1-Butanol → ethyl 3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine-8-carboxylate

HRID 1969687Notes

Reaction equation

HRID 1969687 reaction equation
Cl[CH:2]([CH:8]=O)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[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].C(O)CCC>O1CCOCC1>[S:10]([N:20]1[C:28]2[N:27]=[CH:26][C:25]3[N:24]([C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[CH:8][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 2631-ButanolHCID 118030Ethyl (chloroformyl)acetate2×HCID 580099825-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-amine

Product 1

HCID 58557515ethyl 3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine-8-carboxylateYield 60%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

A solution of ethyl 2-chloro-3-oxopropanoate (1.60 g, 7.65 mmol, prepared as described in US2009005359A1) and 1,4-dioxane (10.0 mL) was added to 5-tosyl-5H-pyrrolo[3,2-b]pyrazin-2-amine (1.45 g, 5.03 mmol, Preparation #E.1.1) under nitrogen. Anhydrous butan-1-ol (30.0 mL) was added, a reflux condenser was attached, and the system was sealed. After about 30 min, the mixture was warmed to about 80° C. The solution was allowed to cool to ambient temperature. A solution of ethyl 2-chloro-3-oxopropanoate (2.78 g, 13.3 mmol) and 1,4-dioxane (5 mL) was added. After about 30 min, the reaction mixture was warmed to about 80° C. After about 30 min, the mixture was warmed to about 125° C. After about 48 h, the brown solution was allowed to cool to ambient temperature. The volatiles were removed under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 5-50% EtOAc in heptane to give ethyl 3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine-8-carboxylate (1.16 g, 60%): LC/MS (Table 1, Method b) Rt=2.52 min; MS m/z 385 (M+H)+.

Workup

  1. customa reflux condenser was attached
  2. customthe system was sealed
  3. temperatureto cool to ambient temperature
  4. waitAfter about 30 min
  5. temperaturethe reaction mixture was warmed to about 80° C
  6. waitAfter about 30 min
  7. temperaturethe mixture was warmed to about 125° C
  8. waitAfter about 48 h
  9. temperatureto cool to ambient temperature
  10. customThe volatiles were removed under reduced pressure
  11. customThe residue was purified by silica gel chromatography
  12. washeluting with a gradient of 5-50% EtOAc in heptane

Sources & evidence

ORD record
ord-9a3c0949a50c406ab1dbc7c9b7a0c678
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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