AbstractCondensation of 1H‐indole‐3‐ethanamines 1 with cyclic β‐keto esters 2 under azeotropic conditions followed by acid‐catalyzed ring closure of the resulting enamines 3 gave 2′,3′,4′,9′‐tetrahydrospiro[piperidine‐3,1′,‐[1H]pyrido[3,4‐b]indole] ‐4‐carboxylic acid alkyl esters 4. Condensation of 1 with 2‐acylcycloalkanones 8 gave two types of enamines, 10 and 11, respectively. Enamines 10 on treatment with acid gave 1‐(2′,3′,4′,9′‐tetrahydro‐3H‐pyrido[3,4‐b]indol‐1‐yl)‐1‐alkylcyclohexanols 17. Compounds 17 were further dehydrated to give cycloalkane derivatives 19.

A novel series of antiinflammatory agents, N-isoxazolyl-3-carboxamides of 4-hydroxy-2H-1,2-benzothiazine 1,1-dioxide, was synthesized and evaluated as antiinflammatory agents in the carrageenin-induced rat paw edema (CIRPE) assay and adjuvant-induced polyarthritis (AIP) assay. Several analogues were found to be equipotent or more potent than aspirin and phenylbutazone. Structure-activity relationships are discussed. One of the compounds, 4-hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl)-2H-1,2-benzothiazine 3-carboxamide 1,1-dioxide (3a; isoxicam), was found to be 3 times as potent as phenylbutazone in the CIRPE and in the therapeutic AIP assays. Isoxicam (3a) is presently undergoing phase III clinical trial as an antiarthritic drug.

AbstractA series of 4‐(2‐keto‐substituted)‐3,4‐dihydro‐3‐methyl‐2H‐1,3‐benzoxazin‐2‐ones 1 (Table I) was synthesized by condensation of 3‐alkyl‐3,4‐dihydro‐4‐hydroxy‐2H‐1,3‐benzoxazin‐2‐ones 4 with ketones 5 having active alpha hydrogens. In the presence of alcoholic potassium borohydride, compounds 1 underwent reductive transacylation to give 1,3‐oxazin‐2‐one derivatives 3 (Table III, a,b,c). When the other side of the ketone possessed substituents other than hydrogen, there were always also normal reduction products, i.e., secondary alcohols 2 (Table II) in addition to 3.

AbstractKondensationsreaktionen der 3‐Alkyl‐3,4‐dihydro‐4‐hydroxy‐2H‐1,3‐ benzoxazin‐2‐one (III) mit einer Vielzahl von β‐Ketoestern (II) und lß‐Diketonen, z.B. 2,4‐Pentandion (IV),zu den 4‐Derivaten (I) bzw. (V) werden beschrieben.

AbstractMit Amiden (II) erhält man aus den Oxazinonen (I) die Kondensationsprodukte (III), die zu den o‐substituierten Phenolen (IV) verseift werden.

AbstractThe multi‐step synthetic procedures to prepare a number of 2,3,4,5‐tetrahydro‐1H‐benzazepine derivatives 1 through a series of intermediates are described. The condensation of arylaldehydes2with 2‐nitropropanes3gave nitroalcohols4which were reduced to alcohol amines5. The condensation of5with arylacetaldehydes6gave imino derivatives7which on reduction with borohydride gave secondary amines8. By employing different methods, alcohol amines5were condensed with arylacetic acids9to give amides10which were then reduced to amines8. On treatment with mineral acids, amines8were cyclized to the target compounds1. Biological activities of1are also briefly discussed.

AbstractA series of 3,4‐Dihydro‐2‐oxo‐(3‐substituted‐2H‐1,3‐benzoxazin‐4‐yl)ureas (II, Table I) and 3,4‐dihydro‐2‐oxo‐(3‐substituted‐2H‐1,3‐benzoxazin‐4‐yl)thioureas (Table II) was prepared by treating 3,4‐dihydro‐4‐hydroxy‐3‐substituted‐2H‐1,3‐benzoxazin‐2‐ones with ureas and thioureas, respectively. In the presence of alcoholic alkali these compounds underwent transacylation to dihydro‐6‐(2‐hydroxyaryl)‐1,3,5‐triazine‐2,4‐(1H,2H)diones (Table III) and their 4‐thio analogues (Table IV).

AbstractRefluxing the oxime (1) of 2‐methyl‐2H‐1,2‐benzothiazin‐4(3H)one 1,1‐dioxide with tri‐fluoroacetic acid or with boron trifluoride in acetic acid gives the corresponding N‐acyl derivative (2 or 3) of 4‐amino‐2‐methyl‐2H‐1,2‐benzothiazin‐3(4H)one 1,1‐dioxide. This transformation appears to be related to the acid catalyzed conversion of α‐tetralone oxime to α‐naphthylamine.