Isoxazolecarboxamide derivative

Isoxazolecarboxamide derivatives, (ni), effective as a1L-adrenoreceptor agonists were prepared by Leonardi (3) and were effective in treating incontinence as well as voiding problems such as weak stream and incomplete bladder emptying. 

The cycloaddition of Weinreb amide functionalized nitrile oxide with a range of dipolarophiles has been studied. N-Methoxy-N-methylcarbonocyanidic amide, nitrile oxide 207 (i.e., a nitrile oxide of Weinreb amide type derivative) was generated from 2-chloro-2-(hydroxyimino)-N-methoxy-N-methylacetamide as intermediate and used in situ. Thus, addition of 3-bromo-l-propyne as dipolarophile to this precursor of 207, followed by quenching with triethylamine, gave 5-(bromo-methyl)-N-(methoxy)-N-methyl-3-isoxazolecarboxamide 208 in 55% to 60% yield (367). 

Fenclorac also has an ionizable carboxylic acid group and exhibits a pH-independent region in its pH-rate profile above pH 4 due to intramolecular nucleophilic catalysis, as shown in Fig. 61.366 A similar pH-rate profile has been reported for the decarboxylation, accompanied by ring opening, of a derivative of isoxazolecarboxamide (Fig. 62).367... 

Figure 62. pH-rate profile for decarboxylation of a derivative of isoxazolecarboxamide. (Reproduced from Ref 367 with permission.)... 

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