Methyl Nicotinate → HCID 178420143, 화합물

HRID 42310

반응식

HRID 42310 반응식
[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13](=O)[CH3:14])=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:16](OC)(=O)[C:17]1[CH:22]=[CH:21][CH:20]=[N:19][CH:18]=1.CC(C)([O-])C.[K+].[H-].[Na+].O.[NH2:35][NH2:36]>O1CCCC1.[Cl-].[NH4+].[Cl-].[Na+].C(O)(=O)C.C(=O)(O)[O-].[Na+]>[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[NH:36][N:35]=[C:16]([C:17]4[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=4)[CH:14]=3)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

참가 물질

11

반응물 5

HCID 7151Methyl Nicotinate2회HCID 24654Hydrazine hydrate (1:1)HCID 24758Sodium hydrideHCID 226310721-(2-Phenylpyrimidin-5-yl)ethanone2회HCID 23665647Potassium tert-butoxide

생성물 1

HCID 178420143HCID 178420143, 화합물

시약·촉매·용매 5

HCID 176Acetic Acid용매HCID 5234Sodium Chloride용매HCID 8028Tetrahydrofuran용매2회HCID 25517Ammonium Chloride용매HCID 516892Sodium Bicarbonate용매

반응 조건

온도
50 °C

실험 절차

To a solution consisting of 1-(2-phenylpyrimidin-5-yl)ethanone (Example 14, Step A, 46 mg, 0.23 mmol) and methyl nicotinate (35 mg, 0.25 mmol) in tetrahydrofuran (1 mL) was added a solution consisting of potassium tert-butoxide in tetrahydrofuran (0.28 mL, 0.28 mmol). The reaction mixture was stirred overnight. Analysis of the reaction mixture by TLC (1:3 ethyl acetate-hexanes) showed the 1-(2-phenylpyrimidin-5-yl)ethanone was not consumed. To the reaction mixture was added methyl nicotinate (118 mg, 0.86 mmol) and sodium hydride (10 mg, 0.23 mmol, 60% dispersion), and the reaction mixture was heated at 50° C. for one hour. The reaction mixture was diluted with a saturated aqueous solution of ammonium chloride and sodium chloride and the organic material was extracted three times with ethyl acetate. The combined organic phase was dried over magnesium sulfate, filtered and concentrated to dryness to provide a crude material. To a solution consisting of this crude material in acetic acid was added excess hydrazine hydrate and the reaction mixture was heated at 50° C. for two hours followed by 80° C. overnight. The reaction mixture was diluted with saturated aqueous sodium bicarbonate and the organic material was extracted three times with ethyl acetate. The combined organic phase was dried over magnesium sulfate, filtered, and concentrated to dryness. The crude material was chromatographed on silica (4 g) eluted with 1:4:5 v/v dichloromethane-ethyl acetate-hexane to 1:6:4 to afford the title compound (10 mg) as a tan solid; H-PGDS FPBA IC50: 1.3 μM.

후처리

  1. additionwas added a solution
  2. customwas not consumed
  3. extractionthe organic material was extracted three times with ethyl acetate
  4. dry with materialThe combined organic phase was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customto provide a crude material
  8. temperaturethe reaction mixture was heated at 50° C. for two hours
  9. waitfollowed by 80° C. overnight
  10. extractionthe organic material was extracted three times with ethyl acetate
  11. dry with materialThe combined organic phase was dried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated to dryness
  14. customThe crude material was chromatographed on silica (4 g)
  15. washeluted with 1:4:5 v/v dichloromethane-ethyl acetate-hexane to 1:6:4

출처 및 근거

ORD 기록
ord-0c98fe1714914c4fba15f8f28fd53980
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536185B2

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