Oxazolo quinolines

The reduction of 2, either catalytically or with zinc in acetic acid, leads to 3-amino-4-hydroxy-2-quinolone 20 [72TH000], These amino compounds are rather unstable they dimerize with loss of ammonia to "bis-amines", which in turn are readily oxidized to dyes similar to those obtained from ninhydrin and primary amines [68M1205] [68M1543], The amino derivatives 20 are therefore conveniently converted into 0,N-diacetyl derivatives, the N-acetyl derivative 21, or its dehydrated form, the oxazolo derivative 22 [95MI000], The variety of biological activity of oxazolo-quinolines of type 22 has been detected only in recent years [94JHC1647],... 

H,4H-Oxazolo[5,4,3-y]pyrido[3,2-g]quinolin-4-one, 8-hydroxymethyl-6-methyl — see Nybomyein 5H-Oxazolo[2,3-[Pg.731]

A series of 2-aryloxazolo[4,5-/i]quinoline-5-arylidines was prepared by the reaction of 5,7-diamino-8-hydroxyquinoline with aromatic or aliphatic aldehydes in the presence of a basic catalyst such as piperidine. On the other hand, 2-styryl-5-diacetylamino-oxazolo[4,5-/i]quinolines were prepared by interaction of 2-methyl-5-diacetylamino-oxazolo[4,5-/i]quinoline with aromatic aldehydes (77MI1, 82MI2) (Scheme 6). 

Chloro-oxazolo[4,5-/i]quinoline-2-carboxylic acid methyl ester was the most active compound in tests for inhibitors of antigen-induced release of histamine in vitro from rat peritoneal mast cells (IC50 of 0.3 p,M) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (ED50 (intraperitoneal) of 0.1 mg/kg in dose 0.5 mg/kg as an inhibitor of the test)—10 times and 60 times more potent, respectively, than the disodium salt of cromoglycic acid (85JMC1255). 

Interaction of 6,7-dichloroquinoline-5,8-dione with amides in ethylene glycol afforded oxazolo[4,5-g]quinoline-4,9-dione, a compound with activity against Gram-positive bacteria (no data) (90MI2). 

Several 7-substituted (H, halogen, alkoxy, alkylthio, halogen, alkyl, carboxyl) oxazolo[5,4-/i]quinolines were found to be very effective against broadleaf weeds (90EUP1, 90GEP1). 

Treatment of quinoline with ethylene oxide gave oxazolo[3,2-u]quinoline 597 whereas 2-methylquinoline did not react with ethylene oxide (79JOC285). The oxazolidine 597 is labile as monitored by H NMR spectroscopy its colorless solution in CDCI3 became dark red within several hours (Scheme 100). 

Thermal cyclization of the arylaminomethylenemalonate afforded quinoline 3-carboxylate 630 whose reaction with 1,1-dibromoethane gave oxazolo[5,4,3-(/]quinoline 631. Acid hydrolysis and reaction with N-methylpiperazine gave 632 whose bactericidal activity is superior to that of pipemidic acid (82JAPK57203085) (Scheme 108). 

The most efficient routes to the cationic oxazolo[3,2- ]pyridine ring system 351 rely on the method of Bradsher and Zinn <1967JHC66> involving the cyclocondensation of iV-phenacyl-2-pyridones 349 obtained by alkylation of readily available 2-pyridones 347 (Scheme 95). This method has been used by Babaev et al. to prepare a series of 6-nitro-oxazolo[3,2- ]pyridines 355 from 5-nitro-2-pyridone 352 in excellent yields <2003MOL460>. Similarly, tricyclic oxazolo[3,2- ]pyridines 359 have been prepared from the corresponding quinolin-2(177)-ones 356 <2003H(60)131>. 

I3C-NMR spectroscopic data of heteroanalogs of bicyclo[4.4.0]decane, collected prior to 1983, have been summarized25 77. Therefore, only a selection of subsequent studies is noted. H- and 13C-NMR spectra of diastereomeric substituted cis- and rraw-4-hydroxy-l-oxabicyclo[4.4.0]-decanes642, as well as H-NMR spectra of isomeric perhydrooxazolo[3,4-a]quinolines 3 and 3,3a,4,5-tetrahydro-1 //-oxazolo[3,4-a]quinolines 4, have been discussed 643. The 3H data of five diastereomeric 5-methyl-3-phenyl-2,4-dioxabicyclo[4.4.0]decanes have been reported644. 

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