Acetic Acid → 6-Bromo-1H-pyrazolo[4,3-b]pyridine

HRID 711053노트

반응식

HRID 711053 반응식
[Br:1][C:2]1[CH:3]=[C:4]([NH:9]C(=O)C)[C:5]([CH3:8])=[N:6][CH:7]=1.C([O-])(=O)C.[K+].C(O)(=O)C.C(OC(=O)C)(=O)C.C(O[N:35]=O)CC(C)C.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[NH:9][N:35]=[CH:8][C:5]2=[N:6][CH:7]=1

참가 물질

8

반응물 6

HCID 176Acetic AcidHCID 7918Acetic AnhydrideHCID 8053Isoamyl NitriteHCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 67151326N-(5-bromo-2-methylpyridin-3-yl)acetamide

생성물 1

HCID 401522596-Bromo-1H-pyrazolo[4,3-b]pyridine수율 77%

시약·촉매·용매 1

HCID 6212Chloroform용매

실험 절차

To a solution of N-(5-bromo-2-methylpyridin-3-yl)acetamide (8.28 g, 36 mmol) in chloroform (550 mL) at ambient temperature was added potassium acetate (4.32 g, 43.6 mmol), acetic acid (2.5 mL, 43.6 mmol) and followed by acetic anhydride (6.86 mL, 72.6 mmol). The mixture was stirred at ambient temperature for 15 minutes before being heated to 40° C. Isoamylnitrite was then added dropwise. The reaction was then stirred at 60° C. for 48 hours. The reaction mixture was poured slowly into a saturated solution of sodium bicarbonate (500 mL) at 0° C. The organic phase was retained and the aqueous phase extracted with dichloromethane (500 mL). The combined organics were then concentrated to a brown oil which was dissolved in methanol (500 mL). Aqueous sodium hydroxide (2 M, 500 mL) was added at 0° C. and the mixture stirred at ambient temperature for 1 hour before the methanol was removed in vacuo. The aqueous mixture was then extracted with ethyl acetate (3×500 mL). The combined organics were dried over magnesium sulfate, filtered, and the solvent removed in vacuo to give 6-bromo-1H-pyrazolo[4,3-b]pyridine as a light brown solid (5.5 g, 77%). 1HNMR (400 MHz, CD3OD, δ): 8.55 (s, 1H), 8.24 (s, 1H), 8.21 (s, 1H).

후처리

  1. temperaturebefore being heated to 40° C
  2. stirringThe reaction was then stirred at 60° C. for 48 hours
  3. extractionthe aqueous phase extracted with dichloromethane (500 mL)
  4. concentrationThe combined organics were then concentrated to a brown oil which
  5. dissolutionwas dissolved in methanol (500 mL)
  6. additionAqueous sodium hydroxide (2 M, 500 mL) was added at 0° C.
  7. stirringthe mixture stirred at ambient temperature for 1 hour before the methanol
  8. customwas removed in vacuo
  9. extractionThe aqueous mixture was then extracted with ethyl acetate (3×500 mL)
  10. dry with materialThe combined organics were dried over magnesium sulfate
  11. filtrationfiltered
  12. customthe solvent removed in vacuo

출처 및 근거

ORD 기록
ord-215536a5d9214ddeac50f83494cc310e
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181252B2

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