Ethyl Acetate → tert-Butyl-(1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1, 2, 4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamate

HRID 1969590노트

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HRID 1969590 반응식
[S:1]([N:11]1[C:15]2=[N:16][CH:17]=[C:18]([NH:20][NH:21][C:22]([C@@H:24]3[CH2:28][CH2:27][C@H:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:25]3)=O)[N:19]=[C:14]2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].C1(C(O)=O)CCCC1.O=S(Cl)Cl.CCOC(C)=O>O1CCOCC1.O>[C:32]([O:31][C:30](=[O:36])[NH:29][C@H:26]1[CH2:27][CH2:28][C@@H:24]([C:22]2[N:19]3[C:14]4[CH:13]=[CH:12][N:11]([S:1]([C:4]5[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=5)(=[O:2])=[O:3])[C:15]=4[N:16]=[CH:17][C:18]3=[N:20][N:21]=2)[CH2:25]1)([CH3:34])([CH3:35])[CH3:33]

참가 물질

7

반응물 4

HCID 8857Ethyl AcetateHCID 18840Cyclopentanecarboxylic acidHCID 24386Thionyl ChlorideHCID 58009789tert-butyl (1S,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate

생성물 1

HCID 58009863tert-Butyl-(1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1, 2, 4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamate수율 85%

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

To a solution of tert-butyl (1S,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate (9.30 g, 18.1 mmol, prepared using A from Example #1 Step D, and (1R,3S)-3-tert-butoxycarbonylamino)cyclopentanecarboxylic acid [Peptech]) in 1,4-dioxane (100 mL) was added TEA (10.0 mL, 72.3 mmol) and SOCl2 (2.11 mL, 28.9 mmol). The mixture was heated at about 80° C. for about 1.5 h. The reaction mixture was cooled to ambient temperature, EtOAc (200 mL) and water (200 mL) were added, and the layers were separated. The aqueous portion was extracted with EtOAc (2×100 mL) and the combined organic extracts were washed with saturated aqueous NaHCO3 (100 mL) and brine (100 mL), dried over anhydrous Na2SO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 25-100% EtOAc in DCM to give tert-butyl-(1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamate (7.65 g, 85%): LC/MS (Table 1, Method a) Rt=2.37 min; MS m/z: 497 (M+H)+.

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe layers were separated
  3. extractionThe aqueous portion was extracted with EtOAc (2×100 mL)
  4. washthe combined organic extracts were washed with saturated aqueous NaHCO3 (100 mL) and brine (100 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customThe crude material was purified by silica gel chromatography
  8. washeluting with a gradient of 25-100% EtOAc in DCM

출처 및 근거

ORD 기록
ord-1bc2d11156a14d25a87441242a3e1b35
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426411B2

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