Uprawniony z patentu: C. H. Boehringer Sohn, Ingelheim (Republika Federalna Niemiec) Sposób wytwarzania nowych 5-arylo-lH-l,5-benzodiazepino-2,4- -dionów Przedmiotem wynalazku jest sposób wytwarzania nowych 5-arylo-lH-l,5-ibenzodiazepino-2,4-dionów o ogólnym wzorze 1, w którym Rx oznacza prosty lub rozgaleziony rodnik alkilowy o 1—4 atomach wegla, ewentualnie podstawiony atomem chlorow¬ ca lub grupa hydroksylowa, alkoksylowa albo acy- loksylowa, grupa dwualkiloaminowa o 2—4 ato¬ mach wegla lub grupa piperydynowa, polaczona atomem azotu z lancuchem alkilowym, lub Rj ozna¬ cza rodnik allilowy ewentualnie podstawiony jed¬ na lub dwoma grupami metylowymi albo atomem chloru, rodnjlk cykloheksylowy, luib rodnik cyklo- alikalometylowy, rodnik fenylowy, ewentualnie pod¬ stawiony jedno- lub dwukrotnie grupa metylowa lub metoksylowa albo atomem chlorowca, rodnik fenyloalkilowy o 7—8 atomach wegla, R2 oznacza atom wodoru albo rodnik metylowy, R3 oznacza rodnik o wzorze 2, rodnik naftyIowy, piry- midynylowy, tienylowy, lub pirydylowy, przy czym ten ostatni moze byc podstawiony gru¬ pa metylowa . lub atomem chlorowca, R4 ozna¬ cza atom wodoru, grupe metylowa, metoksylo¬ wa, trójfluorometylowa lub nitrylowa, atom chlo¬ rowca albo ndzsza 'grupe acylowa lub alkoksykar- bonylowa o 1 lub 2 atomach wegla, R5 oznacza atom wodoru, grupe metylowa, etylowa, metoksy¬ lowa, trójfluorometylowa, nitrylowa lub nitrowa, atom chlorowca albo nizsza grupe acylowa lub al- koksykarbonylowa i R6 oznacza atom wodoru, gru¬ pe metylowa, etylowa lub metoksylowa albo atom chlorowca.Sposób wedlug wynalazku polega na arylowa- niu lub heteroarylowaniu przy 5 atomie azotu 5 lH-l,5-tbenzodiazepino-2,4-dionu o ogólnym wzorze 3, w którym Rx, R2 i R4 maja wyzej podane zna¬ czenie, a Y oznacza atom wodoru, metalu alkalicz¬ nego lub grupe acylowa, zwiazkiem o ogólnym wzorze X-R3, w którym R3 ma wyzej podane zna- 10 tczende, a X oznacza atom chlorowca.Arylowanie przeprowadza sie w obecnosci prosz¬ ku miedziowego, soli miedzi jedno- lub dwuwar¬ tosciowej albo ich mieszanin, badz przy zastosowa¬ niu halogenku arylu o ogólnym wzorze X-R3 w is nadmiarze, lulb tez w polarnych aprotycznych roz- puszczaitoiikach, jak np. dwumetyloformamid, sul- fotlenek dwuimetylowy albo amid szesciometylo- fosforowy. Stosujac rozpuszczalniki, dodaje sie ha¬ logenek arylu jedynie w obliczonej ilosci. Tempe- 20 ratura reakcji zalezy od uzytych kazdorazowo sub¬ stancji wyjsciowych i wynosi na ogól 90—180°C.W przypadku stosowania zwiazków o ogólnym wzorze 3, w którym Y oznacza atom wodoru lub grupe acylowa, konieczne jest dodanie odpowied- 25 niej zasady organicznej lub nieorganicznej, np. we¬ glanu, wodoroweglanu lub alkoholanu metalu al¬ kalicznego, lub korzystnie octanu metalu alkalicz¬ nego w ilosciach molowych albo w nadmiarze w celu zwiazania powstajacego chlorowodoru. 30 Podstawiony czlon l,5nbenzodiazepino-2,4-ddonów 8017180171 3 jest znany od roku 1906 (R. Mayer, Annalen der Chemie, tom 347, str. 17) i zostal iblizej zbadany przez J. Biichi i wspólpracowników (Helvetica Chimica Acta, tom 39, str. 957, r. 1956). Przy tym czlonie pierscieniowym pod dzialaniem kwasów nastepowalo latwo rozszczepienie pierscienia lub zwezenie pierscienia do imidazolu (J. Am. Chem.Soc, tom 66, str. 1810, r. 1910).Stwierdzono ponadto, ze w obecnosci alkohola¬ nów metali alkalicznych nastepuja równiez latwo przegrupowania do oenzimidazolonów. Tym bar¬ dziej nieoczekiwane bylo odkrycie, ze ten nietrwa¬ ly czlon pierscieniowy utrzymuje sie wobec sto¬ sunkowo ostrych warunków przedstawionej tutaj rezek^ji- aryilow-anta:-^ iw* faAypaaku^gfiM w zwiazku o ogólnym wzo- rle 1 Rj oznacza gr^pe hydroksyalkilowa, mozna dldatkowo ^ przeprowadzic grupe hydroksylowa ^ZJMt^lffii0^1^'jpfezoalfcanem w abecnosci ete- iwi u burowetgo^w-gglrpe alkdksylowa.W zwiazku o ogólnym wzorze 1, w którym Ri oznacza rodnik allilowy ewentualnie podstawiony jedna ilub dwoma grupami metylowymi lub aito- mem chloru mozna takze ten rodnik Rx poddac uwodornieniu w znany sposób.Stosowane jako substancje wyjsciowe lH-l,5-ben- zodiazepino-2,4-diony isa nowe. Mozna je otrzymac np. przez reakcje odpowiednio podstawionej 2-ni- troaniliny z halogenkiem estru monoalkilowego kwasu -malonowego, redukcje utworzonego anilidu estru alkilowego kwasu 2-nitromalonowego i cykli- zacje anilidu estru etyllowago kwasu 2-nitromalo¬ nowego wedlug zalaczonego schematu.W opisany sposób mozna otrzymac np. naste¬ pujace produkty koncowe: lHmetylo-5-fenylo-7- -trójfluoirometyilo-lH-l,5-lbenzodiazepino-2,4-(3H,5H)- -dion, 7-chloro -1 - metylo-5-(2-pirydylo) - 1H - 1,5- Jbenzodiazepino-2,4-(3H, 5H)-dion, 7-chloro-l-me- tylo-5-fenylo -1H -1,5 - benzodiazepino - 2,4 - (3H, 5H)- -dion, 7-chloro-1-metyló-5- (1-naftylo)-1H-1,5-ben- zodiazepino-2,4-(3H,5H)-dion, 7-chloro-l-metylo-5-(2- -tienyao)-lH-l,5Jbenzodiazepino-2,4-(3H,5H)-dion, 7- cMoro-l-metylo-5^(3Hpirydylo)-lH-l,5-benzodiazepino- -2,4-((3H,5H)-dion4 7-chloro-5-(5-chloropirydylo-(2) )- -1-metylo -1H -l,5-benzodiazepino-2,4-(3H, 5H) - dion, 7-cMoro-l-metylo-5-(4-metylopirydylo- (2)) - 1H - 1,5- benzodiazepino-2,4-(3H,5H)-dion, 7-chloro-l-metylo- -5- (4 - metylofenylo) - 1H - 1,5 - benzodiazepino - 2,4 - (3H,5H)-dion, 7- chloro-l-nietylo-5-(2-metylofenylo)- -lH-l,5-ibenzodiazepmo-2,4-(3H,5H)-dian, 7-chloro- -5-(2,3-dWumetyloffenylo)-l-metylo-lH - 1,5-benzodia- zejpino-2,4-(3H,5H)-dion, 