Triphenylphosphine → 3-(5-Amino-2-methyl-phenyl)-7-methyl-1-phenyl-1H-[1,6]naphthyridin-2-one

HRID 424708Notes

Reaction equation

HRID 424708 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:26])=[C:6]([C:8]2[C:9](=[O:25])[N:10]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13](Cl)[CH:12]=3)[CH:7]=1.[CH:27]1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:26])=[C:6]([C:8]2[C:9](=[O:25])[N:10]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([CH3:27])[CH:12]=3)[CH:7]=1

Participants

4

Reactant 2

HCID 11776TriphenylphosphineHCID 592124543-(5-amino-2-methyl-phenyl)-7-chloro-1-phenyl-1H-[1,6]naphthyridin-2-one

Product 1

HCID 592125523-(5-Amino-2-methyl-phenyl)-7-methyl-1-phenyl-1H-[1,6]naphthyridin-2-one

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
140 °C

Procedure

A vial is charged with 19 (208 mg, 0.575 mmol), Pd2(dba)3 (26 mg, 0.028 mmol) and Ph3P (37 mg, 0.14 mmol). The vial is evacuated and refilled with N2. Dioxane (12 mL) is added to the vial and the solution is treated with AlMe3 (0.86 mL of a 2M solution in hexane, 1.72 mmol). The mixture is heated in a microwave oven at 140° C. for 20 min. The vial is cooled down to rt and the mixture is extracted with ethyl acetate. The organic phase is washed with 1N NaOH solution, saturated NaHCO3 solution and brine. The solvent is removed in vacuo and the crude product is purified using flash chromatography (hexane:ethyl acetate=2:1) to give 3-(5-amino-2-methyl-phenyl)-7-methyl-1-phenyl-1H-[1,6]naphthyridin-2-one 20. 1H NMR (400 MHz, CDCl3) δ 8.71 (s, 1H), 7.75 (s, 1H), 7.58-7.63 (m, 2H), 7.52-7.56 (m, 1H), 7.28-7.30 (m, 2H), 7.03 (d, 1H), 6.67 (d, 1H), 6.64 (d, 1H), 6.38 (s, 1H), 5.32 (s, 1H), 3.60 (brs, 2H), 2.46 (s, 3H), 2.18 (s, 3H).

Workup

  1. customThe vial is evacuated
  2. additionrefilled with N2
  3. additionDioxane (12 mL) is added to the vial and the solution
  4. additionis treated with AlMe3 (0.86 mL of a 2M solution in hexane, 1.72 mmol)
  5. temperatureThe vial is cooled down to rt
  6. extractionthe mixture is extracted with ethyl acetate
  7. washThe organic phase is washed with 1N NaOH solution, saturated NaHCO3 solution and brine
  8. customThe solvent is removed in vacuo
  9. customthe crude product is purified

Sources & evidence

ORD record
ord-9c9d2bc5b3334000b7caec00e46d6995
Source dataset
uspto-grants-2012_01
Patent number
US08106068B2

Reaction notes

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