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 1969590Notes

Reaction equation

HRID 1969590 reaction equation
[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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 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 (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)+.

Workup

  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

Sources & evidence

ORD record
ord-1bc2d11156a14d25a87441242a3e1b35
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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