TETRACYCLINES

摘要

1298508 Tetracyclines RESEARCH CORP 8 June 1970 [12 June 1969] 27595/70 Headings C2A and C2C Novel tetracyclines of the formulµ wherein R 1 is H or OH, R 2 is H or halogen, R 3 is H or CH 3 , R 4 is dimethylamino or benzamido, and R 5 is H or C 1-4 alkyl are prepared by condensing azlactones or thiazolones of the formulµ with the appropriate methyl 3-oxoglutaramate, and, if desired hydroxylating the resulting products, converting the benzamido groups present into dimethylamino groups, removing the methoxy group at the 10-position, and the protective group on the amide nitrogen. The following intermediates are prepared: methyl 8 - chloro - 5 - methoxy - 4 - oxo - 1,2,3,4- tetra - hydro - 2 - naphthoate, methyl 8 - chloro- 4,4 - ethylenedioxy - 5 - methoxy - 1,2,3,4- tetrahydro - 2 - naphthoate, 8 - chloro - 4,4- ethylenedioxy - 2 - (2 - hydroxyethyl) - 5 - methoxy - 1,2,3,4 - tetrahydronaphthalene, 8- chloro - 2 - (2 - cyanoethyl) - 4,4 - ethylenedioxy - 5 - methoxy - 1,2,3,4 - tetrahydronaphthalene, 8 - chloro - 2 - (2 - formylethyl)- 5 - methoxy - 4 - oxo - 1,2,3,4 - tetrahydronaphthalene, 4 - [2 - (8 - chloro - 5 - methoxy- 4 - oxo - 2 - naphthyl)ethylidene] - 2 - phenyl- 2 - oxazolin - 5 - one, N - t - butyl - 4 - benzamido - 7 - chloro - 1,4,4a,5,5a,6,11,12a - octahydro - 3,12 - dihydroxy - 10 - methoxy- 1,11 - dioxo - 2 - naphthacenecarboxamide, N- t - butyl - 4 - benzamido - 7 - chloro - 1,4,4a,5,- 5a,6,11,12a - octahydro - 3,12,12a - trihydroxy- 10 - methoxy - 1,11 - dioxo - 2 - naphthacenecarboxamide, N - t - butyl - 4 - amino - 7- chloro - 1,4,4a,5,5a,6,11,12a - octahydro- 3,12,12a - trihydroxy - 10 - methoxy - 1,11- dioxo - 2 - naphthacenecarboxamide hydrochloride, and N - t - butyl - 7 - chloro - 4 - dimethylamino - 1,4,4a,5,5a,6,11,12a - octahydro - 3,12,12a - trihydroxy - 10 - methoxy- 1,11 - dioxo - 2 - naphthacenecarboxamide hydrochloride.