Dimethylformamide → 5,6,7,8-tetrahydro-1,7-naphthyridine

Participants

Reaction Steps

7,8-Dihydro-1,7-naphthyridin-6(5H)-one of Formula I-m and 5,6,7,8-tetrahydro-1,7-naphthyridine of Formula I-n are synthesized as shown in Scheme 12. Compound LVII is reacted with 1 to 1.5 equivalents of sodium dimethylmalonate in a polar solvent such as NMP or DMF at from 50° C. to 110° C. to give diester of formula LVI. Decarboxylation of this material is accomplished by heating between 50° C. and 100° C. with 1 to 1.5 equivalents of lithium chloride in DMSO and 2 equivalents of water to give ester LV. Hydrogenolysis of LV in acetic acid with palladium on activated carbon gives lactam I-m which may be converted to compound of Formula I-n by treatment with hydride reducing agents such as borane-THF complex or lithium aluminum hydride in THF at from rt to reflux.

Provenance & Evidence