IL30993A - 3-indolinyl-2-amino-propionitriles and their preparation - Google Patents

Description

and their The present invention concerns a new process for the produc ion nitriles and the new compounds obtained by this The process according to the to the new iles of formul wherein represents an alkyl group of 1 to 5 carbon atoms the benzyl or the allyl R2 represents an alkyl of 1 to 5 carbon the benzyl or the allyl or and together with the adjacent nitrogen atom represent a to saturated heterocyclic radical which can also contain further hetero atoms as ring R represents lower or an a cyl radical d from a lower phatic Rg and independently of each other represent a lower alkyl or alkoxy halogen or the i comprises reac wherein to R have the meanings given in formula with tri and with a secondary amine of formula 3 wherein and have the meanings given in formula The action is carried out with the components being used in ably approximately equimolar amounts of a temperature between 0 and preferably of from about 10 optionally in a solvent or diluent inert to the above reaction partners at th above temperature The compounds of formula are obtained in very satis factory The substituents and comprise ajgroup of tuents which impart to the amine formula III a basicity favourable for the reaction with the other The new compounds can as a lower alkyl substituent the or hexyl B to saturated heterocyclic radicals in the above definition of and are morpholine and always hromine and iodine are In the production of compounds of formula I wherein one of the symbols to represents the nitro group and sents the yields are somewhat Such compounds are also in the yields by previous acylation of the corresponding ni satins by methods known per se and sequent splitting off of the acyl The compounds are stalline after re crystal sati on they are in crystalline they dissolve well and are stable in the usual organic For isatins of formula reactions according to the process of the invention have not been described the In attempts to react isatin with ace taldehyde with an comprising primary and secondary amines as well as and with an aqueous we obtained a series of condensation products which were difficult to It is therefore surprising that starting with lactonitrile and a secondary amine it is possible to attain the according to the The isatins of formula II used as starting materials for the process according to the invention are known compounds or can be produced in a simple way from known Giovannini et al acta and or carbamoyl isatins are not The former can be produced by acylation of ponding Giovannini et al and the latter from the corresponding esters Giovannini et by reaction with ry or secondary amines or by partial saponification of a ponding Other isatins of formula II which have not been described can be produced by methods The of the formula I wherein is not hydrogen can also be obtained by according to the an isatin of formula II wherein is hydrogen with lactonitrile and a secondary amine of formula III and exchanging hydrogen in the reaction product obtained for another radical having the meaning of In this alkylating agents such as alkyl sulphates toluene sulphonic acid also acylating agents such as halides of aliphatic or aromatic carboxylic are The following examples further illustrate the mance of the process according to the Following this there is a list of compounds of formula I produced by the process according to the The temperatures are given in degrees Centigrade Example 1 161 g of satin are suspended in 1 of 75 g of lactonitrile and 200 g of di benzylamine are added and the whole is stirred for 43 hours at After cooling to the precipitate is collected and recrystallised from ethyl The 1 3 le so obtained melts at The yield is Example 2 g of thyli satin are suspended in 200 ml of 15 g of lactonitrile and 22 g of are added and the reaction mixture is stirred for 13 hours at room The precipitate is dried and crystallised from ethyl The so obtained melts at The yield is 34 The ndo li nitriles summarised in the following Table are obtained by the method described in the above examples using equimolar of the corresponding lactonitrile and secondary a b l e insufficientOCRQuality

Claims (4)

1. Process for the production of 3-indolinyl-2-amino-propionitriles of the general irmula I wherein R^ represents an alkyl group of 1 to 5 carbon atoms, the "benzyl or the allyl group, Rg represents an alkyl group of 1 to 5 carbon atoms, the benzyl or the allyl group, or R^ and R^ together with the adjacent nitrogen atom represent a 5-to 7-raembered saturated heterocyclic radical which can also contain further hetero atoms as ring members, ^ represents hydrogen, lower alkyl, benzyl, di-lower-alkylamino-methyl, piperidino-methyl, or an acyl radical derived from a lower aliphatic carboxylic acid, ^, R^, Rg and ^ independently of each other represent hydrogen, a lower alkyl or alkoxy radical, halogen or the nitro group characterised by reacting an isatin of the formula II wherein to ^ have the meaning given above, with lactonitrile (CH^-CHOH-OT) and with a secondary amine of the formula III (III) 30993/2 - 12 - wherein R^,;. and have the meaning given above, the reaction being carried out at a temperature between 0 and 50°G, preferably between 10 and 30°C, optionally in a solvent or diluent which is inert to the above reactants at the aforementioned temperature range.

2. O Process according to Claim 1 , wherein virtually equimolar amounts of the reaction components are reacted with each other.

3. ■}-'(} · -Hydroxy-indolin-2 ' -on-3 ' -yl ) -2-amino-propio- nitriles of the formula I wherein R^ to have the same meanings as in Claim 1 ,

4. 3- ( 3'-Hydroxy-indolin-r2,-on-3,-yl) -2-amino-propio- nitriles of formula I in Claim 1 , wherein R^ and are each a benzyl radical. For the Applicants D&.HEINHOLD QOHN AJJD PAR NERS By: ND:BH