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

HRID 2204491Notes

Reaction equation

HRID 2204491 reaction equation
S([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)(C1C=CC(C)=CC=1)(=O)=O.O=S(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+].O>O1CCOCC1.CCOC(C)=O>[C:22]1([C@@H:24]2[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]2)[N:19]2[C:14]3[CH:13]=[CH:12][NH:11][C:15]=3[N:16]=[CH:17][C:18]2=[N:20][N:21]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 24386Thionyl ChlorideHCID 58009789tert-butyl (1S,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate

Product 1

HCID 136198944tert-butyl (1S,3R)-3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamateYield 90.9%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl (1S,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate (4.73 g, 9.19 mmol, Preparation #A.1) in 1,4-dioxane (50 mL) was added TEA (5.10 mL, 36.8 mmol) and SOCl2 (1.34 mL, 18.4 mmol). The reaction mixture was heated at about 80° C. After about 1.5 h, saturated aqueous Na2CO3 (100 mL) was added and heating was resumed at about 80° C. for about 6 h. The reaction was cooled to ambient temperature for about 3 days and then heated at about 80° C. for about 16 h. Water and EtOAc (100 mL each) were added and the layers were separated. The aqueous layer was then extracted with additional EtOAc (2×100 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude solid was triturated with petroleum ether (b.p. 30-60° C.; 30 mL) and collected by vacuum filtration, while washing with additional petroleum ether (b.p. 30-60° C.; 20 mL), to give tert-butyl (1S,3R)-3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamate as a light brown solid (2.86 g, 86%): LC/MS (Table 2, Method a) Rt=1.75 min; MS m/z: 343 (M+H)+.

Workup

  1. temperatureheating
  2. waitwas resumed at about 80° C. for about 6 h
  3. temperatureThe reaction was cooled to ambient temperature for about 3 days
  4. temperatureheated at about 80° C. for about 16 h
  5. customthe layers were separated
  6. extractionThe aqueous layer was then extracted with additional EtOAc (2×100 mL)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude solid was triturated with petroleum ether (b.p. 30-60° C.; 30 mL)
  12. filtrationcollected by vacuum filtration
  13. washwhile washing with additional petroleum ether (b.p. 30-60° C.; 20 mL)

Sources & evidence

ORD record
ord-59ef5599db2842fa8f445fcbe97905bd
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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