Phenylacetonitrile → 2-Amino-5,7-diethyl-3-phenyl-1,6-naphthyridine

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][CH3:9])[N:5]=[C:4]([CH2:10][CH3:11])[C:3]=1[CH:12]=O.[OH-].[Na+].[C:16]1([CH2:22][C:23]#[N:24])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(O)C>[NH2:24][C:23]1[C:22]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:12][C:3]2[C:2](=[CH:7][C:6]([CH2:8][CH3:9])=[N:5][C:4]=2[CH2:10][CH3:11])[N:1]=1

Participants

Procedure

A mixture of 4-amino-2,6-diethylpyridine-3-carbaldehyde (2.2 g), ethanol (26 ml), aqueous sodium hydroxide solution (10% w/v; 2.2 ml) and phenylacetonitrile (3.8 ml) was heated at reflux for 2 hours. Volatile material was removed by evaporation and the residue was partitioned between ethyl acetate and 2M hydrochloric acid. The organic phase was separated and discarded. The aqueous phase was adjusted to pH 6 with solid sodium carbonate and then extracted twice with dichloromethane. The combined extracts were dried (MgSO4) and solvent was removed by evaporation to give 2-amino-5,7-diethyl-3-phenyl-1,6-naphthyridin (B) as a pale yellow solid (3.2 g); m.p. 109.5°-112° C.; NMR (d6 -DMSO): 1.27(t, 3H), 1.28(t, 3H), 2.77(q, 2H), 3.09(q, 2H), 6.41(broad, 2H), 7.05(s, 1H), 7.4-7.6(m, 5H), 7.96(s, 1H); mass spectrum (+ve FAB, methanol/NBA): 278 (M+H)+ ; microanalysis, found: C, 68.1; H, 6.5; N, 13.1%; C18H19N3.HCl.0.25H2O requires: C, 68.0; H, 6.5; N, 13.2%.