4',5'-Dimethoxy-2',3-diaminopropiophenone dihydrochloride

Abstract

4',5'-Dimethoxy-2',3-diaminopropiophenone dihydrochloride possesses pharmacological activity as a hypotensive agent.

Description

This invention relates to a compound of the formula: ##STR1##

When administered intravenously to animals this compound exhibits hypotensive activity. Intravenous administration of 50 mg/kg of this compound dissolved in physiologically acceptable menstrua to anesthetized dogs resulted in blood pressure lowering for about 5 hours.

In order that this invention be readily available to and understood by those skilled in the art, the following illustrative example is included: A. 3' ,4'-Dimethoxy-3-nitropropiophenone. Aluminum chloride (173 g, 1.30 moles) was added quickly to 700 ml vigorously stirred nitrobenzene. While the temperature was maintained between 10.degree. and 15.degree. there was added a solution of 91 g (0.59 mole) of .beta.-nitropropionyl chloride in 50 ml nitrobenzene followed by a solution of 73 g (0.53 mole) veratrole in 50 ml nitrobenzene. The mixture was stirred at room temperature for 6 hours and then poured cautiously into a mixture of 300 ml concentrated HC1and 2 kg iced water. The organic layer was separated and the aqueous material was extracted with 3 .times. 200-ml portions of chloroform. The combined organic layers were washed with 300 ml water, 300 ml 10% sodium carbonate, and 2 .times. 300-ml portions of water. After the solution was dried over magnesium sulfate, the solvents were removed in vacuo to give the oily product. Cystallization from ethyl acetate gave 45.5 g (36%) of A, m.p. 113-118.degree.. An analytical sample m.p. 126-128.degree., was obtained by recrystallization from ethanol.

Anal. Calcd for C.sub.11 H.sub.13 NO.sub.5 : C, 5.48; N, 5.86 Found: C, 55.11; H, 5.78; N, 5.59 B. 4' ,5'-Dimethoxy-2' ,3-dinitropropiophenone. To 300 ml concentrated nitric acid stirred and maintained at 5-10.degree. was added over 20 minutes in small portions 45.5 g (0.19 mole) of A. The resulting solution was stirred at 5.degree. for 10 minutes and then added slowly to 2.5 kg iced water. The suspension was stirred at room temperature for 20 minutes and filtered. The solid was washed with 3 .times. 200-ml portions of water, air dried, and dried at 60.degree. to give 48 g of crude B, m.p. 120-127.degree.. Recrystallization from 2 1. ethanol gave 34 g (63%) of B, m.p. 135-140.degree.. An analytical sample, m.p. 140-142.degree. , was obtained by recrystallization from alcohol.

Anal. Calcd for C.sub.11 H.sub.12 N.sub.2 O.sub.7 : C, 46.48 H, 4.26; N, 9.86 Found: C, 46.62; H, 4.39; N, 9.78 C. 4',5'-Dimethoxy-2' ,3-diaminopropiophenone dihydrochloride A 17.3 g (0.61 mole) portion of B, 500 ml methanol, 240 ml methanol saturated with HC1, and 22 g 5% Pd/C (50% moisture) was shaken on a Parr apparatus at room temperature until the theoretical quantity of hydrogen was consumed (5.5 hours). The catalyst was filtered and the resulting solution was concentrated to dryness at 35--45.degree. in vacuo. The residue was slurried with ethanol and the solid was filtered to give 13.5 g of the crude product, m.p. 204.degree.-209.degree..

The material was recrystallized from ethanol and the solid was washed with 70 ml ethanol to afford 5.3 g (29%) of the product, m.p. 208-214.degree..

An analytical sample, m.p. 202-207.degree., was recrystallized from ethanol containing HCl.

Anal. Calcd for C.sub.11 H.sub.18 N.sub.2 O.sub.3.sup.. 2HCl: C, 44.45; H, 6.10; N, 9.43 Found: C, 44,63; H, 6.35; N, 9.21

Claims

1. The compound of the formula: ##STR2##