SU453842A3 - - Google Patents

Description

(54) METHOD FOR OBTAINING OPTICALLY ACTIVE 1,4-BENZODIAZEPINES N-C. S-R, / V HN H where Ri-RS and A have the indicated values. By cleaving the protective group A from compounds IV, a free amino group is obtained, which then reacts with the carbonyl group, and compounds of general formula I are formed. According to the invention, the reaction of compounds II and III is carried out in an inert solvent and the removal of protective group A from compounds of general formula IV or acidic environment. Example 1. 2.32 g (10 mol) of 2-amino-5-chlorobenzophenoia and 1.89 g (10 mol) of BOC-L alkania are dissolved in 50 ml of CHgClg and 2.26 g (11 mmol) DCCD (dicyclocarbodiimide). After 30 minutes, the refrigerator was removed and the solution was stirred at room temperature overnight. The solution retains the yellow color of a partly unreacted amine. The released dicyclohexyl urea is sucked off and the filtrate is evaporated to a volume of approximately 3-4 ml. The concentrated solution is subjected to chromatography on a column (220 g of silica gel, chloroform - ethyl acetate 95: 5) and 69% of the crude product of the formula V X is obtained from fractions 16-28 (50 ml each) in half an hour to 35-40 ° C. Dried extracts (CaCl2, Na2S04) are evaporated and 90% of crude (+) -7-chloro-1,3-dihydro-3-methyl-5-phenyl-2H - 1,4-benzodiazepin-2oia (3 S) purified by recrystallization from ether. Melting points: 163-165 ° C NMR (vSSN1z), I5.8 171.5, 201. In + 332.5,. + 444, + 338 ° (С 1.56 in СНС1з). EXAMPLE 2 H O, HNGs) 0 / v HN H Compound VI of the above formula is prepared in the same way as Compound V, and 2.65 g (10 mmol) of BOC-L-phenylalanine is used. The crude product is isolated after removing the dicyclohexyl urea by evaporation of the solvent in vacuo and successive crystallization of the residue, starting with 50 ml of ethereal solution. 2.8 g (58.5%) of crude compound VI are obtained, m.p. 135-139 ° C. After recrystallization from dioxane-petroleum ether (twice), the melting point rises to 14 ° C. 1.5 g of compound VI is cyclized as described in Example 1. At the same time, 0.6 g of crude (+) -7-chloro-1,3-dihydro3-beisyl-5-phenyl-1,4-benzodiaziein-2-one (3S) is obtained. EXAMPLE 3 Analogously to Examples 1 and 2, when using 1.5 g of BOC-tyrosine, Compounds VII and VIII are obtained, the formulas of which are given below.

with t. pl. 148-153 ° C. After repeated recrystallization from cyclohexane, the product melts at 153-155 ° C. IR-hairs (in KBG) are clearly expressed at 3310, 1710 (shoulder), 1678, 1648, 1575, 1520, 1490, 1285, 1250, 1160, 955 cm-1.

Calculated,%; C, 62.61; H 5.75; N 6.95.

C2lH23N2O4Cl.

Found,%: C 62.48; H 5.11; N 6.72.

885 mg of Compound V is dissolved by transferring to 4 ml of glacial acetic acid. Under vigorous stirring, 5 ml of conicity with HCl is added to the solution and stirred for 10 minutes to remove the bubbles from the solution. The reaction mixture is added dropwise to 100 ml of a 10% aqueous solution of Ma2CO3 and heat I II

. ... SI,

C1

Subject invention

1. A method for producing optically active 1,4-benzodiazepines of the general formula

6

where RI and Rz have the indicated meanings, are reacted with a compound of the general formula

,

containing in position 3 asymmetric carbon atom,

where RI is hydrogen, halogen or nitrocorn, R2 is hydrogen or lower alkyl containing up to four carbon atoms,

Cs - normal or iso-lower alkyl,

containing up to three carbon atoms, substituted lower alkyl, benzyl, p-hydroxybenzyl or tryptophanil residue, characterized in that the compound of the general formula

..

Noos xB

WITH

Hn th

Claims (2)

I a where Rs has the indicated meanings, A is an H-HC1 group, a tre-butoxycarbonyl group or a phthalimide group, followed by cyclization of the intermediate compound of the general formula R o  I ii.  x n X n where RI-Rs and A have the indicated meanings, and isolating the target product by conventional techniques. 2. A method according to claim 1, characterized in that the reaction is carried out in an inert solvent.