Methyl N-{5-bromo-3-[(2-chloro-3,6-difluorobenzyl)amino]pyrazin-2-yl}-beta-alaninate → 3-bromo-5-(2-chloro-3,6-difluorobenzyl)-5,7,8,9-tetrahydro-6H-pyrazino[2,3-b][1,4]diazepin-6-one

HRID 80564Notes

Reaction equation

HRID 80564 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([NH:15][CH2:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[C:19]([F:24])[C:18]=2[Cl:25])[C:5]([NH:8][CH2:9][CH2:10][C:11](OC)=[O:12])=[N:6][CH:7]=1>CC(O)=O>[Br:1][C:2]1[CH:7]=[N:6][C:5]2[NH:8][CH2:9][CH2:10][C:11](=[O:12])[N:15]([CH2:16][C:17]3[C:22]([F:23])=[CH:21][CH:20]=[C:19]([F:24])[C:18]=3[Cl:25])[C:4]=2[N:3]=1

Participants

3

Reactant 1

HCID 86659427Methyl N-{5-bromo-3-[(2-chloro-3,6-difluorobenzyl)amino]pyrazin-2-yl}-beta-alaninate

Product 1

HCID 866594293-bromo-5-(2-chloro-3,6-difluorobenzyl)-5,7,8,9-tetrahydro-6H-pyrazino[2,3-b][1,4]diazepin-6-one

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of methyl N-{5-bromo-3-[(2-chloro-3,6-difluorobenzyl)amino]pyrazin-2-yl}-β-alaninate in HOAc was heated at reflux for 4 hrs. After volatile components were removed on rotavap, the residue was taken in to a mixture of EtOAc and aq. NaHCO3. The combined organic layers from extraction was dried, concentrated, and then purified by silica gel column chromatography (EtOAc/Hexanes 4:1) to furnish 3-bromo-5-(2-chloro-3,6-difluorobenzyl)-5,7,8,9-tetrahydro-6H-pyrazino[2,3-b][1,4]diazepin-6-one.

Workup

  1. temperatureat reflux for 4 hrs
  2. customAfter volatile components were removed on rotavap
  3. additionthe residue was taken in to a mixture of EtOAc and aq. NaHCO3
  4. extractionThe combined organic layers from extraction
  5. customwas dried
  6. concentrationconcentrated
  7. custompurified by silica gel column chromatography (EtOAc/Hexanes 4:1)

Sources & evidence

ORD record
ord-804ef3f1b16e432d861abd94f5563870
Source dataset
uspto-grants-2014_09
Patent number
US08846664B2

Reaction notes

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