Methanol → 2-(3-chlorophenyl)-6-(trifluoromethyl)pyrimidin-4(3H)-one

HRID 1508907노트

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HRID 1508907 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](=[NH:7])[NH2:6].[F:11][C:12]([F:22])([F:21])[C:13](=O)[CH2:14][C:15](OCC)=[O:16].C[O-].[Na+].CO>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[NH:6][C:15](=[O:16])[CH:14]=[C:13]([C:12]([F:22])([F:21])[F:11])[N:7]=2)[CH:8]=[CH:9][CH:10]=1

참가 물질

6

반응물 4

HCID 887MethanolHCID 67793Ethyl 4,4,4-trifluoroacetoacetateHCID 2041443-Chloro-benzamidineHCID 10942334Sodium Methoxide

생성물 1

HCID 1362248182-(3-chlorophenyl)-6-(trifluoromethyl)pyrimidin-4(3H)-one수율 51.8%

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
0 °C

실험 절차

A 500-mL round bottomed flask was charged with 3-chlorobenzimidamide (4.81 g, 25.3 mmol), ethyl 4,4,4-trifluoro-3-oxobutanoate (5.00 g, 27.1 mmol), and ethanol (90 mL) and cooled to 0° C. A 25% sodium methoxide solution in methanol (13.0 mL, 55.3 mmol) was added to the mixture. The resulting mixture was stirred at reflux for 20 h. After this time, the mixture was cooled to room temperature and concentrated under reduced pressure to 25 mL. The residual slurry was cautiously treated with 2N HCl (50 mL) forming a solid. The solid was collected by filtration and washed with water followed by ether to afford the title compound (3.60 g, 48%) as a white solid, which was carried forward into the next step without further purification. MW=274.63. 1H NMR (DMSO-d6, 500 MHz) δ 13.39 (s, 1H), 8.18 (s, 1H), 8.10 (d, J=7.5 Hz, 1H), 7.73-7.69 (m, 1H), 7.60 (t, J=8.0 Hz, 1H), 6.94 (s, 1H).

후처리

  1. temperatureat reflux for 20 h
  2. temperatureAfter this time, the mixture was cooled to room temperature
  3. concentrationconcentrated under reduced pressure to 25 mL
  4. additionThe residual slurry was cautiously treated with 2N HCl (50 mL)
  5. customforming a solid
  6. filtrationThe solid was collected by filtration
  7. washwashed with water

출처 및 근거

ORD 기록
ord-8d6573d9cedf45149ba4e3cd1e79c8a7
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221843B2

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