue was dissolved in ethyl acetate and then washed with brine. The organic layer was dried over sodium sulfate. The solvent was concentrated, and the residue was purified by column chromatography (ethyl acetate/petroleum ether is from ¼ to ½) to afford 4-(2-chloro-4-fluoro-phenyl)-6-methyl-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester (Compound B) as a yellow solid. MS: calc'd (MH+) 366, measured (MH+) 366. 1H NMR (DMSO-d6, 400 MHz): δ ppm 9.98 (s, 1H), 7.97 (d, J=4.0 Hz, 1H), 7.90 (d, J=4.0 Hz, 1H), 7.41 (dd, J=8.0, 4.0 Hz, 1H), 7.35 (dd, J=8.0, 8.0 Hz, 1H), 7.18 (td, J=8.0, 4.0 Hz, 1H), 5.98 (s, 1H), 3.53 (s, 3H), 2.47 (s, 3H).

Aufarbeitung

  1. temperatureThe reaction mixture was refluxed for 16 hours
  2. concentrationthe reaction mixture was concentrated
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washwashed with brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationThe solvent was concentrated
  7. customthe residue was purified by column chromatography (ethyl acetate/petroleum ether is from ¼ to ½)

Quellen und Nachweise

ORD-Eintrag
ord-b8728a6a8efa446fbbef6fd22e5bc5bc
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09266904B2

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