Ethyl Acetate → HCID 90933494, compound

HRID 1854448Notes

Reaction equation

HRID 1854448 reaction equation
[C:1]([O:5][C:6](=[O:38])[NH:7][CH:8]1[CH2:12][CH:11]([C:13]([NH:15][NH:16][C:17]2[N:18]=[C:19]3[CH:25]=[CH:24][N:23]([S:26]([C:29]4[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=4)(=[O:28])=[O:27])[C:20]3=[N:21][CH:22]=2)=O)[CH:10]([CH2:36][CH3:37])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].O1CCOCC1.O=S(Cl)Cl.CCOC(C)=O>O>[CH2:36]([C@H:10]1[C@@H:11]([C:13]2[N:18]3[C:19]4[CH:25]=[CH:24][N:23]([S:26]([C:29]5[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=5)(=[O:28])=[O:27])[C:20]=4[N:21]=[CH:22][C:17]3=[N:16][N:15]=2)[CH2:12][C@@H:8]([NH:7][C:6](=[O:38])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH2:9]1)[CH3:37]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24386Thionyl ChlorideHCID 312751,4-DioxaneHCID 58010071HCID 58010071, compound

Product 1

HCID 90933494HCID 90933494, compoundYield 71.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A round-bottomed flask was charged with tert-butyl-3-ethyl-4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate (2.45 g, 4.55 mmol) and 1,4-dioxane (24 mL) to give a brown solution. TEA (2.54 mL, 18.2 mmol) was added followed by the addition of SOCl2 (0.50 mL, 6.8 mmol). The reaction mixture was heated at about 80° C. for about 5 h. The mixture was cooled to ambient temperature and EtOAc (100 mL) and water (30 mL) were added. The layers were partitioned and the organic layer was washed with water (2×30 mL) and brine (2×30 mL), dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure to give a brown residue. The crude material was purified by silica gel chromatography eluting with a gradient of 0-10% MeOH/DCM. The product-containing fractions were combined and concentrated to give tert-butyl (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamate (1.7 g, 71%): LC/MS (Table 2, Method a) Rt=2.50 min; MS m/z: 525 (M+H)+.

Workup

  1. customto give a brown solution
  2. temperatureThe mixture was cooled to ambient temperature
  3. customThe layers were partitioned
  4. washthe organic layer was washed with water (2×30 mL) and brine (2×30 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customto give a brown residue
  9. customThe crude material was purified by silica gel chromatography
  10. washeluting with a gradient of 0-10% MeOH/DCM
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-72186035fd694c7bbd50758624085fe2
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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