Sodium Carbonate → N-{4-[1-sec-butyl-3-(4-chloro-2-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}propanamide

HRID 2359112Notes

Reaction equation

HRID 2359112 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16](=[O:19])[CH2:17][CH3:18])[CH:10]=2)O1.[CH:21]([N:25]1[CH:29]=[C:28](I)[C:27]([C:31]2[S:32][CH:33]=[C:34]([Cl:36])[CH:35]=2)=[N:26]1)([CH2:23][CH3:24])[CH3:22].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[CH:21]([N:25]1[CH:29]=[C:28]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16](=[O:19])[CH2:17][CH3:18])[CH:10]=2)[C:27]([C:31]2[S:32][CH:33]=[C:34]([Cl:36])[CH:35]=2)=[N:26]1)([CH2:23][CH3:24])[CH3:22]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 497605002-Propionamidopyridine-4-Boronic Acid Pinacol EsterHCID 672611621-sec-butyl-3-(4-chloro-2-thienyl)-4-iodo-1H-pyrazole

Product 1

HCID 67260463N-{4-[1-sec-butyl-3-(4-chloro-2-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}propanamideYield 99.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

N-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]propanamide (0.48 mmol) and bis(tricyclohexylphosphine)palladium(II) chloride (0.04 mmol) were weighed into a microwave vial (reaction volume 2-5 mL). A solution of 1-sec-butyl-3-(4-chloro-2-thienyl)-4-iodo-1H-pyrazole (0.40 mmol) in 3.0 mL degassed dioxane and 1.0 mL of a degassed 2 M aqueous sodium carbonate solution were added. The reaction mixture was purged with argon, the microwave vial was capped with a septum and transferred to a laboratory microwave oven. The reaction mixture was irradiated to a reaction temperature of 120° C. for 12 min. After cooling to room temperature, the reaction mixture was diluted with dioxane and filtered through a short pad of silica. The filtered solid was washed thoroughly with dioxane, ethyl acetate and dichloromethane. The combined filtrates were concentrated in vacuum. The residue was purified by chromatography on silica gel (cyclohexane:ethyl acetate 97:3 to 0:100) to afford 155 mg N-{4-[1-sec-butyl-3-(4-chloro-2-thienyl)-1H-pyrazol-4-yl]pyridin-2-yl}propanamide (99% yield).

Workup

  1. additionwere added
  2. customThe reaction mixture was purged with argon
  3. customthe microwave vial was capped with a septum
  4. customtransferred to a laboratory microwave oven
  5. customThe reaction mixture was irradiated to a reaction temperature of 120° C. for 12 min
  6. additionthe reaction mixture was diluted with dioxane
  7. filtrationfiltered through a short pad of silica
  8. washThe filtered solid was washed thoroughly with dioxane, ethyl acetate and dichloromethane
  9. concentrationThe combined filtrates were concentrated in vacuum
  10. customThe residue was purified by chromatography on silica gel (cyclohexane:ethyl acetate 97:3 to 0:100)

Sources & evidence

ORD record
ord-97c2937ec1ec4b9db1d9f141d5128bd1
Source dataset
uspto-grants-2014_04
Patent number
US08685974B2

Reaction notes

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