US3513159A - Method of producing 1,2-dihydro-1,4-benzodiazepines-2-ones - Google Patents

Method of producing 1,2-dihydro-1,4-benzodiazepines-2-ones Download PDF

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US3513159A
US3513159A US663499A US3513159DA US3513159A US 3513159 A US3513159 A US 3513159A US 663499 A US663499 A US 663499A US 3513159D A US3513159D A US 3513159DA US 3513159 A US3513159 A US 3513159A
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dihydro
producing
benzodiazepines
ones
phenyl
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US663499A
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Hjarne Paul Correll Dyrsting
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Xellia Pharmaceuticals ApS
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Dumex AS
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
    • C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
    • C07D243/24—Oxygen atoms

Definitions

  • the invention relates to a novel method of producing l-alky] 1,2 dihydro 3H 5 phenyl-1,4-benzodiazepin- 2-ones by oxidizing the corresponding 1,2,4,5-tetrahydro compounds with azodicarboxylic acid diethyl ester.
  • This invention relates to a method of producing l-alkyl- 1,Z-dihydro-3H-2-oxo-5-phenyl-1,4-benzodiazepines of the general formula R2 f 1 XQ /C]EI2 I R (I) wherein X represents hydrogen, halogen, a nitro group, a nitroso group, an alkyl group, a trifluoromethyl group or a hydroxy group, R represents a phenyl group, which may be substituted, and R represents a lower alkyl group, preferably a methyl group.
  • 1,4-benzodiazepines of the general formula ⁇ CH-NH R (II) wherein X and R are as hereinbefore described can be oxidized by means of common oxidizing agents, such as CrO to establish a double bond in the 4,5-position.
  • reaction proceeds smoothly, swiftly, and completely quantitatively, which is a great advantage, because the purification problems are avoided, which are characteristic for the oxidation methods using common oxidizing agents as mentioned hereinbefore.
  • the compounds resulting from the present method are of strongly sedative and tranquilizing effect.
  • the present method is illustrated by the following example.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Description

