3-Amino-4-hydroxycoumarin

Hydrogenation of 4-hydroxy-3-methoxycarbonyl-6-oxo-l, 2(6/f)-oxazine (122) in methanol over palladium-charcoal has been shown to give 2,5-dimethoxy-carbonyl-3,6-dimethylpyrazine (501) and 3-amino-4-hydroxycoumarin (123, R = r2 = H), 3-amino4-hydroxy-6,8-dimethylcoumarin and 3-acetamido-4-hydroxy-6-methylcoumarin, when heated vrith 2N sodium hydroxide, gave... 

Ueda and co-workers at Bristol-Myers used mild acid hydrolysis to cleave the oxazole moiety in oxazolocoumarins to produce 3-amino-4-hydroxycoumarins. 

Suitably protected amino acids (112) (cysteine, serine, and lysine) have been added via the side-chain heteroatom (S, O, and N, respectively) to conjugated alkynones, alkynoic ester and alkynoic amide (113). The expected heterosubstituted vinyl product (114) was formed in each case, mainly as the ii-isomer. In an accompanying paper, this type of addition was applied to the derivatives of fluorescein, 7-hydroxycoumarin, Sudan 1, and dansyl chloride with linker arms containing a conjugated terminal alkyne. 

Benzoquinone reacted with dialkyl aminocrotonate to give 3-amino-4-carbalkoxy-6-hydroxycoumarin (90J HCl 447). 

Aliphatic primary and secondary amines attack the 1,2-bond of coumarins to give various derivatives depending on the reaction conditions and substituents on the substrate. In addition to the expected amides (280) from coumarin itself, some /3-amino amides (281) are obtained from 4-hydroxycoumarin. In addition, the latter reacts with secondary aliphatic and primary aromatic amines to yield substitution products such as 4-piperidinocoumarin... 

Treatment of the acid chloride (401) with sodium azide yields a 4-azidocoumarin (73CR(C)(276)1603) and acid hydrolysis of the carbamate (402) gives 4-hydroxycoumarin indicating that an amino group stabilizes a pyran-4-one structure better than does a hydroxy... 

This synthesis involves Michael cycloaddition reaction of the readily available 4-hydroxycoumarine 1 with a cyanocrotonitrile 2 in ethanolic piperidine to afforded 2-amino-3-cyano-4-methyl-4H, 5H-pyrano-benzopyran-5-one (3). Treatment of 3 with acetic anhydride for 0.5 h and/or 3 h under reflux afforded N-acetyl and [l]benzopyrano[3/,4/ 5,6]pyrano(2,3-d) pyrimidine-6,8-dione derivatives (4) and (5a), respectively. Also, interaction of 3 with benzoyl chloride or formic acid gave the corresponding pyrimidine derivatives (5b,c) while its treatment with formamide afforded the aminopyrimi-dine derivative (6). 

Disposition in the Body. Readily absorbed after oral administration. It is extensively metabolised by reduction to a number of metabolites including the amino derivative, and the two diastereoisomers of 4-hydroxy-3-[l-(4-nitrophenyl)-3-hydroxy-butyl]coumarin. Two further inactive metabolites, the 6-hydroxy- and 7-hydroxycoumarin derivatives have been identified in urine. About 50 to 60% of a dose is excreted in the urine in 48 hours, mostly as metabolites, with less than 1% as unchanged drug about 30% of a dose is eliminated in the faeces. 

A third ring was fused to 3-hydroxycoumarin by its reaction with benzyl-ideneacetone to give the ketone (197), which cyclized to the pyranobenzo-pyran (198) under acetylation conditions. Treatment of 3-amino-7-hydroxycoumarin with bromoacetone and cyclization of the product has given psoralen derivatives such as (199). In a new example of the addition... 

Hydroxyindoles. A soln. of dimethyl N-methylaminofumarate in anhydrous ether treated with a mixture of p-benzoquinone and BFg-etherate in the same solvent, and allowed to stand overnight -> dimethyl 5-hydroxy-l-methylindole-2,3-dicarboxylate. Y S2%. F. e. s. G. Domsdhke, J. pr. 311, 807 (1969) also 3-amino-6-hydroxycoumarins s. ibid. 311, 786, 800. 

Addition of naphthoquinone (178) to jS,y-unsaturated esters R CH=CHC0C02R, catalysed by the rrani-indane amino-thiourea (182), produced (183) as a result of the subsequent hemiketalization (<98% ee) An analogous addition of 0 4-hydroxycoumarin to a-enones, catalysed by the amino-thioiuea (184), afforded the warfarin-type adducts in <95% As a variation of the same theme, the 0... 

Bazgir et al. (2010) developed a simple, facile, and efficient three-component procedure for the synthesis of spiro[indoline-3,4 -pyrazolo[3,4-fc]pyridine]-2,6 (TFT)-diones (179) by the reaction of 4-hydroxycoumarins (176), isatins (177), and 5-amino-lH-pyrazoles (178) in water as an environmentally benign solvent, using p-toluenesulfonic acid as an inexpensive and readily available catalyst under ultrasonic irradiation (Scheme 8.58). 

Wang et al. s synthesis In 2011, a simple chiral primary amine thiourea bifunctional catalyst was introduced to the asymmetric Michael addition of 4-hydroxycoumarin to enones (Table 9.15). With Wang et al. s catalyst, l-[(15, 25)-2-amino-l,2-diphe-nylethyl]-3-benzylthiourea, all Michael additions could be smoothly performed to afford Michael... 

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