Sodium Carbonate → (rac)-N-{1-[5-(7-Fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-yl]-ethyl}-propionamide

HRID 1774853Notes

Reaction equation

HRID 1774853 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.Br[C:24]1[CH:25]=[C:26]([CH:30]([NH:32][C:33](=[O:36])[CH2:34][CH3:35])[CH3:31])[CH:27]=[N:28][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+].C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][C:3]=1[C:24]1[CH:25]=[C:26]([CH:30]([NH:32][C:33](=[O:36])[CH2:34][CH3:35])[CH3:31])[CH:27]=[N:28][CH:29]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 86679131HCID 86679131, compoundHCID 89439879(rac)-N-[1-(5-Bromo-pyridin-3-yl)-ethyl]-propionamide

Product 1

HCID 89439881(rac)-N-{1-[5-(7-Fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-yl]-ethyl}-propionamideYield 20%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 7-fluoro-1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one (intermediate A-22, 168 g, 0.55 mmol) and (rac)-N-[1-(5-bromo-pyridin-3-yl)-ethyl]-propionamide (125 mg, 0.5 mmol) in DMF (3 mL), purged with argon for 1 min, was added bis(triphenylphosphine)palladium(II)chloride (38 mg, 0.054 mmol) and 1 N aq. Na2CO3 (2.5 mL). Then, the resulting reaction mixture was heated in a microwave at 100° C. for 45 min. After cooling to room temperature, it was diluted with EtOAc (5 mL), and poured into satd. aq. solution of NaHCO3 (10 mL). The aqueous layer was extracted with EtOAc (3×5 mL) and combined organics were washed with water and brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was the purified by prep-HPLC to give the title compound (35 mg, 20%) as a white solid. MS: 356.3 (M+H+)+.

Workup

  1. custompurged with argon for 1 min
  2. customThen, the resulting reaction mixture
  3. temperatureAfter cooling to room temperature
  4. additionpoured into satd
  5. extractionThe aqueous layer was extracted with EtOAc (3×5 mL)
  6. washcombined organics were washed with water and brine (20 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-0e72a2593bbd45ec88e706432545e82f
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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