US3324170A - Derivatives of 5h-dibenzo[a, d]cycloheptene - Google Patents
Derivatives of 5h-dibenzo[a, d]cycloheptene Download PDFInfo
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- US3324170A US3324170A US194659A US19465962A US3324170A US 3324170 A US3324170 A US 3324170A US 194659 A US194659 A US 194659A US 19465962 A US19465962 A US 19465962A US 3324170 A US3324170 A US 3324170A
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- This invention relates to a novel method for making derivatives of dibenzocycloheptenes and, more particularly, the invention relates to a method of making SH-dibenzo [a;d]-10,1l-dihydrocyclloheptenes and 5H-dibenzo[a,d] cyelo heptenes which are substituted at the 5-carbon atom with a secondary aminopropyl or secondary aminopropylidene radical.
- This invention also includes the synthesis of intermediates used for obtaining these products.
- the end compounds of the invention are useful in the treatment of mental health conditions as they are antidepressants and serve as mood elevators or psychic energizers.
- the compounds are preferably administered in the form of their acid addition salts and these salts are included in the scope of this invention.
- R which is removed during the process, suitably may be an alkyl or aryl radical, or a combination thereof, such as aralkyl, and X is a halogen.
- the method of the present invention begins with the known aminopropylidene or aminopropyl compounds which are described in several places in the literature, e.g., in British Patent Nos. 858,187 and 858,188, in the Journal of Organic Chemistry, volume 27, page 230, 1962 and elsewhere. These compounds are prepared from for example, the known 5H-dibenzo[a,d]cycloheptene 5- ones and 5H-dibenzo[a,d] 10,11 dihydrocycloheptene- 5-0nes which in turn may be prepared by using the process described by A. C.
- the first step of the method of the present invention involves the condensation of a tertiary aminopropylidene or tertiary aminopropyl derivative of a 5-H-dibenzo[a,d]-cycloheptene with a haloformate to produce a urethane intermediate.
- Suitable solvents are those which are inert, such as, aromatic hydrocarbons, such as benzene and toluene, aliphatichydrocarbons, such as, heptene, hexane and the like, halogen hydrocarbons, such as chloroform and carbon tetrachloride and ethers, such as tetrahydrofuran.
- the reaction may be carried out at room temperature although it is preferred to run it under reflux conditions and for a suitable period of time, preferably up to several hours.
- the urethane intermediate thus produced is then subjected to hydrolysis to convert the substituted carbamyl group of the urethane to a hydrogen atom.
- the hydrolysis is preferably carried out under basic or acidic conditions. In a typical run the urethane is refluxed under nitrogen in a solution of potassium hydroxide in n-butanol. At the completion of the hydrolysis the solvent is evaporated in vacuo and the residue is extracted with suitable solvents in order to isolate the hydrolyzed product.
- the product of the hydrolysis is the desired secondary aminopropylidene or secondary aminopropyl derivative of a SH-dibenzo[a,d]cycloheptene or 5H-dibenzo[a,d] 10,11- dihydrocycloheptene.
- the Grignard solution prepared is cooled to room temperature and stirred while a solution of 5.05 g. (0.0221 mole) of 5-chloro-5H-dibenzo[a,d]-cycloheptene, prepared using the process described by G. Berti in Gazz. Chem. Ital. 87, 293-309 (1957), in 25 ml. of dry tetrahydrofuran is added dropwise, external cooling being applied as required to maintain the temperature close to room temperature. When the addition is complete, the mixture is heated to refluxing for minutes. The bulk of the tetrahydrofuran then is distilled under reduced pressure, keeping the water-bath temperature at 50-60 C. The syrupy residue is dissolved in 75 ml.
- EXAMPLE VII 29.5 g. of 5-[3 (N-methyl N carbethoxyamino)- propyl]-5H-dibenzo[a,d]cycloheptene is refluxed for 24 hours under nitrogen in a solution of 36.3 g. of potassium hydroxide in 378 ml. of n-butanol. After cooling to room temperature, the solvent is evaporated in vacuo, the residue is stirred with 200 ml. of water, 300 ml. of n-hexane, the layers separated, the water layer extracted with 100 m1.
- EXAMPLE X Following the procedure described in detail in the above Examples IV through VI and using equivalent amounts of a mixture of acetic and hydrochloric acids in place of potassium hydroxide as the hydrolyzing medium there are produced the same monomethyl products as are produced in Examples IV through VI 6
- EXAMPLE XI Following the procedure described in detail in the examples above and using the following solvents: toluene, hexane, chloroform and tetrahydrofuran in place of benzene in Examples I through III, there are produced the same intermediate products.
- R is alkyl, aryl or aralkyl.
