Dichloromethane → 7-(4-chlorophenyl)-2-((2-ethyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2101334

Reaction equation

HRID 2101334 reaction equation
Cl[C:2]1[C:7]([CH2:8][N:9]2[C:30](=[O:31])[N:12]3[CH:13]=[CH:14][C:15]([C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=4)=[C:16]([C:17]4[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=4)[C:11]3=[N:10]2)=[CH:6][CH:5]=[C:4]([C:32]([F:35])([F:34])[F:33])[N:3]=1.[CH2:36]([Zn]CC)[CH3:37].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CCOC(C)=O.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].C1COCC1>[Cl:29][C:26]1[CH:25]=[CH:24][C:23]([C:15]2[CH:14]=[CH:13][N:12]3[C:30](=[O:31])[N:9]([CH2:8][C:7]4[C:2]([CH2:36][CH3:37])=[N:3][C:4]([C:32]([F:34])([F:35])[F:33])=[CH:5][CH:6]=4)[N:10]=[C:11]3[C:16]=2[C:17]2[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=2)=[CH:28][CH:27]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 160048102-((2-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-7-(4-chlorophenyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneHCID 178418750HCID 178418750, compound

Product 1

HCID 160053477-(4-chlorophenyl)-2-((2-ethyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneYield 50.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-((2-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-7-(4-chlorophenyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (22 mg, 0.043 mmol), anhydrous THF (0.5 mL), diethylzinc (1.1 M solution in toluene, 0.059 mL, 0.065 mmol), solid K2CO3 (18 mg, 0.129 mmol) and Pd(dppf)Cl2.CH2Cl2 (7 mg, 0.0086 mmol) in a sealed tube was stirred at 80° C. for 16 h. After cooling to room temperature, the reaction mixture was diluted with EtOAc, washed with water, then saturated aqueous NaCl, dried over Na2SO4 and concentrated under reduced pressure. Two products were purified using preparative reverse phase HPLC (Phenomenex Luna 5 μm C-18 21.2×100 mm column eluted with a linear gradient of 50% to 80% B over 10 min (A=0.1% trifluoroacetic acid, 90% water, 10% methanol and B=0.1% trifluoroacetic acid, 90% methanol, 10% water) with flow rate at 20 mL/min and UV detection at 220 nm). HPLC fractions were concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with saturated aqueous NaHCO3 once, water twice, then saturated aqueous NaCl, dried over Na2SO4 and evaporated. The residue was dissolved in acetonitrile, frozen and lyophilized to afford 7-(4-chlorophenyl)-2-((2-ethyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (11 mg) and the title compound (7 mg) as a yellow powder. Title compound: HPLC/MS: retention time=3.20 min, [M+H]+=504.3.

Workup

  1. washwashed with water
  2. dry with materialsaturated aqueous NaCl, dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customTwo products were purified
  5. washeluted with a linear gradient of 50% to 80% B over 10 min (A=0.1% trifluoroacetic acid, 90% water, 10% methanol and B=0.1% trifluoroacetic acid, 90% methanol, 10% water) with flow rate at 20 mL/min and UV detection at 220 nm)
  6. concentrationHPLC fractions were concentrated under reduced pressure
  7. dissolutionThe residue was dissolved in EtOAc
  8. washwashed with saturated aqueous NaHCO3 once
  9. dry with materialwater twice, then saturated aqueous NaCl, dried over Na2SO4
  10. customevaporated
  11. dissolutionThe residue was dissolved in acetonitrile
  12. temperaturefrozen

Sources & evidence

ORD record
ord-e3e16d8ff938487f954c823ed088ec03
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Linked notes

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