Dimethylformamide → 1-Methyl-6-(1,2,3,4-tetrahydro-1,7-naphthyridin-5-yl)-3,4-dihydroquinolin-2(1H)-one

HRID 530328Notes

Reaction equation

HRID 530328 reaction equation
Cl.Br[C:3]1[CH:12]=[N:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][CH2:7][NH:8]2.[CH3:13][N:14]1[C:23]2[C:18](=[CH:19][C:20](B3OC(C)(C)C(C)(C)O3)=[CH:21][CH:22]=2)[CH2:17][CH2:16][C:15]1=[O:33].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>[CH3:13][N:14]1[C:23]2[C:18](=[CH:19][C:20]([C:3]3[CH:12]=[N:11][CH:10]=[C:9]4[C:4]=3[CH2:5][CH2:6][CH2:7][NH:8]4)=[CH:21][CH:22]=2)[CH2:17][CH2:16][C:15]1=[O:33]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 713036555-Bromo-1,2,3,4-tetrahydro-1,7-naphthyridine hydrochlorideHCID 722082331-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 866799281-Methyl-6-(1,2,3,4-tetrahydro-1,7-naphthyridin-5-yl)-3,4-dihydroquinolin-2(1H)-oneYield 72.3%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with 5-bromo-1,2,3,4-tetrahydro-1,7-naphthyridine hydrochloride (0.1 g, 0.401 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, 0.127 g, 0.441 mmol) and DMF (2.5 mL). The reaction mixture was purged with Argon. Then, bis(triphenylphosphine)palladium(II)chloride (0.028 g, 0.040 mmol), followed by a 1N aqueous Na2CO3 solution (1.6 mL, 1.6 mmol) were added and the reaction mixture was heated in the microwave at 120° C. for 30 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 (0.085 g, 72%) as a white solid. MS: 294.2 (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-ffbba0d44ca14c1eb93bb5f0768e005d
Source dataset
uspto-grants-2016_05
Patent number
US09353081B2

Reaction notes

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