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 PDFInfo
- Publication number
- 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
- Authority
- US
- United States
- Prior art keywords
- dihydro
- producing
- benzodiazepines
- ones
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- 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.
Landscapes
- 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
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. |
Publications (1)
Publication Number | Publication Date |
---|---|
US3513159A true US3513159A (en) | 1970-05-19 |
Family
ID=8135555
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US663499A Expired - Lifetime US3513159A (en) | 1966-09-09 | 1967-08-28 | Method of producing 1,2-dihydro-1,4-benzodiazepines-2-ones |
Country Status (9)
Country | Link |
---|---|
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)
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 |
-
1966
- 1966-09-09 DK DK466266AA patent/DK124260B/en unknown
-
1967
- 1967-08-28 US US663499A patent/US3513159A/en not_active Expired - Lifetime
- 1967-08-30 FI FI672330A patent/FI47772C/en active
- 1967-09-01 DE DE19671645992 patent/DE1645992A1/en active Pending
- 1967-09-04 NL NL6712101A patent/NL6712101A/xx unknown
- 1967-09-04 CH CH1235667A patent/CH487907A/en not_active IP Right Cessation
- 1967-09-05 NO NO169616A patent/NO123180B/no unknown
- 1967-09-06 SE SE12298/67A patent/SE335988B/xx unknown
- 1967-09-07 ES ES344822A patent/ES344822A1/en not_active Expired
Patent Citations (1)
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 |
Also Published As
Publication number | Publication date |
---|---|
CH487907A (en) | 1970-03-31 |
FI47772C (en) | 1974-03-11 |
ES344822A1 (en) | 1968-11-01 |
SE335988B (en) | 1971-06-21 |
NO123180B (en) | 1971-10-11 |
DE1645992A1 (en) | 1970-07-16 |
FI47772B (en) | 1973-11-30 |
DK124260B (en) | 1972-10-02 |
NL6712101A (en) | 1968-03-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4585861A (en) | 1,2,4-triazine derivatives | |
US3513159A (en) | Method of producing 1,2-dihydro-1,4-benzodiazepines-2-ones | |
US3923710A (en) | Production of quinazolinone compounds | |
US3558603A (en) | Process for producing benzodiazepine derivatives | |
US3176017A (en) | Aroylalkyl derivatives of diazabicyclo-nonanes and-decanes | |
US3249610A (en) | Synthesis of 3-amino, 5-chloro, 6-substituted-pyrazinoates | |
US2624730A (en) | 6-haloaryl-3-pyridazones | |
US3910911A (en) | Production of quinazolinone compounds | |
Rees et al. | Ring contraction of 1, 2, 4-triazin-3-ones to imidazolin-2-ones and 1, 2, 3-triazoles | |
Rovnyak et al. | Preparation of thiopyrano-and pyrano [4, 3-c] pyrazoles. Structure elucidation of dehydro coproducts | |
US3321469A (en) | Compounds of phenylazepines and benzodiazepine esters of polycarboxylic acids | |
US3757006A (en) | Process for the production of 5-phenyl-1,4-benzodiazepines | |
Taylor et al. | Efficient synthesis of 5‐substituted‐4, 5‐dihydro‐1, 2, 4‐triazin‐6‐ones and 5‐substituted‐1, 2, 4‐triazin‐6‐ones | |
US3560482A (en) | Method for producing benzodiazepine derivatives | |
US3562272A (en) | Preparation of 4-aryl-2(1h)-quinazolinones | |
US3336296A (en) | Preparation of 5-substituted-2h-1, 4-benzodiazepin-2-one-4-oxides | |
US3632573A (en) | Method for producing benzodiazepine derivatives | |
US3674777A (en) | Process for preparing 1,3-dihydro-5-phenyl-2h-1,4-benzodiazepine-2-thiones | |
SHIOKAWA et al. | Studies on Benzimidazoles and Related Compounds. IV. Reactivity of 2-Azido-1-methylbenzimidazole | |
US3371084A (en) | Process for preparing halogen-substituted-1, 4-benzodiazepines | |
Buscemi et al. | Heterocyclic rearrangements. Synthesis of 1, 2, 4‐oxadiazolo [2, 3‐a] pyrimidinium systems and their ring opening into pyrimidine N‐oxides | |
US4579685A (en) | Process for preparing 1-substituted-1,4-benzodiazepine derivatives | |
US3766169A (en) | Process for the preparation of 3-aminomethylidene - 1,5 - benzodiazepine-2,4-(3h,5h)-diones | |
US3322753A (en) | Oxidation of certain 5-phenyl-1, 4-benzodiazepinones | |
US3504015A (en) | N-(2-aroylphenyl)glycine derivatives |