Potassium Carbonate → Methyl 6-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-ethyl-2-methoxynicotinate

HRID 1481701Notes

Reaction equation

HRID 1481701 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([N:8]=[CH:9][N:10]=2)[CH:7]=1.[CH3:11]C([O-])=O.[K+].C([O-])([O-])=O.[K+].[K+].Cl[C:23]1[C:31]([CH2:32][CH3:33])=[CH:30][C:26]([C:27]([O-:29])=[O:28])=[C:25]([O:34][CH3:35])[N:24]=1>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].O>[N:10]1[CH:9]=[N:8][N:6]2[CH:7]=[C:2]([C:23]3[C:31]([CH2:32][CH3:33])=[CH:30][C:26]([C:27]([O:29][CH3:11])=[O:28])=[C:25]([O:34][CH3:35])[N:24]=3)[CH:3]=[CH:4][C:5]=12

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 115139346-Bromo-(1,2,4)triazolo(1,5-a)pyridineHCID 1317366566-Chloro-5-ethyl-2-methoxynicotinate

Product 1

HCID 71284266Methyl 6-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-ethyl-2-methoxynicotinate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×

Conditions

Temperature
130 °C

Procedure

6-bromo-[1,2,4]triazolo[1,5-a]pyridine (0.107 g, 0.54 mmol), bis(pinacolato) diborate (0.170 g, 0.67 mmol), Pd(dppf)Cl2 (15.8 mg, 0.02 mmol, 4 mol %), and KOAc (0.160 g, 1.63 mmol) were mixed together in a heat-gun dried vial. The vial was vacuumed and backfilled with argon before dioxane (1.6 mL) was added. The mixture was heated at 130° C. for ˜1 h until complete consumption of the starting bromide was observed. The reaction mixture was cooled to room temperature before H2O (0.20 mL), K2CO3 (0.220 g, 1.59 mmol) and 6-chloro-5-ethyl-2-methoxynicotinate (0.150 g, 0.65 mmol) were added. The reaction vial was resealed under argon and the mixture was heated at 120° C. for 3 h and then cooled to room temperature. Water (5 mL) was added to the reaction mixture and the product was extracted with DCM (3×5 mL). The combined organics were washed with NaCl (aqueous saturated, 5 mL) and dried over Na2SO4. After concentration of the solvent the residue was purified by column chromatography (EtOAc/hexanes, 0-100% gradient). Upon concentration of the desired fractions, the residue was treated with H2O (5 mL) and stirred vigorously for 30 min, the solid was then filtered and washed with H2O. Upon drying methyl 6-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-ethyl-2-methoxynicotinate (0.115 g, 69%) was obtained as pale yellow solid.

Workup

  1. customdried vial
  2. additionwas added
  3. additionwere added
  4. customThe reaction
  5. temperaturethe mixture was heated at 120° C. for 3 h
  6. temperaturecooled to room temperature
  7. extractionthe product was extracted with DCM (3×5 mL)
  8. washThe combined organics were washed with NaCl (aqueous saturated, 5 mL)
  9. dry with materialdried over Na2SO4
  10. customAfter concentration of the solvent the residue was purified by column chromatography (EtOAc/hexanes, 0-100% gradient)
  11. additionUpon concentration of the desired fractions, the residue was treated with H2O (5 mL)
  12. filtrationthe solid was then filtered
  13. washwashed with H2O
  14. dry with materialUpon drying methyl 6-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-ethyl-2-methoxynicotinate (0.115 g, 69%)
  15. customwas obtained as pale yellow solid

Sources & evidence

ORD record
ord-129664cc5c704f30a6ac1f5d62586dcf
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

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