Potassium Carbonate → 5-(2-cyclopropylethylcarbamoyl)-3',6'-dihydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester

HRID 503821Notes

Reaction equation

HRID 503821 reaction equation
[CH:1]1([CH2:4][CH2:5][NH:6][C:7](=[O:15])[C:8]2[CH:13]=[CH:12][C:11](Cl)=[N:10][CH:9]=2)[CH2:3][CH2:2]1.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.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:1]1([CH2:4][CH2:5][NH:6][C:7]([C:8]2[CH:13]=[CH:12][C:11]([C:26]3[CH2:27][CH2:28][NH:23][CH2:24][CH:25]=3)=[N:10][CH:9]=2)=[O:15])[CH2:3][CH2:2]1.[C:16]([O:20][C:21]([N:23]1[CH2:24][CH:25]=[C:26]([C:11]2[CH:12]=[CH:13][C:8]([C:7](=[O:15])[NH:6][CH2:5][CH2:4][CH:1]3[CH2:3][CH2:2]3)=[CH:9][N:10]=2)[CH2:27][CH2:28]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 65558806HCID 65558806, compound

Product 2

HCID 684635775-(2-cyclopropylethylcarbamoyl)-3',6'-dihydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl esterYield 84.3%HCID 86617865HCID 86617865, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 6-chloronicotinic acid (2-cyclopropylethyl)amide (0.650 g, 2.893 mmol) in DMF (15 mL) was added 4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (1.075 g, 3.479 mmol), potassium carbonate (1.202 g, 8.697 mmol) and tetrakis(triphenylphosphine)palladium (0.347 g, 0.300 mmol). The resulting mixture was heated to 80° C. for 24 hours and then filtered. Ethyl acetate (40.0 mL) was added to the mixture and the organic solution was washed with water (20 mL), saturated NaCl (20 mL), dried over MgSO4 and then concentrated in vacuo. The crude product was purified by column chromatography to yield the desired product, 5-(2-cyclopropylethylcarbamoyl)-3′,6′-dihydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (0.453 g, 42%).

Workup

  1. filtrationfiltered
  2. additionEthyl acetate (40.0 mL) was added to the mixture
  3. washthe organic solution was washed with water (20 mL), saturated NaCl (20 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-b65ba56c3883409bb1766455558e5d3a
Source dataset
uspto-grants-2010_08
Patent number
US07777036B2

Reaction notes

Loading…