Réaction #77506

Équation de réaction

2-chloro-N-[3-(6-methoxy-pyridin-3-yl)-allyl]-nicotinamide

triethylamine

→

8-[(6-methoxy-pyridin-3-yl)-methyl]-6H-[1,6]naphthyridin-5-one

8-[1-(6-methoxy-pyridin-3-yl)-methylidene]-7,8-dihydro-6H-[1,6]naphthyridin-5-one

Rendement 25.0%

Solvants

DMF

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITis again effected for 24 h at 150° C
3. 3
   FiltrationThe mixture is filtered
4. 4
   Autrethe DMF is partially evaporated on a RE
5. 5
   workup.DISSOLUTIONThe residue is dissolved with EtOAc and diluted Na2CO3 solution
6. 6
   Autrethe water phase separated
7. 7
   Extractionextraction
8. 8
   LavageThe organic phases are washed with water and brine
9. 9
   Séchagedried (Na2SO4)
10. 10
    Concentrationconcentrated by evaporation

Mode opératoire

Under a N2 atmosphere, 1.02 g (3.36 mmol) of an (E/Z) mixture of 2-chloro-N-[3-(6-methoxy-pyridin-3-yl)-allyl]-nicotinamide, 995 mg (3.36 mmol) of tetrabutylammonium chloride, 1240 mg (3.36 mmol) of tetrabutylammonium iodide and 80 mg (0.36 mmol) of palladium diacetate are dissolved in 63 ml of DMF, then 1.2 ml (8.6 mmol) of triethylamine are added and stirring effected for 28 h at 150° C. in an ampulla. After adding a further 80 mg of palladium diacetate, stirring is again effected for 24 h at 150° C. The mixture is filtered and the DMF is partially evaporated on a RE. The residue is dissolved with EtOAc and diluted Na2CO3 solution, the water phase separated and extraction effected twice more with EtOAc/EtOH 9:1. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2, methylene chloride/EtOAc 1:1→EtOAc) yields 8-[(6-methoxy-pyridin-3-yl)-methyl]-6H-[1,6]naphthyridin-5-one A (contaminated with ca. 25% 8-[1-(6-methoxy-pyridin-3-yl)-methylidene]-7,8-dihydro-6H-[1,6]naphthyridin-5-one B); FAB-MS: (M+H)+=268; HPLC(gradient20-100) tRet=6.0/8.3; 1H NMR (CDCl3) i.a. δ4.12 (s, H2C—C(8) of A), 4.71 (d, 2.3 Hz, H2C(7) of B).

Source