Aminolysis of Halogeno-1,6-Naphthyridines

The ease of aminolysis of halogeno-l,5-naphthyridines is governed by several factors already outlined for nucleophilic displacement in general (Section 3.2) and alcoholysis (Section 3.2.1). The examples that follow are divided according to the number and position(s) of the halogeno substituent(s). 

2-Chloro-3-nitro- (53, R = C1) gave 2-methylamino-3-nitro-l,5-naphthyridine (53, R = NHMe) (MeNH2, MeOH, 20°C, 1 h 58%).854 

2-Chloro-6-methyl- (54, R = Cl) gave 2-anilino-6-methyl- (54, R = NHPh) (neat PhNH2, reflux, 2h 95%) or 2-methyl-6-piperidino-l,5-naphthyridine [54, R = N(CH2)5] [neat HN(CH2)5, 180°C, sealed, 7h 30% (as picrate)].1051 

Also other examples.137,271 818,837 1036 3(7)-Halogeno-l,5-naphthyridines as Substrates 

Note Because they are essentially unactivated, these substrates would be expected to require vigorous conditions for aminolysis. 

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Many amino-1,5-naphthyridines have been made by primary synthesis (see Chapter 1), by aminolysis of halogeno-1,5-naphthyridines (see Section 3.2.2), or by aminolysis of 1,5-naphthyridinones (see Section 4.1.2). Others have been made by direct amination, as illustrated in the following examples. 

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