1,4-Dioxane → ethyl 3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine-7-carboxylate

HRID 1969577Notes

Reaction equation

HRID 1969577 reaction equation
[CH2:1]([O:3][C:4](=[O:9])[C:5](=O)[CH2:6]Br)[CH3:2].[S:10]([N:20]1[C:28]2[C:23](=[N:24][C:25]([NH2:29])=[CH:26][N:27]=2)[CH:22]=[CH:21]1)([C:13]1[CH:19]=[CH:18][C:16]([CH3:17])=[CH:15][CH:14]=1)(=[O:12])=[O:11].O1CCOCC1>CC#N>[S:10]([N:20]1[C:28]2[N:27]=[CH:26][C:25]3[N:24]([CH:6]=[C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:9])[N:29]=3)[C:23]=2[CH:22]=[CH:21]1)([C:13]1[CH:14]=[CH:15][C:16]([CH3:17])=[CH:18][CH:19]=1)(=[O:11])=[O:12]

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 66144Ethyl bromopyruvateHCID 580099825-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-amine

Product 1

HCID 58557905ethyl 3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine-7-carboxylateYield 75.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-Bromo-2-oxo-propionic acid ethyl ester (0.090 mL, 0.72 mmol) was added to a mixture of 5-tosyl-5H-pyrrolo[3,2-b]pyrazin-2-amine (0.180 g, 0.624 mmol, prepared using E from Example #3 Step E and HCl) and 1,4-dioxane (3.5 mL) under nitrogen. After about 3 days, the volatiles were removed under reduced pressure. The residue was slurried in Et2O (5 mL) and then filtered to afford a tan powder. The solid was slurried in MeCN (3.50 mL) under nitrogen. PFPAA (0.40 mL, 2.1 mmol) was added. After about 30 min, the volatiles were removed under reduced pressure. The residue was dissolved in DCM (20 mL) and washed with saturated aqueous NaHCO3/water (2:1, 20 mL). The aqueous layer was extracted with DCM (20 mL). The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 20-100% EtOAc/heptane to afford ethyl 3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine-7-carboxylate (0.181 g, 75%): LC/MS (Table 1, Method n) Rt=0.70 min; MS m/z: 385 (M+H)+.

Workup

  1. customthe volatiles were removed under reduced pressure
  2. filtrationfiltered
  3. customto afford a tan powder
  4. additionPFPAA (0.40 mL, 2.1 mmol) was added
  5. waitAfter about 30 min
  6. customthe volatiles were removed under reduced pressure
  7. dissolutionThe residue was dissolved in DCM (20 mL)
  8. washwashed with saturated aqueous NaHCO3/water (2:1, 20 mL)
  9. extractionThe aqueous layer was extracted with DCM (20 mL)
  10. dry with materialThe combined organics were dried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by silica gel chromatography
  14. washeluting with a gradient of 20-100% EtOAc/heptane

Sources & evidence

ORD record
ord-ed34584311e2459180b2f4559a4b5fc5
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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