N-(3-Bromo-6-fluoro-imidazo[1,2-a]pyridin-2-yl)-2,2,2-trifluoro-acetamide → N-(3-cyclopropyl-6-fluoro-imidazo[1,2-a]pyridin-2-yl)-2,2,2-trifluoro-acetamide

HRID 1971617Notes

Reaction equation

HRID 1971617 reaction equation
[Br-].[CH:2]1([Zn+])[CH2:4][CH2:3]1.Br[C:7]1[N:11]2[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]2=[N:9][C:8]=1[NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20]>O1CCCC1.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>[CH:2]1([C:7]2[N:11]3[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]3=[N:9][C:8]=2[NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 57607463N-(3-Bromo-6-fluoro-imidazo[1,2-a]pyridin-2-yl)-2,2,2-trifluoro-acetamide2×HCID 178419765HCID 178419765, compound2×

Product 1

HCID 57607458N-(3-cyclopropyl-6-fluoro-imidazo[1,2-a]pyridin-2-yl)-2,2,2-trifluoro-acetamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent3×

Procedure

Tetrakis(triphenylphosphine)palladium(0) (0.0797 g, 0.000069 mol) was added to a solution of 0.50 M of cyclopropylzinc bromide in tetrahydrofuran (4.1 mL) and N-(3-bromo-6-fluoro-imidazo[1,2-a]pyridin-2-yl)-2,2,2-trifluoro-acetamide (compound d, 0.225 g, 0.000690 mol) in tetrahydrofuran (20.0 mL) and the reaction was heated to reflux for 3 hours. An additional 0.50 M of cyclopropylzinc bromide (4.1 mL) in tetrahydrofuran and tetrakis(triphenylphosphine)palladium(0) (0.080 g) was added and the mixture was heated to reflux overnight. The reaction was concentrated in vacuo and crude product purified by column chromatography (50% ethyl acetate/hexanes) to give N-(3-cyclopropyl-6-fluoro-imidazo[1,2-a]pyridin-2-yl)-2,2,2-trifluoro-acetamide as a yellow solid. Rf 0.46, 50% ethyl acetate/hexanes; MS m/z 287 (M+H).

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 3 hours
  3. temperaturethe mixture was heated
  4. temperatureto reflux overnight
  5. concentrationThe reaction was concentrated in vacuo and crude product
  6. custompurified by column chromatography (50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-5804fb211cfc4a36b1793a263111b784
Source dataset
uspto-grants-2013_04
Patent number
US08431608B2

Reaction notes

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