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

HRID 2204489ノート

反応式

HRID 2204489 の反応式
[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].O=S(Cl)Cl.CCOC(C)=O.O>O1CCOCC1>[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]

参加物

6

反応物 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 24386Thionyl ChlorideHCID 58009789tert-butyl (1S,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate

生成物 1

HCID 58009863tert-Butyl-(1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1, 2, 4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamate収率 85.1%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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, Preparation #A.1) 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 and water (200 mL each) were added, and the layers were separated. The aqueous solution was extracted with EtOAc (2×100 mL) and the combined organic layers were washed with saturated aqueous NaHCO3 and brine (100 mL each). The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated 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 2, Method a) Rt=2.37 min; MS m/z: 497 (M+H)+.

後処理

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

出典と根拠

ORDレコード
ord-abc1f11095404a69b50fb371e8ee601f
出典データセット
uspto-grants-2016_06
特許番号
US09365579B2

反応ノート

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