L,4-benzodiazepin-5-one

Azido-l, 4-benzodiazepin-2-ones 43 arc obtained from 1,4-benzodiazepin-2-ones by treatment with potassium bis(trimethylsilyl)amide, followed by 2,4,6-triisopropylbenzencsulfonyl azide. The azides are reduced to the corresponding amino compounds 44 by the action of triphenyl-phosphane in aqueous tetrahydrofuran. No further details were reported.429... 

CN 7-chloro-l-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-l,3-dihydro-2H-l,4-benzodiazepin-2-one... 

CN 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-1 -methyl-2f/-l, 4-benzodiazepin-2-one... 

Microwave-promoted reactions continue to extend their reach in heterocyclic synthesis. Regioselective N4-aminoethylation of the l,4-benzodiazepin-2-one 94 was observed under microwave conditions in DMF/K2C03 to afford, for example, 96a and 96b in 64% and 67% yield respectively (Table 4). In contrast, the thermal reaction at 80 °C in DMF with K.2CC)3 as base gave the Nl-aminoethylation products (95a, 65%) and (95b, 76%). These results were... 

Diazepam From a chemical point of view, diazepam, 7-chloro-l,3-dihydro-l-methyl-5-phenyl-2H-l,4-benzodiazepin-2-one (5.1.2), is the most simple of all of the examined derivatives of l,4-benzodiazepin-2-ones. Various ways for the synthesis of diazepam from 2-amino-5-chlorobenzophenone have been proposed. The first two ways consist of the direct cyclocondensation of 2-amino-5-chlorobenzophenone or 2-methylamino-5-chlorobenzophenone with the ethyl ester of glycine hydrochloride. The amide nitrogen atom of the obtained 7-chloro-l,3-dihydro-5-phenyl-2H-l,4-benzodiazepin-2-one (5.1.1), is methylated by dimethylsulfate, which leads to the formation of diazepam (5.1.2). 

In the second, simpler scheme, synthesis begins with 7-chloro-5-phenyl-2,3-dihydro-l//-l,4-benzodiazepin-2-one (5.1.1), which is alkylated by cyclopropylmethylbromide in the presence of sodium amide into prazepam (5.1.11) [11,12]. 

Halazepam Halazepam, 7-chloro-1 -(2, 2, 2 -trifluoro-1 -ethy 1)-l,3-dihydro-5-pheny 1-2//-l,4-benzodiazepin-2-one (5.1.19), also differs from diazepam in that it has a substituent on the nitrogen atom in the first position of the benzodiazepine system, which in this case is represented by the 2, 2, 2 -trifluoroethyl group. It can be made by any of the diagrams described above [13,14],... 

Formation of this bond as an amide linkage has been much used but most often as the first or last step in a type ac synthesis of l,4-benzodiazepin-2-ones, e.g. (151) or (154). Monocyclic 1,4-diazepines have been prepared by the cyclization of a,o>-aminoesters... 

Reactions of this type provide one of the major routes to the commercially important l,4-benzodiazepin-2-one system (156) via the reaction of substituted o-aminobenzoph-enones (155) with amino acid esters (68CRV747, p. 756). This synthesis allows the easy preparation of 3-substituted products by the use of readily available a-substituted amino acids, e.g. the CNS active Tranxene (156 Y = C1, Ar = Ph, R1 = CC>2H) by using aminomalonic ester. Similar reactions have been carried out using other three-atom components, e.g. 2-bromoethylamine (77MIP51800) and ketenimines (77JHC99). 

The fusion of rings on to side d has usually been achieved via adaptations of known reactions of the imine, nitrone or imino chloride functions. Some examples are given for the l,4-benzodiazepin-2-one (202). 

The alkaline hydrolysis of the l,4-benzodiazepin-2-one (236) and its 4-oxide resulted in ring opening via amide cleavage. Similarly treatment with methylamine gave (246) which proved to be a useful intermediate in the synthesis of the 3-carboxamide (247). 

Mild alkaline hydrolysis of (186 R = Me) gave the l,4-benzodiazepin-2-one 4-oxide. Grignard reagents react with the nitrone (152 R = R1 = H) and similar compounds to give the 4-hydroxy-5-phenyl derivative (77ACS(B)70l). 

One of the commercially important routes to l,4-benzodiazepin-2-ones (361) from 2-aminobenzo-phenones (358) involves the reaction of (359) with ammonia. Intermediate (360) can be isolated. 

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