7-chloro-5-(2,4-dwumetyio- renylo)-l-metylo-lH-l,5^benzodiazepino-2,4-(3H, 5H)- dida, 5H(2-etylofenylo)-7-diloro-lnmetylo-lH-l,5-iben- zodiaiz^pino-2,4-(3H,5H)-dion, 5-(2-metoksyfenylo)-l- ^metylo-lH-l,5-benzodiazepino-2,4-(3H,5H)-dion, 5- -(3-metoksytenylo) - l-metyilo-lH-l,5-benzodiazepino- -2,4-(3H,5H)-dion, 5-(4-metoksyfenylo)-l^metylo-lH- -l,5-benzodiazepino-2,4-(3H,5H)-dion, 7-chloro-5-(2- -chlorofenylo) - 1 - metylo -1H -1/5 - benzodiazepino- -2,4- (3H,5H)-dion, 7-chloro-5-(3-chlorofenylo)-a-me¬ tylo-lH-l,5-benzodiazepino-2,4-(3H,5H)-dion, 7-chlo- ro-5J(4 - cWorófenylo)-l-metylo-lH-l,5-benzodiazepi- no-2,4-(3H,5H)-dion, 7Hchloro-5-(2-metylo-4-cMoro- ienylo)-l-meftylo-ltt-l,5-ibenzodiazepiino-2,4-(3M, 5H)- 4 -dion, 7-chloro-l-metylo-5-(3-trójfluorometylofeny¬ lo)-lH-l,5-benzodiazepino-2,4-(3H,5H)-dion, 7-chlo- • ro-1-imetylo-5- (2-nitrofenylo)-1H-1,5-benzodiazepino- -2,4-(3H,5H)-dion, 7-chloro-5-(2-cyjanofenylo)-l-me- 5 tylo-lH-l,5-)benzodiazepino-2,4-(3H,5H)-dion, 7-chlo- ro-5-(2 - metoksykarbonylofenylo)-1-metylo -1H - 1,5- -benzodiazepino-2,4-(3H,5H)-dion, 5-(2-acetylofeny- lo)-7-cMoro-1-metylo - 1H - 1,5 - benzodiazepino - 2,4- -(3H,5H)-dion, 1 ^metylo-5-fenylo-8-trójfluorometylo- io -lHHl,5Hbenzodiazepino-2,4-(3H,5H)-dion, 8-metoksy- -l-metylo-5-fenylo - lH-l,5-benzodiazepino - 2,4 - (3H, 5H)-dion, 1,7-dwumetylo-5-fenylo-1H-1,5-benzodiaze- pino-2,4-(3H,5H)-dion, 1-metylo-5-fenylo-lH-l,5-ben- zodiazepino-2,4-(3H,5H)-dion, 7jmetoksy-l-metylo-5- 15 -fenylo-lH-ll,5-benzodiazapiino-2,4-(3H,5H)-dion, 8- -chloro-l-metylo-5-fenylo - 1H - 1,5 - benzodiazepino- -2,4-(3H,5H)-dion, l,8-dwumetylo-5-fenylo-lH-l,5- Jbenzodiazepino-2,4-(3H,5H)-dion, 6-chloro-l-metylo- -5-fenylo-lH-l,5^benzOdiazepino-2,4-(3H,5H)-dion, 7- 20 -fluoro-1-metylo - 5 - fenylo - 1H - benzodiazepino-2,4- -(3H,5H)-dion,7-bromo-l-imetylo-5-fenylo-lH^l,5-ben- zodiazepino-2,4-(3H,5H)-dion, • 7-metoksykarbonylo- -l-metylo-5-fenylo-lH-il,5 - benzodiazepino - 2,4 - (3H, 5H)-dion, 7-chloro-l,3-dwumetylo-5-fenylo-lH-l,5- 25 ^benzodiazepino-2,4-(3H,5H)-dion, 7,8-dwuchloro-l- ~metylo-5-fenylo-lH-l,5-benzodiazepino - 2,4-(3H,5H)- -dion, 7-chloro-l,3-dwumetylo-5-(2-metylofenylo) - -lH-l,5Hbenzodiazepino-2,4-(3H,5H)-dion, 7,8-dwii- chloro-1 -metylo-5-(2-pirydylo)-lH-l,5-foenzodiazepino- 30 -2,4-(3H,5H)-dion, 1-metylo-5-(2-pirydylo)-7-trój- fluorometylo-lH-l,5-benzodiazepino-2,4-(3H,5H)-dion, 1 - metylo-7-trójfluorometylo- 5 -(2 -trójfluorometylo- fenylo)-lH-l,5-benzodiazepino-2,4-(3H,5H)-dion, 1- ^metylo-7-chloro - 5 - (2 - trój£luorometylofenylo)-lH- 35 -l,5-"benzodiazepino-2,4-(3H,5H)-dion, 7-,bromo-l-me- tylo-5-(2-pirydylo)-lH-l,5-benzodiazepino-2,4-(3H,5H)- ^dion, 7-chloro-l-metylo-5-(2^pirymidynylo)-lH-l,5- -benzodiazepino-2,4- (3H,5H)-dion, 7-chloro-1-mety- lo-5-pirazynylo-lH-l,5-benzodiazepinó - 2,4 - (3H,5H)- 40 ^dion, 7-chloro-l-metylo-5-(3-pirydazynylo)-lH-l,5- benzodiazepino-2,4-(3H,5H)-dion, 7-chloro-5-(2-fury- lo)-l-metylo-lH-l,5-benzodiazepino-2,4-(3H,5H)-dion, 7-cyjano - 1 - metylo-5-fenylo-lH-l,5-benzodiazepino- -2,4-(3H,5H)-dion, l-etylo-7-chloro-5-fenylo-lH-l,5- 45 -ibenzodiazepino-2,4-(3H,5H)-dion, l-etylo-7-chloro-5- (2,3-dwumetylofenylo) - 1H - 1,5 - benzodiazepino-2,4- -(3H,5H)-dion, 1-etylo-5-fenylo-8-trójfluorometylo- -lH-ll,5-ibenzódiazepino-2,4-(3H,5H)-dion, l-etylo-8- -chloro-5-(2 - pirydylo) -1H - 1,5 - benzodiazepino-2,4- 50 -(3H,5H)-dion, l-etylo-7-chloro-5-(2-pirydylo)-lH- -l,5-ibenizodiazepino-2,4-(3H,5H)-dion, l-etylo-7-chlo- ro-5-(3-pirydylo)-lH-l,5^benzodiazepino-2,4-(3H, 5H)- -dion, 7-chloro-l-n-propylo-5-fenylo-lH-l,5-benzo- diazepino-2,4-(3H,5H)-dion, 7-chloro-l-n-propyllo-5- 5g -(2-piirydylo)-lH-l,5-ibenzodiazepino-2,4-(3H,5H)-dion, 7 - chiloro-l-izopropylo-5-fenylo-lH-l,5-benzodiazepi- no-2,4-(3H,5H)-dion, l-n-butylo-7-chloiro-5-fenylo- -lH-l,5-benzodiazepino-2,4-(3H,5H)-dion, 1-n-buty- lo-7-"chloro-5-(2-pirydylo)-lH-l,5-benzodiazepino-2,4- 69 -(3H,5H)-dion, 7-chloro-l-cykloheksylo-5-fenylo-lH- -l,5-benzodiazepino-2,4-(3H,5H)-dion, 7-chloro-l-cy- kloJhekisylo-5-(2-pirydylo) -ilH-l,5-benzodiazepino-2,4- -(3H,5H)-dion, 7-chloro-l-cyklopropylornetylo-5-fe- nylo-lH-l,5-ibenzodiazepino-2,4-(3H,5H)-dion, 7-chlo- 65 ro-l^cykloheksylometylo-5-fenylo-lH-l,5-ibenzodiaze-sfrifi 5 pino-2,4- (3H,5H)-dion, 7-chloro-l-(fMiydroksyetyilo)- -5-fenylo-lH-l,5nbenzodiazepiiK)-2,4-(3H5H)-dion, 7- -chlóro -l-(fl-hydroksyetylo) - 5 - (2-pirydylo) -lH-i,5- -foenzodifczepiino-2,4-(3H,5H)-dion, 7-chloro-l-ineto- teyetylo-5-ifenylo-lH-l,5-benzodiazepino-2,4- (3H,5H)- 5 -dion, 7-chkro-metoksyotylo-5-(2ipirydylo)-lH-l,5- -benzodiazepi!no-^,4-(3H,5H)-dioin, l-acetoksyetylo-7- Hchloro-5-fenylo -lH-I,54enzodiazepiaio-2,4-(3H, 5H)- -dion, 7^hloro-l^dwumetyloainUnoetylo-5-f6nylo-lH- -l,5^benzodiazepino-2,4-(3H,5H)-dion, 7-chloro-l- io ^wumetyloamiinoetylo-5-(2 - pirydylo)-lH-l,54enzo- diazepino-2,4-(3H,5H)-dion, l-allillo-7-chloro-5-feny- lo-lH-l,5-ibeinzodia2e(pijnio-2,4-(3H,5H)^dloiij 7-chloro- -l^^dwuifenylo -lH-l,5-ibenzodiazepino - 2,4 - (3H,5H)- -dion, 8-chloro-lHfenylo-5-(2-pirydylo)-lH-l,5^benzo- i5 diazepino-2,4-(3H,5H)^dion, 8-chloro-l-(4-chlorpfeny¬ lo)-S-fenylo-lH-l^Hbenzodiazepino^^-tSH^H) - dian, 1^(4Hmetoksyf€ffiylo)-5'-fenyilo -lH^,5-benzodi'a2ep*no- -2,4-(3H,5H)-dion, 8^chloro-l-(2,4^dwumetylofenylo)- -5-fenylo-lH-l,5-benzodiazepino-2,4-(3H,5H)-dion, 1- 20 4enzylo-7-chloro-5-fenylo -1H - 1,5 - benzodiazepdno- -2,4-(3H,5H)-dion, 