Amino-1,7-naphthyridines hydrolysis

Nitration of 2-amino-l,8-naphthyridin-5(8H)-one (67a) in acetic acid or in acetic anhydride does not occur in HNO3/H2SO4 the products obtained were difficult to separate (72GCI253). Hydrolysis of the amino group under nitration conditions has also been observed with 6- and 7-carboxy-2-aminonaphthyridin-5(8H)-ones (67b/67c), yielding the corresponding (68b/ 68c) (72GCI253). 

The hydrolysis of diethyl N-(6-phenyl-7-hydroxy-1,8-naphthyridin-2-yl)aminomethylenemalonate in aqueous sodium hydroxide afforded 2-amino-6-phenyl-7-hydroxy-l, 8-naphthyridine (69G677). 

Sawyer and Wibberley5 demonstrated that the product obtained by Singh et al.i2 in the reaction of 2-amino-4-methylpyridine and acetylacetone in polyphosphoric acid was not the naphthyridine but was instead the enamine of type 5, which was formed by hydrolysis of the pyrido[l,2-a]pyrimidinium salt (6) when the reaction mixture was neutralized. Formation of both isomeric pyrido[l,2-c<]pyrimidinium salts with asymmetric 1,3-diketones (R1 R2) was occasionally observed.3... 

The hydrolysis of amino-1,5-naphthyridines has been covered in Section 4.1.1. Other reported reactions are illustrated by the following examples. 

Methylamino-l,6-naphthyridine-3-carbonitrile (18, R = Me) underwent limited hydrolysis of its cyano group to afford 2-methylamino-l,6-naphthyridine-3-carboxamide (17) (KOH, H20, EtOH, reflux, 5 min 79%) the related substrate, 2-amino-l,6-naphthyridine-3-carbonitrile (18, R = H), underwent thiolysis of the cyano group to afford 2-amino-1,6-naphthyridine-3-car-bothioamide (19) (substrate, NEt3, pyridine, 20°C, H2S in, 2 h 97%) or hydrazinolysis of the cyano group to afford 2,N diamino -1,6-naphthyridine-3-carboxamidine (20) (H2NNH2.H2Q, reflux, 5 min 65%).247... 

Berninamycinic acid is one of the products from acid hydrolysis of the cyclic peptide antibiotic berninamycin A, which is a potent inhibitor of bacterial protein synthesis. Berninamycinic acid has been assigned the structure (524), anhydro-3,8-dicarboxy-6-hydroxythiazolo[2,3-/][l,6]naphthyridin-4-ium hydroxide. The 6-hydroxy group arises during hydrolysis from a peptide-bonded amino group (77JA1645). 

Condensation of 2-amino-3-bromo-l,6-naphthyridines 81 with potassium O-ethyl xanthate in A-methylpyrrolidone afforded thiazolo[4,5-6][l,6]naphthyridine-2(3//)-thiones 303 whose subsequent methylation and hydrolysis in the presence of sodium methoxide afforded thiazolonaphthyridones 304 inhibiting adenosine-3, 5 -cyclo-phosphate phosphodiesterase (cAMP PDE III) (1995JMC2546). 

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