Sulfuric Acid → 6-((6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)quinoline

HRID 15985

Reaction equation

HRID 15985 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][CH:14]=[CH:13]3)[C:5]([NH2:20])=[N:4][CH:3]=1.[N:21]([O-])=O.[Na+].S(=O)(=O)(O)O.[OH-].[Na+]>O.CC(O)=O>[Br:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:9][C:10]3[CH:11]=[C:12]4[C:17](=[CH:18][CH:19]=3)[N:16]=[CH:15][CH:14]=[CH:13]4)[N:21]=[N:20][C:5]2=[N:4][CH:3]=1

Participants

7

Reactant 4

HCID 1118Sulfuric Acid3×HCID 14798Sodium HydroxideHCID 23668193Sodium Nitrite3×HCID 457894186-bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamine

Product 1

HCID 547756086-((6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)quinolineYield 58.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent7×

Procedure

To a 6° C. mixture of 6-bromo-N2-(quinolin-6-ylmethyl)pyrazine-2,3-diamine (16 g, 48 mmol), AcOH (97 mL) and H2O (97 mL) was added NaNO2 (4.0 g, 58 mmol) in H2O (12 mL) dropwise over 15 min. After 1.5 hours, a 1:1 mixture of concentrated sulfuric acid and water (6 mL) was added dropwise. After 1.5 hours, NaNO2 (0.5 g, 7 mmol) in H2O (2 mL) and a 1:1 mixture of concentrated sulfuric acid and water (5 mL) were added. The reaction was allowed to warm to room temperature overnight. The reaction was re-cooled in an ice bath and over a period of 1.5 hours, a 1:1 mixture of concentrated sulfuric acid and water (30 mL) and NaNO2 (1.5 g, 22 mmol) in H2O (5 mL) was added. Aqueous 3.75 M NaOH (210 mL) was added dropwise and the resulting suspension was filtered. The precipitate was washed sequentially with water and ether, then suspended in dichloromethane:ethanol (1:1) and filtered. The filtrate was washed sequentially with 1M aqueous Na2CO3 and brine, dried over Na2SO4, filtered and concentrated by rotary evaporation to afford 6-((6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)quinoline (9.6 g, 58%).

Workup

  1. additionwas added dropwise
  2. waitAfter 1.5 hours
  3. additionwere added
  4. temperatureThe reaction was re-cooled in an ice bath and over a period of 1.5 hours
  5. additionwas added
  6. filtrationthe resulting suspension was filtered
  7. washThe precipitate was washed sequentially with water and ether
  8. filtrationfiltered
  9. washThe filtrate was washed sequentially with 1M aqueous Na2CO3 and brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-e96081d2cf5c4d08bafa6aac38b756fb
Source dataset
uspto-grants-2010_06
Patent number
US07732604B2

Linked notes

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