Acetonitrile → 7-Bromo-1-(2-chloro-3,6-difluorobenzyl)-8-methyl-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine

HRID 80559Notes

Reaction equation

HRID 80559 reaction equation
C[C:2]1[C:3]([Br:12])=[CH:4][C:5]2[NH:10][CH2:9][CH2:8][NH:7][C:6]=2[N:11]=1.[Cl:13][C:14]1[C:21]([F:22])=[CH:20][CH:19]=[C:18]([F:23])[C:15]=1[CH2:16]Br.[C:24](#N)C>C(Cl)Cl>[Br:12][C:3]1[CH:2]=[N:11][C:6]2[NH:7][CH2:8][CH2:9][N:10]([CH2:16][C:15]3[C:18]([F:23])=[CH:19][CH:20]=[C:21]([F:22])[C:14]=3[Cl:13])[C:5]=2[C:4]=1[CH3:24]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 27735492-(Bromomethyl)-3-chloro-1,4-difluorobenzeneHCID 670082847-Bromo-6-methyl-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine

Product 1

HCID 670070637-Bromo-1-(2-chloro-3,6-difluorobenzyl)-8-methyl-1,2,3,4-tetrahydropyrido[2,3-b]pyrazineYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1,2,3,4-Tetrahydro-6-methyl-7-bromo pyrido[2,3-b]pyrazine (0.15 g, 1 mmol), 2-chloro 3,6-difluoro-benzyl bromide (0.16 g, 1.05 mmol), KI (0.016 mmol, 0.01 g) in acetonitrile was subjected to microwave irradiation at 130° C. for 20 min. The solvent was stripped off and the crude residue was re-dissolved in CH2Cl2, washed with aqueous NaHCO3 solution. Upon drying, the residue was chromatographed, eluting with a mixture of hexanes-EtOAc (7:3) to furnish pure desired product (0.086 g 23%). The undesired N-alkylation product was also obtained and the structural differentiation was based on NOE NMR experiment.

Workup

  1. customirradiation at 130° C. for 20 min
  2. washwashed with aqueous NaHCO3 solution
  3. customUpon drying
  4. customthe residue was chromatographed
  5. washeluting with a mixture of hexanes-EtOAc (7:3)

Sources & evidence

ORD record
ord-ffbba0e817914055b0f8675d72219413
Source dataset
uspto-grants-2014_09
Patent number
US08846664B2

Reaction notes

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