Sodium Carbonate → 3-(3,5-Difluorophenyl)-N-methoxy-N,5-dimethylimidazo[1,2-a]pyridine-2-carboxamide

HRID 408791Notes

Reaction equation

HRID 408791 reaction equation
Br[C:2]1[N:6]2[C:7]([CH3:11])=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][C:3]=1[C:12]([N:14]([O:16][CH3:17])[CH3:15])=[O:13].[F:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[C:23]([F:25])[CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:18][C:19]1[CH:20]=[C:21]([C:2]2[N:6]3[C:7]([CH3:11])=[CH:8][CH:9]=[CH:10][C:5]3=[N:4][C:3]=2[C:12]([N:14]([O:16][CH3:17])[CH3:15])=[O:13])[CH:22]=[C:23]([F:25])[CH:24]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 583793113-bromo-N-methoxy-N,5-dimethylimidazo[1,2-a]pyridine-2-carboxamide

Product 1

HCID 866563283-(3,5-Difluorophenyl)-N-methoxy-N,5-dimethylimidazo[1,2-a]pyridine-2-carboxamideYield 81.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A solution of 3-bromo-N-methoxy-N,5-dimethylimidazo[1,2-a]pyridine-2-carboxamide (0.48 g, 1.6 mmol), (3,5-difluorophenyl)boronic acid (0.33 g, 2.1 mmol), and sodium carbonate (0.26 g, 2.4 mmol) in 1,4-dioxane (10 mL) and water (1.9 mL) was degassed with nitrogen and treated with tetrakis(triphenylphosphine)palladium(0) (0.13 g, 0.11 mmol). The reaction mixture was degassed with nitrogen and heated at 95° C. for 19 h. The reaction mixture was concentrated, diluted with ethyl acetate (100 mL), washed with water and brine, dried with sodium sulfate, filtered, and concentrated to a crude solid. Purification by flash column chromatography gave the desired product (0.43 g, 80%). LCMS for C17H16F2N3O2 (m+H)+: m/z=332.1.

Workup

  1. customThe reaction mixture was degassed with nitrogen
  2. concentrationThe reaction mixture was concentrated
  3. additiondiluted with ethyl acetate (100 mL)
  4. washwashed with water and brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to a crude solid
  8. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-e21b609afe5b4e6ab8ae38545b162c16
Source dataset
uspto-grants-2014_06
Patent number
US08759359B2

Reaction notes

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