Sodium Nitrite → 6-((6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)-5,7-difluoroquinoline

HRID 1959760Notes

Reaction equation

HRID 1959760 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[C:11]([F:21])=[C:12]3[C:17](=[CH:18][C:19]=2[F:20])[N:16]=[CH:15][CH:14]=[CH:13]3)[C:5]([NH2:22])=[N:4][CH:3]=1.[N:23]([O-])=O.[Na+]>C(O)(=O)C.O>[Br:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:9][C:10]3[C:11]([F:21])=[C:12]4[C:17](=[CH:18][C:19]=3[F:20])[N:16]=[CH:15][CH:14]=[CH:13]4)[N:23]=[N:22][C:5]2=[N:4][CH:3]=1

Participants

5

Reactant 2

HCID 23668193Sodium NitriteHCID 866520516-bromo-N2-(5,7-difluoroquinolin-6-ylmethyl)pyrazine-2,3-diamine

Product 1

HCID 866520526-((6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)-5,7-difluoroquinolineYield 66%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Procedure

To a solution of 6-bromo-N2-(5,7-difluoroquinolin-6-ylmethyl)pyrazine-2,3-diamine (1.5 g, 4.10 mmol) in acetic acid (50 mL) and water (10 mL) was added a solution of sodium nitrite (283 mg, 4.10 mmol) in water (3 mL). After stirring at it for 3 h, the solvent was removed in vacuo, the residue was taken with NaHCO3 (aq.), extracted with CH2Cl2. The organic layer was washed with NH4Cl (aq.), dried over Na2SO4, filtered and concentrated in vacuo and purified by silica gel chromatography with hexanes:EtOAc to provide 6-((6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)-5,7-difluoroquinoline (1.02 g, 65%). 1H-NMR (400 MHz, CDCl3) δ ppm 8.99 (d, 1H), 8.79 (s, 1H), 8.43 (d, 1H), 7.65 (d, 1H), 7.49 (m, 1H), 6.13 (s, 2H). LCMS (method B): [MH]+=376.8, tR=2.23 min.

Workup

  1. customthe solvent was removed in vacuo
  2. extractionextracted with CH2Cl2
  3. washThe organic layer was washed with NH4Cl (aq.)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel chromatography with hexanes

Sources & evidence

ORD record
ord-eed05ed338e44f01b368089b7fd53d05
Source dataset
uspto-grants-2013_04
Patent number
US08410264B2

Reaction notes

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