Dimethyl Sulfide → 7-Bromo-1-(2-chloro-3,6-difluorobenzyl)-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine

HRID 80538Notes

Reaction equation

HRID 80538 reaction equation
[Br:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:14][C:15]3[C:20]([F:21])=[CH:19][CH:18]=[C:17]([F:22])[C:16]=3[Cl:23])[C:9](=O)[C:10](=O)[NH:11][C:5]2=[N:4][CH:3]=1.S(C)C>C1COCC1>[Br:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:14][C:15]3[C:20]([F:21])=[CH:19][CH:18]=[C:17]([F:22])[C:16]=3[Cl:23])[CH2:9][CH2:10][NH:11][C:5]2=[N:4][CH:3]=1

Participants

4

Reactant 2

HCID 1068Dimethyl SulfideHCID 866594217-Bromo-1-(2-chloro-3,6-difluorobenzyl)-1,4-dihydropyrazino[2,3-b]pyrazine-2,3-dione

Product 1

HCID 866594227-Bromo-1-(2-chloro-3,6-difluorobenzyl)-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazineYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-bromo-1-(2-chloro-3,6-difluorobenzyl)-1,4-dihydropyrazino[2,3-b]pyrazine-2,3-dione (2.5 mmol, 1.0 g) in THF (5 mL) was added BH3.Me2S (7.5 mmol, 3.75 mL, 2.0 M in THF). The resulting solution was refluxed for 2 hrs under N2. Excessive BH3 was quenched by addition of MeOH at rt then heating the reaction mixture for 10 min. After volatile components were removed on rotavap, the residue was subjected to a silica gel column chromatography by using 4:1 ratio of CH2Cl2/MeOH (pre-saturated with ammonia gas) as eluents, furnishing 7-bromo-1-(2-chloro-3,6-difluorobenzyl)-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine in 20% yield (0.19 g).

Workup

  1. temperatureThe resulting solution was refluxed for 2 hrs under N2
  2. customExcessive BH3 was quenched by addition of MeOH at rt
  3. temperaturethen heating the reaction mixture for 10 min
  4. customAfter volatile components were removed on rotavap

Sources & evidence

ORD record
ord-db66337310a243fab069f774116a8f27
Source dataset
uspto-grants-2014_09
Patent number
US08846664B2

Reaction notes

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