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

HRID 15987

Reaction equation

HRID 15987 reaction equation
COCCOC.C([O-])([O-])=O.[Na+].[Na+].Br[C:14]1[N:19]=[C:18]2[N:20]([CH2:23][C:24]3[CH:25]=[C:26]4[C:31](=[CH:32][CH:33]=3)[N:30]=[CH:29][CH:28]=[CH:27]4)[N:21]=[N:22][C:17]2=[N:16][CH:15]=1.[F:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O>ClCCl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[C:14]1[N:19]=[C:18]2[N:20]([CH2:23][C:24]3[CH:25]=[C:26]4[C:31](=[CH:32][CH:33]=3)[N:30]=[CH:29][CH:28]=[CH:27]4)[N:21]=[N:22][C:17]2=[N:16][CH:15]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 547756086-((6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)quinoline

Product 1

HCID 593418296-((6-(2-fluorophenyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)quinolineYield 74.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of DME (3.0 mL) and 1 M aqueous Na2CO3 (0.88 mL) was degassed by bubbling in Argon for 10 minutes. The mixture was transferred via syringe to a vial containing 6-((6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)quinoline (100 mg, 0.29 mmol), 2-fluorophenylboronic acid (45 mg, 0.32 mmol) and Pd(dppf)2Cl2.CH2Cl2 (6.2 mg, 0.01 mmol). The vial was capped and heated to 80° C. for 3.5 hours. The crude reaction mixture was diluted with dichloromethane then washed with water. The dichloromethane was dried over Na2SO4, filtered and concentrated by rotary evaporation. The residue was purified by column chromatography using gradient elution with ethyl acetate and dichloromethane to afford 6-((6-(2-fluorophenyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)quinoline (77 mg, 74%).

Workup

  1. customwas degassed
  2. customby bubbling in Argon for 10 minutes
  3. customThe mixture was transferred via syringe
  4. customThe vial was capped
  5. customThe crude reaction mixture
  6. washthen washed with water
  7. dry with materialThe dichloromethane was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporation
  10. customThe residue was purified by column chromatography
  11. washelution with ethyl acetate and dichloromethane

Sources & evidence

ORD record
ord-809f753e12c145829877418314079bb0
Source dataset
uspto-grants-2010_06
Patent number
US07732604B2

Linked notes

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