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

HRID 1778457ノート

反応式

HRID 1778457 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 64092,2,2-Trifluoroethanol溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-b8728a6a8efa446fbbef6fd22e5bc5bc
出典データセット
uspto-grants-2016_02
特許番号
US09266904B2

反応ノート

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