3-methylisoxazole carboxylic acid

Acetylisoxazoles are converted to carboxylic acids by boiling with dilute nitric acid. This method allowed the development of a one-stage preparative method for 5-methylisoxazole-3-carboxylic acid (191) starting with acetonylacetone (190). ... 

Methylisoxazole-3-carboxylic acid chloride 4-(p-Aminoethyl)benzene sulfonamide hydrochloride Chloroformic acid methyl ester N-Amino-hexamethyleneimine... 

Properly substituted isoxazolecarboxylic acids can be converted into esters, acid halides, amides and hydrazides, and reduced by lithium aluminum hydride to alcohols. For example, 3-methoxyisoxazole-5-carboxylic acid (212) reacted with thionyl chloride in DMF to give the acid chloride (213) (74ACS(B)636). Ethyl 3-ethyl-5-methylisoxazole-4-carboxylate (214) was reduced with LAH to give 3-ethyl-4-hydroxymethyl-5-methylisoxazole (215) (7308(53)70). 

CP608039 (2S,3S,4R,5R)-3-amino-5 6-[5-chloro-2-(3-methylisoxazol-5-yhnethoxy)benzylamino]purin-9-yl-l-4-hydroxytetrahydrofuran-2-carboxylic acid methylamide... 

Fig. 2.4 Structures of agonists and antagonists of kainate receptors. 5-1 Will, 5-iodowillardiine (a) SYM 2081, (25,4R)-4-methylglutamate (b) 2S,AR isomer of 4-cinnamylglutamic acid (c) AMOA, (RS)-2-amino-3-(3-carboxymethoxy)-5-methylisoxazol-4-yl]propionic acid (d) AMNH, (RS)-2-amino-3-[2-(3-hydroxy-5-methylisoxazol-4-yl)-methyl-5-methyl-3-oxoisoxazo-lin-4-yl)]propionic acid (e) and LY 294486, (3SR,4aRS,6SR,8aRS)-6-[(lH-tetrazol-5-yl)methoxymethyl]-l,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid (f)...

The 3-o-chlorophenyl-5-methylisoxazole-4-carboxylic acid, from which the acid chloride was prepared, was obtained by hydrolysis of the ester product of the reaction between o-chlorobenzohydroxamic chloride and ethyl acetoacetate in methanolic sodium methoxide. Reaction with thionyl chloride gave the starting material. 

A solution 0.1 mole of 2-ethoxymethyleneacetoacetic acid 4-trifluoromethylanilide (30.1 g) in 60 ml of ethanol is added dropwise at 5-10°C to the mixture of 0.11 mole of hydroxylamine hydrochloride (7.65 g) in 50 ml of water and 0.11 mole of sodium hydroxide (4.4 g) in 10 ml of water. The mixture is heated under reflux for 15 min. The crystals which are precipitated after cooling are filtered off, washed with water and dried. 19.6 g (72.6% of theory) of crystalline 5-methylisoxazole-4-carboxylic acid 4-trifluoromethyl-anilide are thus obtained, melting point (after recrystallization from toluene) 166.5°C. 

Phenyl-5-methylisoxazole-4-carboxylic acid p-Methoxyphenyl p-Methylbenzylsulfonyl... 

Methylisoxazole-5-carboxylic acid was converted into the corresponding 5-carboxamides and 5-(l/7-pyrazol-l-ylcarbonyl) derivatives in satisfactory yields by treatment with thionyl chloride and amines or pyrazoles <2002SC425>. A three-component assembly of isoxazole-5-carboxylic acid chloride, 1,1-dimethylallene, and bis-pinacolatodiboron, catalyzed by a phosphine-free palladium complex, gave 2-acylallylboronate derivatives regiose-lectively (Equation 47) <2003JA12576>. On the other hand, a mild procedure allowed the preparation of /3,7-unsaturated ketones by simple reaction of 3-aryl-5-methylisoxazole-4-carboxylic acid chlorides with allyl bromide and indium in DMF (Equation 48) <1997TL8745>. 

Other reactions which form nitrile oxides or their cycloadducts from furoxans are known, but in the majority of these cases their course is not clear. 4-Phenylfuroxan with mild base rearranges to the isomeric a-oximino-phenylacetonitrile oxide (see Section VI). The distillation of 3-ethoxy-carbonylfuroxan-4-carboxylic acid (70) appears to generate the nitrile oxide 72, since one of the products isolated is diethyl furoxandicarboxylate (71).335,336 The diester (71) with anethole is reported to form ethyl 4-anisyI-5-methylisoxazole-3-carboxylate (73),337 but it is not established that the reaction involves the generation of 72 by dissociation of 71, as the authors suggested (see Section V,C,1). See also Section X. 

Scheme 3.9 Decarboxylative arylation of an imidazo[1,2-a]pyridine-3-carboxylic acid and an 3-(4-fluorophenyl)-5-methylisoxazole-4-carboxylic acid with aryl halides, as described by Lee and coworkers [21].

Resistance to 3-methylisoxazole-5-carboxylic acid (IX) has also been demonstrated. 32 This compound is similar to the corresponding pyrazole in that it depresses plasma FFA and glucose levels in fasted glucose-primed rats33, and the effect is lost after 2 days pretreatment. 32 Resistance to the isoxazole is also dependent on an intact pituitary-adrenal system. 32... 

Although no detailed studies on the mechanism of action of these newer pyrazoles and isoxazoles have been reportedi it seems quite likely that they act by the same mechanism as do the earlier compounds (5-metb-ylpyrazole-3-carboxylic acid and 3-methylisoxazole-5-carboxylic acid) and they are probably subject to the same limitations as the previously studied compounds. 

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