Description
United States Patent 3,324,170 DERIVATIVES OF 5H-DIBENZO[a,d]CYCLO- HEPTENE Janos Kollonitsch, Westiield, N.J., assignor to Merck & (30., Inc, Rahway, N.J., a corporation of New Jersey N0 Drawing. Filed May 14, 1962, Ser. No. 194,659 6 Claims. (Cl. 260-471) This invention relates to a novel method for making derivatives of dibenzocycloheptenes and, more particularly, the invention relates to a method of making SH-dibenzo [a;d]-10,1l-dihydrocyclloheptenes and 5H-dibenzo[a,d] cyelo heptenes which are substituted at the 5-carbon atom with a secondary aminopropyl or secondary aminopropylidene radical. This invention also includes the synthesis of intermediates used for obtaining these products.
The end compounds of the invention are useful in the treatment of mental health conditions as they are antidepressants and serve as mood elevators or psychic energizers. The compounds are preferably administered in the form of their acid addition salts and these salts are included in the scope of this invention.
The end compounds formed by the method of the invention may be represented by the following general formula:
CHzCHzNHCHa H CH1 .CHzCHzNHCHa H OH:
I CHzCH NHCHa 3,324,170 Patented June 6, 1967 The method of the present invention may be illustrated schematically by the following flow sheet in which the dotted lines indicate the compound may be saturated or unsaturated at the indicated positions and X and X are as previously defined.
Where R, which is removed during the process, suitably may be an alkyl or aryl radical, or a combination thereof, such as aralkyl, and X is a halogen.
The method of the present invention begins with the known aminopropylidene or aminopropyl compounds which are described in several places in the literature, e.g., in British Patent Nos. 858,187 and 858,188, in the Journal of Organic Chemistry, volume 27, page 230, 1962 and elsewhere. These compounds are prepared from for example, the known 5H-dibenzo[a,d]cycloheptene 5- ones and 5H-dibenzo[a,d] 10,11 dihydrocycloheptene- 5-0nes which in turn may be prepared by using the process described by A. C. Cope et al., entitled Cyclic Polyolefins, XV, 1-methylene-2,3,6,7 dibenzocycloheptatriene, appearing in the J.A.C.S. 73, 1673 to 1678 (1951). The starting compounds for the ketones, and particularly those having substituents on the benzene rings, may be made by following the teachings of T. W. Campbell et al., in an article entitled Synthesis of 2- acetamido-Z,3,6,7-dibenzotropilidene and 2 acetamido- 9,9-dimetl1ylfiuorene," appearing in Helv. Chem. Acta 36, 1489 to 1499 (1953).
As shown in the flow sheet above, the first step of the method of the present invention involves the condensation of a tertiary aminopropylidene or tertiary aminopropyl derivative of a 5-H-dibenzo[a,d]-cycloheptene with a haloformate to produce a urethane intermediate. In a typical run, 5-[3-N-dimethylaminopropylidene] 5H dibenzo [a,d] cycloheptene is reacted with methyl chloroformate to produce the urethane product, 5[3-(N-methyl-N-carbomethoXy-amino)propylidene] 5H dibenZo[a,d]-cycloheptene and methyl chloride.
While the reaction may be carried out in the absence of a solvent, it is preferable to employ a solvent. Suitable solvents are those which are inert, such as, aromatic hydrocarbons, such as benzene and toluene, aliphatichydrocarbons, such as, heptene, hexane and the like, halogen hydrocarbons, such as chloroform and carbon tetrachloride and ethers, such as tetrahydrofuran. The reaction may be carried out at room temperature although it is preferred to run it under reflux conditions and for a suitable period of time, preferably up to several hours.
At the conclusion of the reaction the solution is extracted with dilute acid and evaporated to dryness to yield the desired urethane. In a preferred reaction 5-[3- N-methylamino1propyl 5H dibenzo[a,d]cycloheptene is produced from the corresponding N-dimethyl starting compound.
The urethane intermediate thus produced is then subjected to hydrolysis to convert the substituted carbamyl group of the urethane to a hydrogen atom. The hydrolysis is preferably carried out under basic or acidic conditions. In a typical run the urethane is refluxed under nitrogen in a solution of potassium hydroxide in n-butanol. At the completion of the hydrolysis the solvent is evaporated in vacuo and the residue is extracted with suitable solvents in order to isolate the hydrolyzed product. The product of the hydrolysis is the desired secondary aminopropylidene or secondary aminopropyl derivative of a SH-dibenzo[a,d]cycloheptene or 5H-dibenzo[a,d] 10,11- dihydrocycloheptene.
