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

HRID 63671노트

반응식

HRID 63671 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 64092,2,2-Trifluoroethanol용매

반응 조건

온도
150 °C

실험 절차

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 either refluxed for 16 hrs or heated at 150° C. in microwave oven for 2 hours. After it was cooled to room temperature, the reaction mixture was concentrated and the residue was dissolved in ethyl acetate and washed with brine. The organic layer was dried over sodium sulfate and 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): 6 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).

후처리

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

출처 및 근거

ORD 기록
ord-d689ecfabf7946178a6210f40f3aa2dd
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447086B2

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