7-chloro-5-fenylo-l^tienylo-lH-l,5- -Jbenzodiazepino-2,4- (3H,5H)-dion, 5-(2-ibromofenylo)- -7-chloro-lnmetylo - 1H - 1,5 - benzodiazepino-2,4-(3H, 5H)-dion, 7-tbromo-5-l(24romofenylo)-l-metylo-lH- 25 -l,5-benzodiazepino-2,4-(3H,5H)-dion, 7-bromo-5-(2- -chlorofenylo)-l-metylo-lH - 1,5 - benzodiazepino-2,4- -(3H,5H)-dion, 7-ibromo-lnmetylo-5-(2-trójfluorome- tylofenylo -1H - 1,5 - benzodiazepino-2,4-(3H,5H)^dion, 7Hbromo-5-(2 - cyjanofenylo)-1-metylo -lH-l,5-ibenizo- 30 diazepino-2,4-(3H,5H)-dion, 7-bromo-l-metylo-5-(2- -nitrofenylo) -1H - 1,5 - benzodiazepino - 2,4 - (3H,5H)- -dión, 5-(2Hbromafenylo)-l-metylo-7-trójfluoromety- lo-1H-1,5-benzodiazepino-2,4- (3H,5H)-dion, 1-imety- lo-5- (2-nitrofenylo)-7-trójfluorometylo -1H - 1,5 - ben- 35 zodiazepiino-2,4- (3H,5H)-dion, 5-(2-cyjanofenylo)-1- -metylo-7-trójfluorometylo -1H - 1,5 - benzodiazepino- -2,4-(3H,5H)-dion, 5-(2-bromofenylo)-7-fluoro-l-me- tylo-lH-l,5^benzodiazepiino-2,4-(3H,5H)-dion, 5-(2- -cyjanofenylo)-7-£luoro-lametylo -lH-l,5^benzodiaze- 40 pino-2,4-(3H,5H)-dion, 7-fluoro-l-mnetylo-5- (2-nitro- fenylo)-lH-l,5-benzodiazepino-2,4-(3H,5H)-dion, 7- -bromo-5-(2-fluorafenylo)-1 jmetylo-lH-l,5-benzodia- zepino-2,4- (3H,5H)-dion, 5-(2-fluorofenylo)-1-mety- lo-7-trójfluorometylo -lH-l,5-benzodiazepino-2,4-(3H, 45 5H)-dion, 5-(2-fluorofenylo)-7-fluoro-l-metylo-lH- -l,5-benzodiazepino-2,4-(3H,5H)-dion, 7-chloro-l-izo- propylo-5-(2-pirydylo) - 1H - 1,5 - benzodiazepino-2,4- -(3H,5H)-dion, 7-acetylo-l-metylo-5-fenylo-lH-l,5- Jbenzodiazepino-2,4-(3H,5H)-dion, 5-(2-ibromofenylo)- 5Q -7-chloro-l-metylo -1H - 1,5 - benzodiazepi'no-2,4-(3H, 5H)-dion.Ponizsze przyklady objasniaja wynalazek.Przyklad I. 7-chloro-1-metylo-5-(2-pirydylo)- -lH-l,5^benzodiazepiino-2,4-(3H,5H)-dion. 225 g (1 55 mol) 7-chloro-1nmetyio-1H-l,5nbenzodiazepino-2,4- -(3H,5H)-dionu, 147 g (1,5 imola) octanu potasu, 225 g (1,6 mola) b-lbromopirydyny, 180 g proszku miedziowego i 13*00 mil dwumetyloformamidu ogrze¬ wa sie mieszajac w temperaturze 160°C w ciagu 60 15 godzin. Mieszanine odciaga sie na goraco przez niewielka ilosc ziemi okrzemkowej i przemywa za pomoca 200 ml goracego dwumetyloformamidu.Podczas oziebiania wydziela sie krystaliczny pro¬ dukt. Mieszajac dodaje sie 2 litry pólstezonego 65 amoniaku, miesza sie dalej w ciagu 15 minut, od¬ ciaga, przemywa woda wolna od miedzi i prze- krystalizowuje sie otrzymany produkt koncowy z acetonitrylu, a nastepnie z •chlorku metylenu/eteru naftowego. Wydajnosc: 50^55% teoretycznej. Tem¬ peratura topnienia 231—233°C.Substancje wyjisciowa mozna otrzymac nastepu¬ jaco: 373 g (2 mole) 2-nitro-4-chloro-N-metyloani- liny gotuje sie z 330 g chlorku estru monoetylo- wego kwasu malonowego w 1500 ml benzenu w ciagu 2—3 godzin pod chlodnica zwrotna. Po ozie¬ bieniu, wymyciu i odparowaniu otrzymuje sie 590 g anilidu estru monoetylowego kwasu 2-nitro- -4-chloro-N-metylomalonowego. 200 g tego estru po uwodornieniu w metanodu z uzyciem niklu Raney'a przy 15 atn i w temperaturze 20°C daje 137 g ani- lidiu estru etylowego fcwasu 2-amino-4-chloro-N- -nietylomalonowego o temperaturze topnienia 114— 117°C. Do roztworu ai,5 g sodu w 7,25 litra eta¬ nolu wprowadza sie mieszajac w .temperaturze po¬ kojowej 872,2 g aminoestru. Wytraca sie sól so¬ dowa 7-chloro-l-metylo-lH-l,5-ibenzodiazepino-2,4- j(3H,5H)-dionu. Po odciagnieciu rozpuszcza sie go w 3 litrach wody, zakwasza stezonym kwasem sol¬ nym, odciaga i suszy pod próznia w temperaturze 100°C. Wydajnosc: 596 g (82,'5% teoretycznej), tem¬ peratura topnienia 215—217°C.Przyklad II. 1-metylo-5-fenylo-7-tr6jfluoro- metylo -1H - 1,5 - benzodiazepino - 2,4 - (3H, 5H)-dion. 2'57 g (1 mol) l^metylo-7-trójJ51uorometylo-lH-l,5- -benzodiazepino-2,4-<3H,6H)-dionu o temperaturze topnienia 192—194°C rozpuszcza sie 1* zawiesza w 1500 ml ibromobenzenu i po dodaniu 150 g octa¬ nu potasu i 250 g proszku miedziowego gotuje sie w ciagu 3—4 godzin pod chlodnica zwrotna. Po oziebieniu rozciencza sie za pomoca chlorku mety¬ lenu, odciaga przez saczek przykryty ziemia okrzem¬ kowa i przesacz przemywa sie 2 n lugiem sodo¬ wym oraz woda. Faze organiczna suszy sie, odcia¬ ga sie chlorek metylenu i Ibromobenzen, a pozo¬ stalosc przekrystalizowuje sie z etanolu i nastep¬ nie z chlorku metylenu/eteru izopropylowego. Wy¬ dajnosc 250 g (75% teoretycznej). Temperatura topnienia 204—206°C.Przyklad Ha. l-metylo-5-fenylo-7-tróJ!fluoro- !metylo-lH-il,5-benzodiazepino-2,4-(3H,6H)-dion. 2,6 g (=0,01 mola) l-metylo-7-trójfluorometylo^lH-l,5- -Jbenzodiazepino-2,4-(3H,5H)-dionu, 100 mg bezwod¬ nego siarczanu miedzi i i50 ml bromobenzenu go¬ tuje sie w ciagu 10 godzin pod chlodnica zwrotna.Rozciencza sie chlorkiem metylenu, przemywa roz¬ cienczonym amoniakiem, a nastepnie lugiem sodo¬ wym i woda.Wysuszona faze organiczna odparowuje sie i po¬ zostalosc wykrystalizowuje sie z eteru izopropy¬ lowego. Wydajnosc: 1,5 g = 45% teoretycznej. Tem¬ peratura topnienia 204^205°C.Przyklad III. 7-chloro-l-metylo-5-fenylo- 1H- -l,5-benzodiazepmo-2,4-{3H;5H)-dion. 245 g (1 mol) soli sodowej 7-chloro-l-metyilq-lH-l,5-ibenzodiaze- pino-2,4-(3H,5H)-dionu gotuje sie w ciagu 3^4 go¬ dzin pod chlodnica zwrotna z 1,2 1 bromobenzenu i 250 g proszku miedziowego. Dalej postepuje sie analogicznie, jak w przykladzie II. Po przefery-80 171 stalizowaniu z chlorku imetylenu/eteru izopropylo¬ wego otrzymuje sie 122 g (40*/o wydajnosci teore¬ tycznej) produktu koncowego o temperaturze top¬ nienia 182—184°*:.Przyklad IV. 7-chloro-l-metylo-!5-fenylo-lH- s -l,5-benzodiazepino-2,4-<3H,5H)-dion. 10 g 5-acety- lo-7-chloro-l-metylo -lH-l,5-benzodiazepino-2,4-(3H, 5H)-dionu, 15 g octanu potasu, 10 g proszku mie¬ dziowego i 60 ml bromobenzenu gotuje sie w ci?