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

HRID 41876Notes

Reaction equation

HRID 41876 reaction equation
[CH3:1][C:2]([CH3:9])([C:6]([O-])=O)[C:3]([O-])=O.[Na+].[Na+].[CH3:12][N:13]1[C:17](=O)[CH2:16][CH2:15][CH2:14]1.[CH3:19][N:20]([CH:22]=[O:23])[CH3:21]>>[N:13]1[C:6]2[CH2:19][NH:20][C:22](=[O:23])[CH2:3][C:2]=2[CH:9]=[CH:15][CH:14]=1.[N:13]1[C:12]2[CH2:22][NH:20][CH2:21][CH2:1][C:17]=2[CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 13387N-methyl-2-pyrrolidoneHCID 15452843HCID 15452843, compound

Product 2

HCID 113562255,6,7,8-tetrahydro-1,7-naphthyridineHCID 67971946HCID 67971946, compound

Procedure

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.

Sources & evidence

ORD record
ord-22784cf479534ac9b71c897743b9a3b5
Source dataset
uspto-grants-2013_09
Patent number
US08536164B2

Reaction notes

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