IL24802A - Dibenzocycloheptenes,their manufacture and pharmaceutical preparations containing them - Google Patents

Description

wherein definition of X and the significance of the dotted line are as previously As is evident the above reaction the unsubstituted hyl derivative is obtained by reduction of the corresponding substituted 1 hydride in the presence of a suitable inert 2 organic solvent such as tetrahydro ether or 3 other solvent conventionally employed with lithium Preferably this reduction is carried out in the presence of aluminum chloride and an ether compatible with aluminum chloride as a The temperature at which the reduction is carried out 8 is not critical but it is preferred to employ elevated 9 temperatures up to about The resulting aminomethvl 10 derivative readily employing conventional The 12 derivative is prepared by formylation of 13 aminomethyl compound employing conventional conditions and such as formic acid or esters for this The resulting for mido e h 1 1 derivative can be recovered in conventional 17 The derivative is readily 13 prepared by the treatment of the primary amine 19 compound formaldehyde and formic acid in 20 accordance h the known modification of the Leuckart Recovery of the di ethylami 22 methyl derivative is accomplished in conventional 23 The minomethyl compounds may be prepared by either reduction of the methyl derivative or by of 26 the dimethylamino derivative Reduction 1 of III can be effected in 2 known such as by treatment with cyanogen bromide 3 followed by hydrolysis of the intermediate or by treatment with a followed by 5 hydrolysis of the urethane In each 6 instance the desired compound can be recovered 7 ing conventional 8 The starting the 9 or its 0 either of which may be further substituted 1 by X as defined may be prepared by reacting 2 a substituted dibenzocycloheptene with 3 cuprous cyanide in a suitable anhydrous solvent and at a suitable preferably in the range of to 6 The following examples are illustrative 7 but not limitative of the Example 1 8 9 A solution of anhydrous aluminum chloride 0 in of anhydrous ether 1 is added dropwise to a solution of lithium aluminum 2 hydride in of absolute 3 ether while An atmosphere of nitrogen is maintained in the apparatus and all vents are with drying tubes during the A in 2 of absolute is added dropwise stirring warming of this solution be necessary to prevent precipitation of the The reaction is stirred at for 1 hour after the addition is 35 then is added Dilute sulfuric acid is causing precipitation of a white The solid is suspended in water and the mixture rendered strongly alkaline with sodium hydroxide The filtrate also is rendered strongly alkaline and both mixturesa containing suspended solids are extracted separately with Distillation of the ether from the combined extracts leaves a solid weighing Recrystallization from gives of An analytical melts at for 2 Following substantially the same procedure as Example 1 and replacing the cycloheptene of Example 1 with listed below there are obtained the products enumerated Products 2 3 ε cycloheptene cycloheptene 7 cycloheptene cycloheptene 3 1 9 10 cycloheptene cycloheptene 11 12 13 cycloheptene 15 dibenzo cycloheptene cycloheptene 16 17 18 cycloheptene cycloheptene 19 20 dibenzo cycloheptene dibenso cycloheptene 21 22 dibenzo 23 3 25 enzo cycloheptene 26 27 and methyl 200 are 23 heated to for l6 hours in an 29 The solution is evaporated to dryness on a 30 film evaporator under reduced The residue 31 is dissolved in the solution extracted 32 with dilute hydrochloric then with water and 33 dried over anhydrous The benzene cycloheptene 19 cycloheptene 22 cycloheptene 23 cycloheptene cycloheptene 25 26 cyclohep tone cycloheptene 1 sodium 1 and 3 then are added to the vigorously stirred reaction After standing several the reaction is filtered and the solid washed several by suspension in The combined filtrates and washings are evaporated 19 on a evaporator under reduced the 20 pale yellow oily residue is dissolved in dilute chloric the solution extracted with ether to remove rendered alkaline 23 the product extracted with After washing with water and over anhydrous sodium ether is evaporated on a film evaporator under 26 reduced The yellow oily residue weighs 27 A portion is dissolved in isopropyl of maleic acid in of isopropyl alcohol is T e d salt of the product separates out in It at 16 after further recrys isopropyl alcohol and drying in vacuo over phosphorus Ca for 6 Following substantially tho same procedure of Example and replacing the cycloheptene of with the enumerated in Example the following products are cycloheptene cycloheptene dibenzo cycloheptene cycloheptene cycloheptene cycloheptene cycloheptene cycloheptene e is continued for 8 After cooling to room 3 of hydrochloric acid is added and the mixture is evaporated to dryness on a film evaporator under reduced The and the solution is hydroxide The product is extracted into the extract is washed with water and dried over anhydrous sodium Evaporation of the benzene and drying the residue in a film evaporator under reduced pressure gives of the yellow oily The dissolved in 10 of isopropyl alcohol and a solution of aleic acid in 3 of isopropyl alcohol is The hydrogen male te separates and a ter the addition of it is collected and from isopropyl The product melts at for Q 1 8 2 Following substantially procedure 3 of 7 and replacing the dibenzo cycloheptene of Example 7 2 6 products 7 cycloheptene 9 10 dibenzo cyclohepteno 11 12 13 cycloheptene 16 cycloheptene 21 22 cycloheptene insufficientOCRQuality

Claims (1)

1. particularly described and ascertained the nature of our said invention and in what manner the same is to be we declare that ia 1 A process for the preparation compounds of the X is selected from the group consisting of lowe trifluoro ethyl lower lower lower to and dilower sulfamoyl whic the steps of reducing a of the wherein X is as with li hydride in the presence of an inert solvent to form the corresponding a treating the product of step with formaldehyde and acid to the corresponding derivative and the product of step 2 A process for the preparation of of the wherein X is selected the group consisting of lower lower and dilower which the steps of reducing a of the formulae wherein X is as with lithium hydride in the presence of an inert organic solvent to form the corresponding the product of step the corresponding derivative and reducing the product of step with hydride in the presence of an inert organic solven A process for the of of the formulae wherein X is selected from the group consisting of lower lower lower lower and dilower alkylsul which comprises the steps of reducing a compound of the Wherein is as lit hydride the presence of an inert solvent to corresponding derivatives and the product of step A for the preparation of coajpounda of the formulae herein X is selected from the group consisting of l treating the product of step with formaldehyde and formic A pharmaceutical composition comprising a pharmaceutic carrier and a compound selected from the group consisting of compounds of the formulae s A selected the of compounds of the aanndd ssaallttss tthheerreeooff XX iiss sseelleecctteedd ffrroomm tthhee ggrroouupp ccoonnssiissttiinngg ooff lloovveerr hhyyii lloowweerr lloowweerr aallkkyyllssuullfoonnyyll lloowweerr ee aanndd d diilloowweerr aallllccyyll ssuullf RR iiss sseelleecctteedd tthhee ggrroouupp ccoonnssii ssttiinngg ooff hhyyddrrooggeenn aanndd tthhyyll aanndd iiss sseelleecctteedd tthhee ggrroouupp ccoonnssiissttiinngg ooff hhyyddrrooggeenn mmeetthhyyll 7 7 ccyycclloohheepptteennee 8 8 ccyycclloohheepptteennss 9 10 ibenzo irn ethyl o ri fluor thyl 1 Cycloheptene thyl thyl sul f thyl Λ selected from the group consisting of compounds of the wherein X is selected the group consisting of lower lower lower lower alkylmercapto and alkyl sulf Dated this 14th day of insufficientOCRQuality