Preparation of chiral 1,4-benzodiazepin-2-one-derivatives by reaction of (s)-.alpha.-amino acid chloride hydrochlorides etc.
AssigneeCRC Compagnia di Ricerca Chimica S.A.
InventorsFranjo Kajfez, Vitomir Sunjic
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Abstract
A process is disclosed for preparing optically active 1,4-diazepine-2-ones by reacting an acid chloride-hydrochloride of an optically active .alpha.-amino acid with a substituted o-amino benzophenone, to form an intermediate product and subsequently cyclizing the intermediate product to form the desired 1,4-diazepine-2-one. The process is carried out in inert organic or aqueous-organic solvents. The process eliminates the need for using .alpha.-amino acids having bound to the amino group a protective group which must be removed before cyclization.
Claims9
A process preparing optically active 1,4-benzodiazepin-2-ones with (S)-configuration in the 3-position having the formula I ##STR5## wherein R.sub.1 is a hydrogen atom, or a halogen atom, R.sub.2 is an n- or iso- lower alkyl radical with at most 4 carbon atoms, a benzyl, p-hydroxybenzyl, or 3'-methyleneindolyl group, R.sub.3 is a hydrogen atom or a halogen atom, comprising the steps of (a) reacting, in an inert solvent selected from methylene chloride and tetrahydrofuran at about room temperature, a compound of the formula II ##STR6## wherein R.sub.1 and R.sub.3 have the same significance as in Formula I with a compound of the formula III in the (S)-configuration ##STR7## in which R.sub.2 has the same significance as in Formula I and Hal is a halogen atom, whereby an intermediate compound of the formula IV in the (S)-configuration is formed, and ##STR8## (b) cyclizing said intermediate compound in an inert solvent selected from the group consisting of a homogeneous mixture of water and an organic solvent and non-polar organic solvents, at a temperature of up to about 40.degree. C whereby the compound of Formula I in the (S)-configuration is formed.
Dependencies are inferred from the claim text.