1,8-Diazabicyclo(5.4.0)undec-7-ene → Ethyl 2-(7-bromo-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl)acetate

HRID 1056063Notes

Reaction equation

HRID 1056063 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:7]([NH:9][CH2:10]/[CH:11]=[CH:12]/[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[O:8])[NH:5][CH:6]=1.C1CCN2C(=NCCC2)CC1>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:7](=[O:8])[NH:9][CH2:10][CH:11]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:5]2[CH:6]=1

Participants

4

Reactant 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 89793656(E)-ethyl 4-(4-bromo-1H-pyrrole-2-carboxamido)but-2-enoate

Product 1

HCID 89782100Ethyl 2-(7-bromo-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl)acetateYield 52.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(E)-Ethyl 4-(4-bromo-1H-pyrrole-2-carboxamido)but-2-enoate (2.35 g, 7.80 mmol) was treated with ACN (30 mL) and DBU (0.27 mL, 1.80 mmol) and stirred at RT for 2 h. The mixture was then concentrated in vacuo. Chromatographic purification of the residue (silica gel, 30-50% EtOAc in hexanes) afforded ethyl 2-(7-bromo-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl)acetate (1.24 g, 4.12 mmol, 52.8% yield) as a colorless viscous oil which crystallized to a white solid: 1H NMR (400 MHz, CDCl3) δ ppm 6.93 (1H, d, J=1.6 Hz), 6.84 (1H, d, J=1.8 Hz), 5.87 (1H, br. s.), 4.65 (1H, tt, J=6.8, 3.4 Hz), 4.11-4.24 (2H, m), 3.92 (1H, dd, J=12.8, 4.0 Hz), 3.46-3.54 (1H, m), 2.74-2.90 (2H, m), 1.26 (3H, t, J=7.1 Hz). m/z (ESI, +ve ion) 301.0/303.0 (M+H)+.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. customChromatographic purification of the residue (silica gel, 30-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8359824605d14b84b110bd638fdd7f52
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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