Potassium Carbonate → tert-Butyl 4-({2-[4-(5-chloro-2-cyclopropylphenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]propanoyl}amino)benzoate

HRID 56841Notes

Reaction equation

HRID 56841 reaction equation
Br[C:2]1[C:7]([O:8][CH3:9])=[CH:6][N:5]([CH:10]([CH3:27])[C:11]([NH:13][C:14]2[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:16][CH:15]=2)=[O:12])[C:4](=[O:28])[CH:3]=1.[Cl:29][C:30]1[CH:31]=[CH:32][C:33]([CH:45]2[CH2:47][CH2:46]2)=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:35]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([CH:45]2[CH2:47][CH2:46]2)=[C:32]([C:2]2[C:7]([O:8][CH3:9])=[CH:6][N:5]([CH:10]([CH3:27])[C:11]([NH:13][C:14]3[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:16][CH:15]=3)=[O:12])[C:4](=[O:28])[CH:3]=2)[CH:31]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 601501992-(5-chloro-2-cyclopropylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 117622877tert-Butyl 4-{[2-(4-bromo-5-methoxy-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate

Product 1

HCID 117622860tert-Butyl 4-({2-[4-(5-chloro-2-cyclopropylphenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]propanoyl}amino)benzoate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Under argon (in a flask dried by heating), 125 mg (0.27 mmol) of tert-butyl 4-{[2-(4-bromo-5-methoxy-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate (racemate), 92 mg (0.33 mmol, 1.2 eq.) of 2-(5-chloro-2-cyclopropylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 114 mg (0.82 mmol, 3.0 eq.) of potassium carbonate and 22 mg (0.03 mmol, 0.1 eq.) of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct were suspended in 5.0 ml of dioxane and stirred overnight in an oil bath already preheated to 110° C. The reaction mixture was filtered through Celite and the residue was washed with dioxane. The combined filtrates were concentrated under reduced pressure. The residue was triturated with water, filtered off, washed with water, dried under reduced pressure and purified by flash chromatography (silica gel-50, cyclohexane/ethyl acetate gradient). Yield: 114 mg (79% of theory)

Workup

  1. customalready preheated to 110° C
  2. filtrationThe reaction mixture was filtered through Celite
  3. washthe residue was washed with dioxane
  4. concentrationThe combined filtrates were concentrated under reduced pressure
  5. customThe residue was triturated with water
  6. filtrationfiltered off
  7. washwashed with water
  8. customdried under reduced pressure
  9. custompurified by flash chromatography (silica gel-50, cyclohexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-059599e58ba94af5998f5f7aa72839b7
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

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