- gu 6 godzin pod chlodnica zwrotna. Odciaga przez io ziemie okrzemkowa, przemywa chlorkiem metyle¬ nu i odparowuje. Po przekrystalizowaniu z izopro- panolu otrzymuje sie 8 g produktu koncowego o temperaturze topnienia 180—18i20C.Przyklad V. 7-chloro-l,5-dwufenylo-lH-l,5- 15 -benzodiazepino-2,4-(8H,5H)-dion. 10 g 1-foenzoilo- -7-chloro-5-fenylo -lH-l,5-benzodiazepino - 2,4 - (3H, 5H)-dionu poddaje sie w warunkach opisanych w przykladzie IV reakcji z bromobenzenem. Po wy¬ krystalizowaniu z chlorku metylenu/eteru izopro- 20 8 pylowego otrzymuje sie 6 g produktu o tempera¬ turze topnienia 255°C.Przyklad Va. l-metylo-5-{2-nitrofenyilo)-7- -trójfluorornetylo -1,5-benzodiazepino - 2,4 - (3H, 5H)- -dion. 26 g { — 0,1 mola) l-metylo-7-trójfluorome- tylo-tl,5-benzodiazepino-2^4-(3H^H)-dionu ogrzewa sie w ciagu 1 godziny w temperaturze 150°C z 13 g octanu potasu, 1 g bezwodnego siarczanu miedzi i 3*50 g o-chlorobenzenu. Rozciencza sie chlorkiem metylenu, przemywa rozcienczonym amoniakiem, lugiem sodowym i woda, suszy sie organiczna faze i odparowuje rozpuszczalnik. Pozostalosc zadaje sie ostroznie eterem naftowym, przy czym wytraca sie produkt koncowy, który poddaje sie przekrystali¬ zowaniu z chlorku metylenu/eteru izopropylowego.Wydajnosc: 30 g = 80% teoretycznej. Temperatura topnienia 230—232CC.Analogicznie jak w opisanych sposobach poste¬ powania otrzymano dalej nastepujace zwiazki o wzorze 1, prze dtstawione w tablicy.T a b 1 i c a Przyklad 1 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 ~ 25 26 27 28. 29 30 31 32 .33 34 - 35 ' 36 37 33 39 - 40 ' 41 42 Ri 2 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 —CH2—CH3 —CH2—CH2—CH3 —CH2—CH2—CH3 Wzór 27 —(CH2)3—CH3 —CH2—CH=CH2 Wzór 28 Wzór 29 Wzór 30 Wzór 16 —CH3 —CH3 —CH3 —CH3 —CH3 R2 3 H H H H H H H H H H H H H H H H H H H H H H H H H H H ¦H H H H H H H H H H 1 R3 4 Wzór 4 Wzór 5 Wzór 6 Wzór 7 Wzór 8 Wzór 9 Wzór 10 Wzór 11 Wzór 12 Wzór 13 Wzór 14 Wzór 15 Wzór 16 Wzór 17 Wzór 18 Wzór 19 Wzór 20 Wzór 21 Wzór 22 Wzór 23 Wzór 24 Wzór 25 C€H5 C6H5 Wzór 26 CeH5 CeH5 CeH5 -C6H5 —C6H5 ' —C6H5 —C6H5 —C6H5 —C6H5 -C«H5 -C6H5 —C6H5 | R4 5 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl H H H 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 8-Cl 8-Cl H 8-CF3 8-OCH3 7-CH3 H 7-OCH3 Temperatura topnienia °C 6 209—211 173-174 164—166 216—217 225-227 203—204 201—203 200—202 190—192 179—180 205—207 126—127 175—177 222—224 191—192 227-229 202—204 192—193 206—208 209—210 183—184 205—206 227—228 197—198 177—178 143—145 158-160 203-206 231—233 244—245 243—245 192—194 130-131 162—164 194—195 170—172 132—134 |80 171 9 10 cd. tablicy 1 1 43 44 45 46 47 48 49 50 51 62 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 • 77* 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 XCVII XCVIII XCIX C CI CII CIII 1 CIV 1 j 2 —CH3 —CH3 -CH3 —CH3 —CH3 -HCH3 —CH3 —CH3 —CH2—CH3 1 —CH2—CH3 —CH3 —CH2—CgH5 1 —CH2—CH3 —CH2—CH3 OXi2^—'C-/Ji3 —(CH2)3—CH3 —C6H5 —CH3 —CH3 —CH3 —CH3 Wzór 34 Wzór 35 —CH2—CH2—OH —CH2—CH2—OCH3 Wzór 36 Wzór 27 CH3 CH3 —CH2—CH3 CH3 —CHz—CH3 CH3 CH3 —CH2—CH3 —CH2—CH2—CH3 Wzór 27 CH3 1 —CH2—CH3 Wzór 27 —CH2—CH3 CH3 Wzór 40 --CHz—CH=CH-C1 Wzór 41 Wzór 42 —CH2-^CH2—OH Wzór 42 —CH2—CH2^OCH3 —CH3—OCH3 —CH2—CH2—OC2H51 Wzór 43 —CH2—CH2—GH2—Cl 1 CH3 CH3 CH3 CH3 OH3 CH3 —(CH2)3—OH ^(CH,),—OH —CH2—CH2—OH | 1 3 H H H H H H —CH3 -CH3 H H H H H H H H H H H H H H H H H H H H H H H CH3 H H CH3 CH, CH3 H H H H H H H H H H H H H H H H H H H H H H H H H | 1 4 —C6H3 —C6H5 —C6H5 -C6H5 -C6H5 —C6H5 —C6H5 Wzór 10 Wzór 11 —C6H5 Wzór 31 —C8H5 Wzór 31 Wzór 31 Wzór 6 Wzór 31 Wzór 31 Wzór 32 Wzór 32 Wzór 311 Wzór 33 Wzór 37 C6H5 OgHs 06H5 OeH5 Wzór 31 C«H5 Wzór 36 Wzór 14 , Wzór 14 C9H5 Wzór 19 Wzór 15 Wzór 12 06H5 C6H5 Wzór 11 Wzór 17 Wzór 17 QH5 Wzór 39 06H5 CeH5 C6H5 OcH5 Wzór 17 Wzór 17 06H5 CeH5 OcH5 06H5 OeH5 Wzór 17 Wzór 3® Wzór 38 Wzór 38 Wzór 39 Wzór 39 C9H5 C*H5 CgH5 | 1 5 8-C1 8-CH3 6-C1 7-F 7-Br 7- 7-01 7-a 7-01 8-OF3 7-'CF3 7-CI 8-C1 7-Cl 7-C1 7-Cl 8-C1 7-OF3 7-Cl 7-Br 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-COCH3 7-a H 6-C1 7-a H H 7-a 7-a 7-a H 7-01 7-a 7-Br 7-Cl 7-Cl 7-a 7-a 7-a 7-a 7-a 7-a 7-a 7-a 7-01 7-a 7-CF3 7-CF3 7-Br 7-F' 7-Cl 7-CF3 7-a 7-CF3 7-CF3 | 1. 6 1 161—162 154—156 172—174 185—187 202-204 145—147 218—220 195—197 201—203 176—178 164—168 181—182 194—196 194—196 196—198 148—149 203—204 164—165 204—205 242—243 243—245 190 213—216 208—210 175—178 148—150 1 165—167 134—137 210—212 194—195 221—222 208—210 190—192 163—164 173—174 155—157 116 222—224 207—209 215-217 201—203 153—154 154—156 153—154 197—199 192—194 197—199 156—158 175—178 164—165 135—137 145 156—158 175—177 [ 194—195 [ 205—208 190—192 195—196 184—186 I 211-213 [ 157—159 153—15411 1 cv CVI CVII CVIII CIX ex CXI CXII CXIII CXIV cxv CXVI CXVII cxvin CXIX cxx C}CXI cxxn CXXIII CXXIV cxxv CXXVI CXXVII CXXVIII CXXIX cxxx CXXXI CXXXII| CXXXIII J 2 Wzór 36 Wzór 44 .C3H3 -^CH2—CH2—OH —CH2—CH3 Wzór 41 -^CH2—CH2-^OH ^CH2-CH2-0-C-CH3 -iCH2)r-OH * Wzór 28 CH3 . C2H5 n-C3H7 izo-C3H7 CH2=CH-^CH2— CH3 CH3 cri3 CH3 CH3 CH3 WTzór 46 CH3 CH3 QH5 HO^(CH2)2 Wzór 46 CH3 CH3 1 3 H H H H H H H H H H H PL PLThe right holder of the patent: CH Boehringer Sohn, Ingelheim (Federal Republic of Germany) Method for the production of new 5-aryl-1H-1,5-benzodiazepine-2,4-diones. The subject of the invention is a method for the production of new 5-aryl-1H-1,5 -ibenzodiazepine-2,4-diones of general formula I, wherein R x is a straight or branched alkyl radical of 1-4 carbon atoms, optionally substituted with a halogen atom, or a hydroxyl, alkoxy or acyloxy group, dialkylamino group with 2-4 4 carbon atoms or piperidine group linked by a nitrogen atom to an alkyl chain, or Rj is an allyl radical optionally substituted with one or two methyl groups or a chlorine atom, cyclohexyl rhodium, or cycloalkalomethyl radical, phenyl radical, or Monosubstituted or doubled methyl or methoxy group or a halogen atom, a phenylalkyl radical of 7-8 carbon atoms, R2 is a hydrogen atom or a methyl radical, R3 is a radical of the formula II, a naphthyl radical, midynyl, thienyl, or pyridyl, the latter of which may be substituted by a methyl group. or a halogen atom, R4 is a hydrogen atom, a methyl, methoxy, trifluoromethyl or nitrile group, a halogen atom or a lower acyl or alkoxycarbonyl group with 1 or 2 carbon atoms, R5 is a hydrogen atom, a methyl group, ethyl, methoxy, trifluoromethyl, nitrile or nitro, halogen or a lower acyl or alkoxycarbonyl group, and R 6 is hydrogen, methyl, ethyl or methoxy or halogen. The method of the invention is arylation or heteroarylation at the nitrogen atom of the 5 lH-1,5-tbenzodiazepine-2,4-dione of the general formula (III), where Rx, R2 and R4 are as defined above, and Y is a hydrogen atom, an alkali metal atom or an acyl group , a compound of the general formula X-R3, in which R3 is as defined above and X is a halogen atom. The acrylation is carried out in the presence of copper powder, monovalent or divalent copper salts, or mixtures thereof, or the use of an aryl halide The general formula X-R3 is in excess, or also in polar aprotic solvents, such as, for example, dimethylformamide, dimethyl sulfoxide or hexamethylphosphoramide. When using solvents, only the calculated amount of aryl halide is added. The reaction temperature depends on the starting materials used in each case and is generally 90-180 ° C. When using compounds of general formula III in which Y is a hydrogen atom or an acyl group, it is necessary to add a suitable organic base or an inorganic acid, for example an alkali metal carbonate, bicarbonate or alkoxide, or preferably an alkali metal acetate in molar amounts or in excess to bind the hydrogen chloride formed. 30 The substituted member of 1,5-benzodiazepine-2,4-ddon 8017180171 3 has been known since 1906 (R. Mayer, Annalen der Chemie, vol. 347, p. 17) and was further investigated by J. Biichi and colleagues (Helvetica Chimica Acta, vol. 39, p. 957, 1956). In this ring member, under the action of acids, it was easy to split the ring or narrow the ring to imidazole (J. Am. Chem. Soc, vol. 66, p. 1810, 1910). It has also been found that in the presence of alkali metal alcohols, there are also easily rearranged into oenzimidazolones. All the more unexpected was the discovery that this unstable ring member persists under the relatively severe conditions of the resek ^ ji-aryyl-anta presented here: - ^ i * faAypaaku ^ gfiM in relation to the general formula 1 Rj is The hydroxyalkyl group can be additionally converted to the hydroxyl group with an ethereal and burethane alkyldxyl radical in which Ri is an allyl radical optionally substituted with one or more This radical R x can also be hydrogenated in a known manner with two methyl groups or a chlorine moiety. The 1H-1,5-benzodiazepine-2,4-diones used as starting materials are new. They can be obtained, for example, by reacting an appropriately substituted 2-nitroaniline with a halide of a monoalkyl malonic acid ester, reduction of the formed 2-nitromalonic acid alkyl ester anilide and cyclization of the 2-nitromalonic acid ethyl ester anilide according to the accompanying scheme. The process can, for example, obtain the following end products: 1H-methyl-5-phenyl-7--trifluoromethyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7-chloro-1-methyl -5- (2-pyridyl) -1H-1,5- J-benzodiazepine-2,4- (3H, 5H) -dione, 7-chloro-1-methyl-5-phenyl -1H -1,5-benzodiazepine - 2,4 - (3H, 5H) - dione, 7-chloro-1-methyl-5- (1-naphthyl) -1H-1,5-benzodiazepine-2,4- (3H, 5H) - dione, 7-chloro-1-methyl-5- (2-thienya) -1H-1,5J-benzodiazepine-2,4- (3H, 5H) -dione, 7- cMoro-1-methyl-5 ^ (3H-pyridyl) -1H-1,5-benzodiazepine- -2,4 - ((3H, 5H) -dione4 7-chloro-5- (5-chloropyridyl- (2)) -1-methyl -1H -1,5-benzodiazepine -2,4- (3H, 5H) -dione, 7-cMoro-1-methyl-5- (4-methylpyridyl- (2)) - 1H - 1,5-benzodiazepine-2,4 - (3H, 5H) -dione, 7-chloro-1-methyl- -5- (4 - methylphenyl) - 1H - 1,5 - benzodiazepine - 2,4 - (3H, 5H) -dione, 7- chloro 1-non-ethyl-5- (2-methylphenyl) -1H-1,5-ibenzodiazepmo-2,4- (3H, 5H) -dio, 7-chloro -5- (2,3-dVumethylphenyl) -1- methyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7-chloro-5- (2,4-dimethylrenyl) -1-methyl-1H-1,54 benzodiazepine-2,4- (3H, 5H) - dida, 5H (2-ethylphenyl) -7-diloro-lnmethyl-1H-1,5-ibenzodiaispino-2,4- (3H, 5H) -dione , 5- (2-methoxyphenyl) -1-4 methyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 5- - (3-methoxytenyl) -1-methyl-1H-1 , 5-benzodiazepine- -2,4- (3H, 5H) -dione, 5- (4-methoxyphenyl) -1- methyl-1H- -1,5-benzodiazepine-2,4- (3H, 5H) -dione , 