CS224980B1 - The production of heterocyclic lactam-esters - Google Patents

Description

A process for the preparation of heterocyclic lactam esters

wherein R is C 1 -C 4 alkyl and n is 1 or 2.

The compounds of formula I are important intermediates in the production of biologically active substances.

The process according to the invention is characterized in that the diesters of symmetrical ketodicarboxylic acids of the general formula II,

ROOC-CIL · - (CH ₀ ) -CO-CH ₀ - (CH ₉ ) -COOR (II) and and in which R in are as hereinbefore defined, heat to boiling with the tryptamine of formula (III).

(III)

224,980 in a boiling organic solvent such as xylene, diglyme, diphenyl ether or chlorobenzene.

The following examples illustrate but do not limit the generality of the inventive process.

He did

A mixture of 0.80 g (5 mmol) of tryptamine (III) and 1.01 g (5 mmol) of dimethyl 4-oxo-1,7-heptanedioate (II, R = CH3, n = 1) in 15 ml of xylene is added. The mixture is heated to boiling for 65 hours and the solvent is distilled off under reduced pressure. The residue was dissolved in 50 ml of chloroform and washed successively with 15 ml of 5% hydrochloric acid, 15 ml of water and 10 ml of brine. After drying over sodium sulfate, the organic layer is evaporated in vacuo and the residue is chromatographed on 10 g of silica gel. The combined benzene-chloroform eluates (3 to 2: 1) were evaporated in a vacuum evaporator and the residue was crystallized from ethyl acetate. 0.74 g (47.6%) of the lactam ester of formula I (R = CH3, n = 1) is obtained, m.p. 179-181 ° C.

Example 2

A mixture of 2.30 g (10 mmol) of dimethyl 5-oxo-1,9-nonanedioate (II,

R = CH3, n = 2), 1.60 g (10 mmol) of tryptamine (III) and 35 ml of diglyme are heated to boiling for 12 h and then concentrated under reduced pressure. The residue is chromatographed on 25 g of silica gel. The combined benzene-chloroform (5 to 2: 1) eluates were evaporated on a rotary evaporator and crystallized from ethyl acetate. 1.54 g (45.1%) of the lactam ester of formula I (R = CH3, n-2) are obtained.

Example 3

A mixture of 1.61 g (7 mmol) of diethyl 4-α-1,7-heptanedioate (II),

R = CH ^CHg, η = 1) and 0.96 g (6 mmol) of tryptamine (III) are heated in 50 ml of chlorobenzene to boiling for 25 h. The reaction mixture is worked up as in Example 1. 0.77 g (39.5%) of the lactam ester of formula I (R = η-1), m.p. 196-199 ° C.

Following the procedure of Example 2, 20% -7% of the lactam ester of formula I (R = CH3CH3CH3Cl2, n = 1) was obtained from dibutyl 4-oxo-1,7-heptanedioate (II, R = CH3CH3CH3CH3Cl2, n = 1). = 1) in the form of transparent glass.

Example5

Following the procedure of Example 2, except that diphenyl ether was used instead of diglyme, 22-9% of the lactam ester of formula was obtained from dibutyl 5-oxo-1,9-nonanedioate (II, R = CH-CH 2 CH 2 CH 2, n = 2). I (R = CH ^CHgCHgCHg, n = 2) as a transparent glass.

Claims (1)

Object of the invention 224 980 A process for the preparation of heterocyclic lactam esters of the general formula wherein R is C1 -C4 alkyl and n is 1 or 2, characterized in that the esters of symmetrical ketodicarboxylic acids of the formula II are: ROOC-CH "- (CH GH.J -C 0 _o - (CH _a) -COOR (II) d d. Nddn in which R i n have from above said importance, tryptamine ITT formulas IJ H νη ^ heated to boiling in a boiling organic solvent such as xylene, diglyme, biphenyl ether or chlorobenzene. (III)