Dimethylformamide → 2,2-Dimethyl-N-[5-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-yl]-propionamide

HRID 1774722Notes

Reaction equation

HRID 1774722 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])[CH:5]=[N:6][CH:7]=1.[CH3:15][N:16]1[C:25]2[C:20](=[CH:21][C:22](B3OC(C)(C)C(C)(C)O3)=[CH:23][CH:24]=2)[CH2:19][CH2:18][C:17]1=[O:35].CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>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>[CH3:11][C:10]([CH3:13])([CH3:12])[C:9]([NH:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([C:22]2[CH:21]=[C:20]3[C:25](=[CH:24][CH:23]=2)[N:16]([CH3:15])[C:17](=[O:35])[CH2:18][CH2:19]3)[CH:3]=1)=[O:14]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 24229189N-(5-Bromo-pyridin-3-yl)-2,2-dimethyl-propionamideHCID 722082331-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 866791042,2-Dimethyl-N-[5-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-yl]-propionamideYield 74.3%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with N-(5-bromopyridin-3-yl)pivalamide (0.2 g, 0.778 mmol), 1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one (intermediate A-1) (0.246 g, 0.856 mmol) and DMF (4 mL). The reaction mixture was purged with Argon; then, bis(triphenylphosphine)palladium(II)chloride (0.055 g, 0.078 mmol), followed by 1N aqueous Na2CO3 solution (2.33 mL, 2.33 mmol) were added and the reaction was heated in the microwave at 120° C. for 5 min. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2×20 mL). The resulting filtrate was washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.195 g, 74%) as a white solid. MS: 338.2 (M+H+).

Workup

  1. customThe reaction mixture was purged with Argon
  2. additionwere added
  3. filtrationfiltered through Dicalite
  4. washwashed with EtOAc (2×20 mL)
  5. washThe resulting filtrate was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customThe residue was purified by silica gel flash chromatography
  10. washeluting with a 0 to 5% MeOH-DCM gradient

Sources & evidence

ORD record
ord-332363a642e24ff38ae63dd309fe91f7
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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