7-chloro-5- (2-chlorophenyl) -1-methyl -1H -1/5-benzodiazepine- -2,4- (3H, 5H) -dione, 7-chloro-5- (3-chlorophenyl) -a-methyl-lH-l, 5-benzodiazepine-2,4- (3H, 5H) -dione, 7-chloro-5J (4-c-phenyl) -1-methyl-lH-l, 5- benzodiazepine-2,4- (3H, 5H) -dione, 7H-chloro-5- (2-methyl-4-cMoroienyl) -1-mephthyl-ltt-1,5-ibenzodiazepiino-2,4- (3M , 5H) - 4-dione, 7-chloro-1-methyl-5- (3-trifluoromethylphenyl) -1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7-chloro-1 -methyl-5- (2-nitrophenyl) -1H-1,5-benzodiazepine- -2,4- (3H, 5H) -dione, 7-chloro-5- (2-cyanophenyl) -1-methyl- -1H-1,5) benzodiazepine-2,4- (3H, 5H) -dione, 7-chloro-5- (2-methoxycarbonylphenyl) -1-methyl -1H-1,5-benzodiazepine-2 , 4- (3H, 5H) -dione, 5- (2-acetylphenyl) -7-cMoro-1-methyl-1H-1,5-benzodiazepine-2,4- - (3H, 5H) -dione, 1-Methyl-5-phenyl-8-trifluoromethyl-1HHl, 5H-benzodiazepine-2,4- (3H, 5H) -dione, 8-methoxy-1-methyl-5-phenyl-1H-1,5-benzodiazepine - 2,4- (3H, 5H) -dione, 1,7-dimethyl-5-phenyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 1-methyl-5 -phenyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7-methoxy-1-methyl-5- 15-phenyl-1H-11,5-benzodiazapiino-2,4- ( 3H, 5H) -dione, 8-chloro-1-methyl-5-phenyl-1H-1,5-benzodiazepine- -2,4- (3H, 5H) -dione, 1,8-dimethyl-5-phenyl -1H-1,5-J-benzodiazepine-2,4- (3H, 5H) -dione, 6-chloro-1-methyl--5-phenyl-1H-1,5-benzodiazepine o-2,4- (3H, 5H) -dione, 7- 20-fluoro-1-methyl-5-phenyl-1H-benzodiazepine-2,4- - (3H, 5H) -dione, 7-bromo-1 -methyl-5-phenyl-1H-1, 5-benzodiazepine-2,4- (3H, 5H) -dione, • 7-methoxycarbonyl-1-methyl-5-phenyl-1H-yl, 5-benzodiazepine - 2,4- (3H, 5H) -dione, 7-chloro-1,3-dimethyl-5-phenyl-1H-1,525- benzodiazepine-2,4- (3H, 5H) -dione, 7 , 8-dichloro-1- -methyl-5-phenyl-1H-1,5-benzodiazepine - 2,4- (3H, 5H) -dione, 7-chloro-1,3-dimethyl-5- (2- methylphenyl) -1H-1,5H-benzodiazepine-2,4- (3H, 5H) -dione, 7,8-di-chloro-1-methyl-5- (2-pyridyl) -1H-1,5-foenzodiazepine- 30 -2,4- (3H, 5H) -dione, 1-methyl-5- (2-pyridyl) -7-trifluoromethyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) - dione, 1 - methyl-7-trifluoromethyl- 5 - (2-trifluoromethylphenyl) -1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 1-4-methyl-7-chloro-5 - (2 - trifluoromethylphenyl) -1H- 35 -1,5 "benzodiazepine-2,4- (3H, 5H) -dione, 7-, bromo-1-methyl-5- (2-pyridyl) -1H-1,5-benzodiazepine-2,4- (3H, 5H) -1-dione, 7-chloro-1-methyl-5- (2-pyrimidinyl) -1H-1,5-benzene odiazepine-2,4- (3H, 5H) -dione, 7-chloro-1-methyl-5-pyrazinyl-1H-1,5-benzodiazepines-2,4 - (3H, 5H) - 40-dione, 7-chloro-1-methyl-5- (3-pyridazinyl) -1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7-chloro-5- (2-furyl) - 1-methyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7-cyano-1 - methyl-5-phenyl-1H-1,5-benzodiazepine- -2,4- ( 3H, 5H) -dione, 1-ethyl-7-chloro-5-phenyl-1H-1,545-ibenzodiazepine-2,4- (3H, 5H) -dione, 1-ethyl-7-chloro-5 - (2,3-dimethylphenyl) - 1H - 1,5-benzodiazepine-2,4- - (3H, 5H) -dione, 1-ethyl-5-phenyl-8-trifluoromethyl-1H-11, 5-ibenzodiazepine -2,4- (3H, 5H) -dione, 1-ethyl-8-chloro-5- (2-pyridyl) -1H-1,5-benzodiazepine-2,4- 50 - (3H, 5H) - dione, 1-ethyl-7-chloro-5- (2-pyridyl) -1H- -1,5-ibenisodiazepine-2,4- (3H, 5H) -dione, 1-ethyl-7-chloro-5 - (3-pyridyl) -1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7-chloro-1n-propyl-5-phenyl-1H-1,5-benzodiazepine- 2,4- (3H, 5H) -dione, 7-chloro-ln-propyl-5- 5g - (2-pyridyl) -1H-1,5-ibenzodiazepine-2,4- (3H, 5H) -dione, 7 - chiloro-1-isopropyl-5- phenyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 1n-butyl-7-chloiro-5-phenyl-1H-1,5-benzodiazepine-2,4- ( 3H, 5H) -dione, 1-n-butyl-7- "chloro-5- (2-pyridyl) -1H-1,5-benzodiazepine-2,4- 69 - (3H, 5H) -dione, 7-chloro-1-cyclohexyl-5-phenyl-1H- -1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7-chloro-1-cycloJhekisyl-5- (2-pyridyl) -1H-1,5-benzodiazepine-2,4- - (3H, 5H) -dione, 7-chloro-1-cyclopropylornethyl-5-phenyl-1H-1,5-ibenzodiazepine-2,4- (3H , 5H) -dione, 7-chlor-65-l-cyclohexylmethyl-5-phenyl-lH-l, 5-ibenzodiaze-sfrifi 5-pino-2,4- (3H, 5H) -dione, 7-chloro-l - (fMiydroxyethyl) -5-phenyl-1H-1,5-n-benzodiazepiaK) -2,4- (3H5H) -dione, 7- -chloro-1- (f-hydroxyethyl) - 5 - (2-pyridyl) -1H- and, 5--benzodiflaginino-2,4- (3H, 5H) -dione, 7-chloro-1-inetothyethyl-5-phenyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) - 5-dione, 7-chro-methoxyotyl-5- (2-pyridyl) -1H-1,5-benzodiazepiol - ^, 4- (3H, 5H) -dioin, 1-acetoxyethyl-7- H-chloro-5- phenyl-1H-I, 54-benzodiazepiaio-2,4- (3H, 5H) -dione, 7-chloro-1-dimethylamino-ethyl-5-f 6-yl-1H- -1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7-chloro-1-10- dimethylaminoethyl-5- (2-pyridyl) -1H-1,54-benzodiazepine-2 , 4- (3H, 5H) -dione, l-alliloyl-7-chloro-5-phenyl-lH-l, 5-ibeinzodia2e (pyno-2,4- (3H, 5H) dloiij 7-chloro -1 ^^ diiphenyl -1H-1,5-ibenzodiazepine - 2,4 - (3H, 5H) -dione, 8-chloro-1Hphenyl-5- (2-pyridyl) -1H-1,5-benzo-i5 diazepine-2,4- (3H, 5H) ^ dione, 8-chloro-1- (4-chlorphenyl) -S-phenyl-1H-1H-benzodiazepine ^^ - tSH ^ H) - dian, 1 ^ ( 4H-methoxif € fphyl) -5'-phenylyl-1H ^, 5-benzodi'a 2ep * no- -2,4- (3H, 5H) -dione, 8'-chloro-1- (2.4 ^ dimethylphenyl) - -5 -phenyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 1-20-4enzyl-7-chloro-5-phenyl -1H-1,5-benzodiazepine- -2,4- ( 3H, 5H) -dione, 7-chloro-5-phenyl-l-thienyl-lH-l, 5--ibenzodiazepine-2,4- (3H, 5H) -dione, 5- (2-ibromophenyl) -7 -chloro-lnmethyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7-tbromo-5-l (24romophenyl) -1-methyl-1H- 25 -1,5-benzodiazepine- 2,4- (3H, 5H) -dione, 7-bromo-5- (2-chlorophenyl) -1-methyl-1H - 1,5-benzodiazepine-2,4- - (3H, 5H ) -dione, 7-ibromo-l-methyl-5- (2-trifluoromethylphenyl) -1H - 1,5-benzodiazepine-2,4- (3H, 5H) ^ dione, 7H-bromo-5- (2 - cyanophenyl) -1 -methyl-1H-1,5-ibeniso-diazepine-2,4- (3H, 5H) -dione, 7-bromo-1-methyl-5- (2-nitrophenyl) -1H -1,5-benzodiazepine - 2,4 - (3H, 5H) -dión, 5- (2H-bromaphenyl) -1-methyl-7-trifluoromethyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 1-Methyl-5- (2-nitrophenyl) -7-trifluoromethyl -1H - 1,5-benzodiazepiino-2,4- (3H, 5H) -dione, 5- (2-cyanophenyl) -1 - -methyl-7-trifluoromethyl -1H - 1,5-benzodiazepine- -2,4- (3H, 5H) -dione, 5- (2-bromophenyl) -7-fluoro-1-methyl-1H-1 , 5'-benzodiazepiino-2,4- (3H, 5H) -dione, 5- (2-cyanophenyl) -7-Lluoro-methyl-1H-1,5'benzodiaze-40pino-2,4- (3H , 5H) -dione, 7-fluoro-1-methyl-5- (2-nitrophenyl) -1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7--bromo-5 - (2-fluoraphenyl) -1-methyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 5- (2-fluorophenyl) -1-methyl-7-trifluoromethyl - 1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 5- (2-fluorophenyl) -7-fluoro-1-methyl-1H- -1,5-benzodiazepine-2,4- (3H, 5H) -dione, 7-chloro-1-isopropyl-5- (2-pyridyl) -1H- 1,5-benzodiazepine-2,4- - (3H, 5H) -dione, 7-acetyl-1-methyl-5-phenyl-1H-1,5-J-benzodiazepine-2,4- (3H, 5H) -dione , 5- (2-ibromophenyl) -5Q -7-chloro-1-methyl -1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione The following examples illustrate the invention. Example I. 7 -chloro-1-methyl-5- (2-pyridyl) -1H-1,5-benzodiazepiino-2,4- (3H, 5H) -dione. 225 g (1 55 mol) 7-chloro-1-methyl-1H-1,5-benzodiazepine-2,4- - (3H, 5H) -dione, 147 g (1.5 mol) potassium acetate, 225 g (1.6 mol) ) b-bromopyridine, 180 g of copper powder and 13.00 ml of dimethylformamide are heated with stirring at 160 ° C. for 60 hours. The mixture is drawn hot through a little diatomaceous earth and washed with 200 ml of hot dimethylformamide. On cooling, a crystalline product is separated. While stirring, 2 liters of semi-concentrated ammonia are added, stirred for a further 15 minutes, strained, washed with copper-free water and the resulting end product recrystallized from acetonitrile and then from methylene chloride / petroleum ether. Yield: 50 ^ 55% of theoretical. Melting point 231-233 ° C. The starting material can be obtained as follows: 373 g (2 moles) of 2-nitro-4-chloro-N-methylaniline are boiled with 330 g of malonic acid monoethyl ester chloride in 1500 ml of benzene within 2-3 hours under a reflux condenser. After cooling, washing and evaporation, 590 g of 2-nitro-4-chloro-N-methylmalonic acid monoethyl ester anilide are obtained. 200 g of this ester, after hydrogenation in methane with Raney nickel at 15 atn and 20 ° C, yields 137 g of 2-amino-4-chloro-N-nietylmalonic acid ethyl ester anelide, mp 114-117 ° C C. 872.2 g of the aminoester are added to a solution of 1.5 g of sodium in 7.25 liters of ethanol with stirring at room temperature. The sodium salt of the 7-chloro-1-methyl-1H-1,5-ibenzodiazepine-2,4-i (3H, 5H) -dione is precipitated. After extraction, it is dissolved in 3 liters of water, acidified with concentrated hydrochloric acid, drained and dried under vacuum at 100 ° C. Yield: 596 g (82.5% of theory), mp 215-217 ° C. Example II. 1-methyl-5-phenyl-7-tr6-fluoro-methyl -1H-1,5-benzodiazepine-2,4 - (3H, 5H) -dione. 2.57 g (1 mole) of l, methyl-7-tri-uoromethyl-lH-l, 5-benzodiazepine-2,4- <3H, 6H) -dione, m.p. 192-194 ° C is dissolved 1 * suspended in 1500 ml of ibromobenzene and after adding 150 g of potassium acetate and 250 g of copper powder are boiled for 3-4 hours under reflux. After cooling, it is diluted with methylene chloride, sucked through a filter covered with diatomaceous earth, and the filtrate is washed with 2 N sodium hydroxide solution and water. The organic phase is dried, methylene chloride and i-bromobenzene are separated off and the residue is recrystallized from ethanol and then from methylene chloride / isopropyl ether. Yield 250 g (75% of theory). Melting point 204-206 ° C. Example Ha. 1-methyl-5-phenyl-7-tri-fluoro-! methyl-1H-yl, 5-benzodiazepine-2,4- (3H, 6H) -dione. 2.6 g (= 0.01 mol) of 1-methyl-7-trifluoromethyl-1H-1,5-J-benzodiazepine-2,4- (3H, 5H) -dione, 100 mg of anhydrous copper sulphate and 50 ml The bromobenzene is boiled for 10 hours under reflux. It is diluted with methylene chloride, washed with dilute ammonia, then with sodium hydroxide and water. The dried organic phase is evaporated and the residue is crystallized from isopropyl ether. Yield: 1.5 g = 45% of theoretical. Melting point 204 ° 205 ° C. Example III. 7-chloro-1-methyl-5-phenyl-1H- -1,5-benzodiazepmo-2,4- {3H; 5H) -dione. 245 g (1 mole) of the sodium salt of 7-chloro-1-methyl-1H-1,5-ibenzodiazepine-2,4- (3H, 5H) -dione are boiled for 3 to 4 hours under reflux. with 1.2 l of bromobenzene and 250 g of copper powder. The next steps are the same as in example II. After conversion from imethylene chloride / isopropyl ether, 122 g (40% theoretical) of end product were obtained, mp 182-184%. EXAMPLE IV. 7-chloro-l-methyl-? 5-phenyl-lH-s-l,5-benzodiazepine-2,4- < 3H, 5H) -dione. 