Cesium carbonate → 2-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-6,8-difluoroquinoline

HRID 2035635Notes

Reaction equation

HRID 2035635 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([F:13])[CH:6]=[C:7]([F:12])[CH:8]=2)[N:3]=1.[N:14]1[N:15]=[CH:16][N:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=12.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:14]1[N:15]=[C:16]([C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[C:5]([F:13])[CH:6]=[C:7]([F:12])[CH:8]=3)[N:3]=2)[N:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=12

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 249770[1,2,4]Triazolo[4,3-a]pyridineHCID 642093072-Chloro-6,8-difluoroquinoline

Product 1

HCID 672304752-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-6,8-difluoroquinolineYield 59.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

2-Chloro-6,8-difluoroquinoline (0.025 g, 0.125 mmol) was combined with [1,2,4]triazolo[4,3-a]pyridine (0.016 g, 0.14 mmol), micronized Cs2CO3 (0.082 g, 0.25 mmol), and PdCl2(PPh3)2 (0.0088 g, 0.013 mmol), and the solids were slurried in dioxane (1.25 mL). The reaction was degassed with argon (bubbled through the solution) then heated to reflux for 20 hours. The crude reaction mixture was chromatographed without workup on SiO2 eluting with a gradient of 6% NH4OH in MeOH/ethyl acetate to provide the desired product as an orange solid (21 mg).

Workup

  1. customThe reaction was degassed with argon (
  2. custombubbled through the solution)
  3. temperaturethen heated
  4. temperatureto reflux for 20 hours
  5. customThe crude reaction mixture
  6. customwas chromatographed without workup on SiO2 eluting with a gradient of 6% NH4OH in MeOH/ethyl acetate

Sources & evidence

ORD record
ord-c8bb1749aedf4be48df7cbbeebf08ce1
Source dataset
uspto-grants-2013_11
Patent number
US08575145B2

Reaction notes

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