Dibutyl sulfide → 4-(7-Methyl-1H-indazol-5-yl)-3-pyridin-2-yl-butyric acid tert-butyl ester

HRID 2099737노트

반응식

HRID 2099737 반응식
C(SCCCC)CCC.[N:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[Li].[C:17]([O:21][C:22](=[O:36])[CH:23]=[CH:24][CH2:25][C:26]1[CH:27]=[C:28]2[C:32](=[C:33]([CH3:35])[CH:34]=1)[NH:31][N:30]=[CH:29]2)([CH3:20])([CH3:19])[CH3:18]>CCOCC>[C:17]([O:21][C:22](=[O:36])[CH2:23][CH:24]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][N:10]=1)[CH2:25][C:26]1[CH:27]=[C:28]2[C:32](=[C:33]([CH3:35])[CH:34]=1)[NH:31][N:30]=[CH:29]2)([CH3:19])([CH3:20])[CH3:18]

참가 물질

5

반응물 3

HCID 11002Dibutyl sulfideHCID 690719374-(7-methyl-1H-indazol-5-yl)-but-2-enoic Acid Tert-Butyl EsterHCID 178506720HCID 178506720, 화합물

생성물 1

HCID 577945784-(7-Methyl-1H-indazol-5-yl)-3-pyridin-2-yl-butyric acid tert-butyl ester

시약·촉매·용매 1

HCID 3283Diethyl Ether용매2회

반응 조건

온도
0 °C

실험 절차

To a 50-mL oven-dried flask was added di-n-butylsulfide (261 mg, 1.781 mmol, 6.4 equiv) and cuprous iodide (170 mg, 0.891 mmol, 3.2 equiv) under nitrogen. Anhydrous ether (1 mL) was added and the suspension was cooled to 0° C. before the solution of 2-pyridinyl lithium was added via canuula. A yellowish brown precipitate was formed. After stirring at 0° C. for 15 min, the cooling bath was removed and 4-(7-methyl-1H-indazol-5-yl)-but-2-enoic acid tert-butyl ester (75.8 mg, 0.278 mmol, 1.0 equiv) in anhydrous ether (1 mL) was added via syringe. The dark solution was stirred at room temperature for 40 min. LCMS indicated the formation of the desired product. The reaction mixture was then partitioned between an aqueous ammonium hydroxide/ammonium chloride solution and ethyl acetate (upon shaking, the solids gradually dissolved to a blue aqueous solution). The layers were separated and the organic layer was washed with water, brine, dried over sodium sulfate and concentrated in vacuo to an oil. Careful flash column chromatography (5% methanol in methylene chloride) afforded the desired product (10.4 mg, 11%) which was carried on without farther purification. MS (ESI) 352 (M H)+, 296 (M-tBu)+.

후처리

  1. customTo a 50-mL oven-dried flask
  2. additionwas added via canuula
  3. customA yellowish brown precipitate was formed
  4. customthe cooling bath was removed
  5. stirringThe dark solution was stirred at room temperature for 40 min

출처 및 근거

ORD 기록
ord-38f34a022bf0434c8fdb08ec132e054a
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07569578B2

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