10 g of 5-acetyl-7-chloro-1-methyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione, 15 g of potassium acetate, 10 g of copper powder and 60 ml bromobenzene is boiled for 6 hours under a reflux condenser. It is strained through and through diatomaceous earth, washed with methylene chloride and evaporated. After recrystallization from isopropanol, 8 g of the final product are obtained, m.p. 180-18 ° C. Example V. 7-chloro-1,5-diphenyl-1H-1,5-benzodiazepine-2,4- (8H, 5H). ) -dion. 10 g of 1-foenzoyl -7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4- (3H, 5H) -dione are reacted with bromobenzene under the conditions described in example IV. After recrystallization from methylene chloride / isopropyl ether, 6 g of product are obtained, m.p. 255 ° C. 1-methyl-5- {2-nitrophenyl) -7-trifluoromethyl -1,5-benzodiazepine-2,4 - (3H, 5H) -dione. 26 g {-0.1 mol) 1-methyl-7-trifluoromethyl-t1, 5-benzodiazepine-2 ^ 4- (3H ^ H) -dione are heated for 1 hour at 150 ° C with 13 g potassium acetate, 1 g anhydrous copper sulfate and 3 * 50 g o-chlorobenzene. Dilute with methylene chloride, wash with dilute ammonia, sodium hydroxide and water, dry the organic phase and evaporate the solvent. The residue is carefully treated with petroleum ether, the final product precipitates and is recrystallized from methylene chloride / isopropyl ether. Yield: 30 g = 80% of theory. Melting point 230-232 ° C. The following compounds of formula 1, shown in the table below, were obtained analogously to the procedures described below: Example 1 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 ~ 25 26 27 28.29 30 31 32 .33 34 - 35 '36 37 33 39 - 40' 41 42 Ri 2 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 —CH2 — CH3 —CH2 — CH2 — CH3 —CH2 — CH2 — CH3 Formula 27 - (CH2) 3 — CH3 —CH2 — CH = CH2 Formula 28 Formula 29 Formula 30 —CH3 —CH3 —CH3 —CH3 —CH3 R2 3 HHHHHHHHHHHHHHHHHHHHH HHHHHH ¦HHHHHHHHHH 1 R3 4 Pattern 4 Pattern 5 Pattern 6 Pattern 7 Pattern 8 Pattern 9 Pattern 10 Pattern 11 Pattern 12 Pattern 13 Pattern 14 Pattern 15 Pattern 16 Pattern 17 Pattern 18 Pattern 19 Pattern 20 Pattern 21 Pattern 22 Pattern 23 Pattern 24 Formula 25 C € H5 C6H5 Formula 26 CeH5 CeH5 CeH5 -C6H5 —C6H5 "—C6H5 —C6H5 —C6H5 —C6H5 -C" H5 -C6H5 —C6H5 | R4 5 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl HHH 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7- Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 8-Cl 8-Cl H 8-CF3 8-OCH3 7-CH3 H 7- OCH3 Melting point ° C 6 209-211 173-174 164-166 216-217 225-227 203-204 201-203 200—202 190-192 179-180 205-207 126-127 175—177 222-224 191— 192 227-229 202—204 192—193 206—208 209—210 183—184 205—206 227—228 197—198 177—178 143—145 158-160 203-206 231—233 244—245 243—245 192 —194 130-131 162—164 194—195 170—172 132—134 | 80 171 9 10 cont. table 1 1 43 44 45 46 47 48 49 50 51 62 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 • 77 * 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 XCVII XCVIII XCIX C CI CII CIII 1 CIV 1 j 2 —CH3 —CH3 -CH3 —CH3 —CH3 -HCH3 —CH3 —CH3 —CH2 — CH3 1 —CH2 — CH3 —CH3 —CH2 —CgH5 1 —CH2 — CH3 —CH2 — CH3 OXi2 ^ - 'C- / Ji3 - (CH2) 3 — CH3 —C6H5 —CH3 —CH3 —CH3 —CH3 Formula 34 —CH2 — CH2 — OH —CH2 — CH2 —OCH3 Formula 36 Formula 27 CH3 CH3 —CH2 — CH3 CH3 —CHz — CH3 CH3 CH3 —CH2 — CH3 —CH2 — CH2 — CH3 Formula 27 CH3 1 —CH2 — CH3 Formula 27 —CH2 — CH3 CH3 Formula 40 --CHz— CH = CH-C1 Formula 41 Formula 42 —CH2- ^ CH2 — OH Formula 42 —CH2 — CH2 ^ OCH3 —CH3 — OCH3 —CH2 — CH2 — OC2H51 Formula 43 —CH2 — CH2 — GH2 — Cl 1 CH3 CH3 CH3 CH3 OH3 CH3 - (CH2) 3-OH3 (CH1), - OH -CH2-CH2-OH | 1 3 H H H H H H —CH3 -CH3 H H H H H H H H H H H H H H H H H H H H H H H H CH3 H H CH3 CH, CH3 H H H H H H H H H H H H H H H H H H H H H H H H H | 1 4 —C6H3 —C6H5 —C6H5 -C6H5 -C6H5 —C6H5 —C6H5 Formula 10 Formula 11 —C6H5 Formula 31 —C8H5 Formula 31 Formula 31 Formula 6 Formula 31 Formula 31 Formula 32 Formula 311 Formula 33 Formula 37 C6H5 OgHs 06H5 OeH5 Pattern 31 C «H5 Pattern 36 Pattern 14, Pattern 14 C9H5 Pattern 19 Pattern 15 Pattern 12 06H5 C6H5 Pattern 11 Pattern 17 Pattern 17 QH5 Pattern 39 06H5 CeH5 C6H5 OcH5 Pattern 17 Pattern 17 06H5 CeH5 OcH5 06H5 OeH5 Pattern 17 Pattern 3® Pattern 38 Formula 38 Formula 39 Formula 39 C9H5 C * H5 CgH5 | 1 5 8-C1 8-CH3 6-C1 7-F 7-Br 7- 7-01 7-a 7-01 8-OF3 7-'CF3 7-CI 8-C1 7-Cl 7-C1 7-Cl 8-C1 7-OF3 7-Cl 7-Br 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-Cl 7-COCH3 7-a H 6-C1 7-a HH 7-a 7-a 7-a H 7-01 7-a 7-Br 7-Cl 7-Cl 7-a 7-a 7-a 7-a 7-a 7-a 7-a 7-a 7-01 7 -a 7-CF3 7-CF3 7-Br 7-F '7-Cl 7-CF3 7-a 7-CF3 7-CF3 | 1. 6 1 161—162 154—156 172—174 185—187 202-204 145—147 218—220 195—197 201—203 176—178 164—168 181—182 194—196 194—196 196—198 148 —149 203—204 164—165 204—205 242—243 243—245 190 213—216 208—210 175—178 148—150 1 165—167 134—137 210—212 194—195 221—222 208—210 190 —192 163—164 173—174 155—157 116 222—224 207—209 215-217 201—203 153—154 154—156 153—154 197—199 192—194 197—199 156—158 175—178 164— 165 135—137 145 156—158 175—177 [194—195 [205—208 190—192 195—196 184—186 I 211-213 [157—159 153—15411 1 cv CVI CVII CVIII CIX ex CXI CXII CXIII CXIV cxv CXVI CXVII cxvin CXIX cxx C} CXI cxxn CXXIII CXXIV cxxv CXXVI CXXVII CXXVIII CXXIX cxxx CXXXI CXXXII | CXXXIII J 2 Formula 36 Formula 44 .C3H3 - ^ CH2 — CH2 — OH —CH2 — CH3 Formula 41 - ^ CH2 — CH2- ^ OH ^ CH2-CH2-0-C-CH3 -iCH2) r-OH * Formula 28 CH3 . C2H5 n-C3H7 iso-C3H7 CH2 = CH- ^ CH2— CH3 CH3 cri3 CH3 CH3 CH3 WT Formula 46 CH3 CH3 QH5 HO ^ (CH2) 2 Formula 46 CH3 CH3 1 3 H H H H H H H H H H H PL PL