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

HRID 1774848Notes

Reaction equation

HRID 1774848 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]([CH2:30][NH:31][C:32](=[O:35])[CH2:33][CH3:34])[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>[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]([CH2:30][NH:31][C:32](=[O:35])[CH2:33][CH3:34])[CH:27]=[N:28][CH:29]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 86679131HCID 86679131, compoundHCID 86679194N-(5-Bromo-pyridin-3-ylmethyl)-propionamide

Product 1

HCID 86679195N-[5-(7-Fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylmethyl]-propionamideYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °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 N-(5-bromo-pyridin-3-ylmethyl)-propionamide (122 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 110° C. for 45 min. After cooling to room temperature, it was diluted with EtOAc (5 mL) and poured into a 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 then purified by prep-HPLC to afford the title compound (30 mg, 18%) as a white solid. MS: 342.1 (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 a 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. customThe residue was then purified by prep-HPLC

Sources & evidence

ORD record
ord-dd7dfea26d814da889e94f2031a8a8b2
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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