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

HRID 1969625Notes

Reaction equation

HRID 1969625 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

To (1S,4S,5R)-5-ethyl-2-oxabicyclo[2.2.1]heptan-3-one (0.835 g, 5.96 mmol, Preparation #GG.1) in 1,4-dioxane (12 mL) was added 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (Example #1, Step D, 1.81 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. Aqueous HCl (1 N, 50 mL) was added dropwise and the reaction mixture was stirred for about 30 min. The layers were separated. 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 concd 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)cyclopentane-carbohydrazide (1.887 g, 53%): LC/MS (Table 1, Method b) Rt=2.05 min; MS m/z: 444 (M+H)+.

Workup

  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

Sources & evidence

ORD record
ord-8001bde7cc3b4666a98f68f16eeeaf87
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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