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

HRID 1478681Notes

Reaction equation

HRID 1478681 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-a11615bf05f34478a336de0277669600
Source dataset
uspto-grants-2016_08
Patent number
US09403847B2

Reaction notes

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