Hydrochloric Acid → (1S,2R,4S)-2-ethyl-4-hydroxy-N'-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbohydrazide

HRID 1969723ノート

反応式

HRID 1969723 の反応式
[CH2:1]([C@@H:3]1[CH2:8][C@H:7]2[CH2:9][C@@H:4]1[C:5](=[O:10])[O:6]2)[CH3:2].[NH:11]([C:13]1[N:14]=[C:15]2[CH:21]=[CH:20][N:19]([S:22]([C:25]3[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=3)(=[O:24])=[O:23])[C:16]2=[N:17][CH:18]=1)[NH2:12].C[Al](C)C.Cl>O1CCOCC1>[CH2:1]([C@@H:3]1[CH2:8][C@H:7]([OH:6])[CH2:9][C@@H:4]1[C:5]([NH:12][NH:11][C:13]1[N:14]=[C:15]2[CH:21]=[CH:20][N:19]([S:22]([C:25]3[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=3)(=[O:24])=[O:23])[C:16]2=[N:17][CH:18]=1)=[O:10])[CH3:2]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 16682925TrimethylaluminumHCID 580098102-Hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazineHCID 67998117(1S,4S,5R)-5-ethyl-2-oxabicyclo[2.2.1]heptan-3-one

生成物 1

HCID 58557121(1S,2R,4S)-2-ethyl-4-hydroxy-N'-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbohydrazide収率 71.4%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
80 °C

実験手順

To (1S,4S,5R)-5-ethyl-2-oxabicyclo[2.2.1]heptan-3-one (0.835 g, 5.96 mmol) in 1,4-dioxane (12 mL) was added 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (step D, 1.810 g, 5.96 mmol). The reaction mixture was heated at about 80° C. for about 16 h then cooled to ambient temperature. 1,4-Dioxane (25 mL) and trimethylaluminum (2 N in toluene, 9 mL, 18 mmol) were added sequentially. The reaction mixture was stirred at ambient temperature for about 30 min then HCl (1 N aqueous, 50 mL) was added dropwise and the reaction mixture was stirred for about 30 min. The layers were separated and the aqueous portion was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with water (10 mL), saturated aqueous NaHCO3 (15 mL), brine (15 mL) and dried over anhydrous MgSO4, filtered, and coned under reduced pressure. The residue was purified using silica gel chromatography (40 g) eluting with 100% EtOAc to give (1S,2R,4S)-2-ethyl-4-hydroxy-N′-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbohydrazide (1.887 g, 71%): LC/MS (Table 1, Method b) Rt=2.05 min; MS m/z: 444 (M+H)+.

後処理

  1. temperaturethen cooled to ambient temperature
  2. stirringthe reaction mixture was stirred for about 30 min
  3. customThe layers were separated
  4. extractionthe aqueous portion was extracted with EtOAc (2×100 mL)
  5. washThe combined organic extracts were washed with water (10 mL), saturated aqueous NaHCO3 (15 mL), brine (15 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customThe residue was purified
  9. washeluting with 100% EtOAc

出典と根拠

ORDレコード
ord-2cdc1bb1e0ae4338ba9434ea62d4bbfa
出典データセット
uspto-grants-2013_04
特許番号
US08426411B2

反応ノート

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