United States Patent 3,513,159 METHOD OF PRODUCING 1,2-DIHYDRO-1,4-
BENZODIAZEPINES-Z-ONES Hjarne Paul Correll Dyrsting, Virum, Denmark, assignor to A/ S Dumex (Dumex Ltd.), Copenhagen, Denmark, a Danish company No Drawing. Filed Aug. 28, 1967, Ser. No. 663,499 Claims priority, application Denmark, Sept. 9, 1966, 4,662/ 66 Int. Cl. C07d 41/08 U.S. Cl. 260-2393 2 Claims ABSTRACT OF THE DISCLOSURE The invention relates to a novel method of producing l-alky] 1,2 dihydro 3H 5 phenyl-1,4-benzodiazepin- 2-ones by oxidizing the corresponding 1,2,4,5-tetrahydro compounds with azodicarboxylic acid diethyl ester.
This invention relates to a method of producing l-alkyl- 1,Z-dihydro-3H-2-oxo-5-phenyl-1,4-benzodiazepines of the general formula R2 f 1 XQ /C]EI2 I R (I) wherein X represents hydrogen, halogen, a nitro group, a nitroso group, an alkyl group, a trifluoromethyl group or a hydroxy group, R represents a phenyl group, which may be substituted, and R represents a lower alkyl group, preferably a methyl group.
It is known that 1,4-benzodiazepines of the general formula \CH-NH R (II) wherein X and R are as hereinbefore described, can be oxidized by means of common oxidizing agents, such as CrO to establish a double bond in the 4,5-position.
If, however, the nitrogen atom in the l-position is substituted with an alkyl group, for example a methyl group, it has not hitherto been possible, by means of the usual oxidizing agents, to accomplish an oxidation to introduce the said double bond, since the oxidation in that case goes on to yield mainly the corresponding 2,3-dioxo compound (J. Org. Chem., 30 (1965), 1308).
According to the present invention it has now surprisingly been found that the compounds of Formula I above can be produced by reacting a compound of the general formula 3,513,159 Patented May 19, 1970 wherein X, R and R are as hereinbefore defined, with the diethyl ester of azodicarboxylic acid, according to the following scheme of reaction:
The reaction proceeds smoothly, swiftly, and completely quantitatively, which is a great advantage, because the purification problems are avoided, which are characteristic for the oxidation methods using common oxidizing agents as mentioned hereinbefore.
In a preferred embodiment of the present method 1- methyl 1,2,4,5 tetrahydro 5 phenyl 3H 7 chloro- 1,4-benzodiazepin-2-one is oxidized to 1-methyl-1,2-dihy dro-S-phenyl-3H-7-chloro-1,4-benzodiazepin 2 one by means of azodicarboxylic acid diethyl ester.
As is known, the compounds resulting from the present method, and especially the above identified compound, are of strongly sedative and tranquilizing effect.
The present method is illustrated by the following example.
EXAMPLE To 1.4 g. of l-methyl-l,2,4,5-tetrahydro-5-phenyl-3H-7- chloro-1,4-benzodiazepin-2-one dissolved in 20 ml. of dry benzene are added 0.87 g. of azodicarboxylic acid diethyl ester.
The mixture is refluxed for one hour and left overnight at room temperature. The precipitated crystals of hydrazodicarboxylic acid diethyl ester are sucked off, yielding 0.7 g. of MP. -133 C. The benzene solution is evaporated in vacuo to dryness. The residue is dissolved in 10 ml. of boiling isopropanol. By cooling the solution, 1.1 g. of l-methyl-l,Z-dihydro-S-phenyl-3H-7-chloro-1,4-benzodiazepin-Z-on of MP. 128130 C. are precipitated.
I claim:
1. Method of producing l-alkyl-1,2-dihydro-3H-5-phenyl-1,4-benzodiazepin-2-ones of the formula wherein X is a member of the group consisting of hydrogen, and halogen, R is a phenyl group, and R is a lower alkyl group, comprising the step of oxidizing a compound of the formula R2 1 Ic=0 X 011:
\(JHNH R (III) wherein X, R and R are as above defined, with azodicarboxylic diethyl ester.
2. The method of claim 1, in which the starting mate- 4 rial is l-rnethyl-1,2,4,5-tetrahydro-5-phenyl-3H-7-chlorol,4-benzodiazepin-2-one.
References Cited UNITED STATES PATENTS 3,371,085 2/1968 Reeder et a1 260--239.3
HENRY R. JILES, Primary Examiner R. T. BOND, Assistant Examiner US. Cl. X.R. 260-192, 482, 999
US663499A 1966-09-09 1967-08-28 Method of producing 1,2-dihydro-1,4-benzodiazepines-2-ones Expired - Lifetime US3513159A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DK466266AA DK124260B (en) 1966-09-09 1966-09-09 Process for the preparation of 1-alkyl-1,2-dihydro-3H-2-oxo-5-phenyl-1,4-benzodiazepine compounds.

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US (1) US3513159A (en)
CH (1) CH487907A (en)
DE (1) DE1645992A1 (en)
DK (1) DK124260B (en)
ES (1) ES344822A1 (en)
FI (1) FI47772C (en)
NL (1) NL6712101A (en)
NO (1) NO123180B (en)
SE (1) SE335988B (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3371085A (en) * 1959-12-10 1968-02-27 Hoffmann La Roche 5-aryl-3h-1,4-benzodiazepin-2(1h)-ones

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3371085A (en) * 1959-12-10 1968-02-27 Hoffmann La Roche 5-aryl-3h-1,4-benzodiazepin-2(1h)-ones

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Publication number Publication date
CH487907A (en) 1970-03-31
FI47772B (en) 1973-11-30
ES344822A1 (en) 1968-11-01
SE335988B (en) 1971-06-21
NO123180B (en) 1971-10-11
DK124260B (en) 1972-10-02
NL6712101A (en) 1968-03-11
FI47772C (en) 1974-03-11
DE1645992A1 (en) 1970-07-16

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