The examples which follow will further illustrate the invention:
EXAMPLE I 5 [3-(N-methyl-N-ca rbethoxyamin)pr0pylidene] SH-dibenzo[a,d]cycloheptene A solution of -[3(N,N dimenthylamino) propylidene]-5H-dibenzo[a,d]cycloheptene (0.1 mol) is dissolved in 100 ml. of benzene and is added during one hour to a solution of 32.4 g. ethyl chloroformate (0.3 mol) in 100 ml. of benzene at room temperature. The solution is refluxed with stirring for two hours, cooled to room temperature, and extracted with 3X 100 ml. of 2.5 HCl. Washed with water (2x 50 ml.) dried over magnesium sulfate and evaporated to dryness. A thick oil is obtained representing pure urethane. The yield is 29.5 g. or 88% of the theoretical yield.
EXAMPLE II 5- (3-dimethylaminopropyl) -5H-dibenz0 [a,d]cycloheptene Magnesium turnings (1.08 g., 0.0442 g. atom) are placed in a 200 ml. 3-necked flask equipped with a stirrer, a dropping funnel and a reflux condenser carrying a drying tube. An atmosphere of dry nitrogen is maintained in the apparatus throughout the reaction. A crystal of iodine is added followed by ml. of dry tetrahydrofuran. A 3 ml. portion of 3-dimethylamino-propylmagnesium chloride solution from a previous experiment is added and the mixture heated to refluxing on the steam bath. A solution of 3-dimethylaminopropyl chloride (5.37 g., 0.0442 mole) in 35 ml. of dry tetrahydrofuran is added dropwise, refluxing being maintained by the application of heat when necessary. When the addition is complete, the mixture is refluxed for 2 hours when almost all of the magnesium is dissolved. Instead of using 3-dimethylaminopropylmagnesium chloride to initiate the reaction, ethyl bromide can be employed in a quantity of 0.05 mole per mole of magnesium.
The Grignard solution prepared is cooled to room temperature and stirred while a solution of 5.05 g. (0.0221 mole) of 5-chloro-5H-dibenzo[a,d]-cycloheptene, prepared using the process described by G. Berti in Gazz. Chem. Ital. 87, 293-309 (1957), in 25 ml. of dry tetrahydrofuran is added dropwise, external cooling being applied as required to maintain the temperature close to room temperature. When the addition is complete, the mixture is heated to refluxing for minutes. The bulk of the tetrahydrofuran then is distilled under reduced pressure, keeping the water-bath temperature at 50-60 C. The syrupy residue is dissolved in 75 ml. of benzene and water, 15 ml. is added dropwise with stirring. The benzene layer is decanted from the gelatinous precipitate which then is re-extracted with three 20 ml. portions of boiling benzene. The combined benzene extracts are washed with water and extracted with three 15 ml. portions of 3 N hydrochloride acid. The acid extract is made basic with sodium hydroxide and the yellow oily base that separates is extracted into hexane. After washing the combined extracts with water, the hexane is distilled and the product obtained as a yellow oil in a yield of 4.61 g.
EXAMPLE III 5 [3-(N-methyl-N-carbethoxyamino) pr0pyl1-5H-diben20 [a,d]cycloheptene 27.7 g. of 5-[3-(N-dimethylamino)propyl]-5H-dibenzo [a,d]cycloheptene (0.1 mol) dissolved in 100 ml. of henzene is added during one hour to a solution of 32.4 g. ethyl chloroformate (0.3 mol) in 100 ml. of benzene at room temperature. The solution is refluxed with stirring for 20 hours, cooled to room temperature, and extracted with 3X 100 ml. of 2.5 N HCl. Washed with water (2X 50 ml.) dried over magnesium sulfate and evaporated to dryness. A thick oil is obtained representing pure urethane. The yield is 29.5 g. or 88% of the theoretical yield.
EXAMPLE IV 5 [3-(N-methyl-N-carbomethoxyamino)propyl] -5H-dibenz0[a,d] OJI-dihydrocycloheptene 52.4 g. of 5[3-(N-dimethylamino)propyl1-5H-dibenzo [a,d]-l0,1l-dihydrocycloheptene (0.188 mol) is dissolved in 216 ml. of benzene and a solution of 65 g. of methyl chloroformate in 580 ml. of benzene is added during about 15 minutes which the mixture is stirred at room temperature. The solution is refluxed with stirring for two hours, cooled to room temperature, filtered, the filtrate extracted with 2.5 N HCl (3X 200 ml.), washed with water, dried over MgSO and evaporated in vacuo. A thick, colorless oil is obtained representing 56 g. urethane.
Following the procedure described in detail in Example I and using equivalent quantities of 5-[3-(N-dimethylamino)propylidene] 5H dibenzo[a,d]-10,1l-dihydrocycloheptene there is produced the corresponding 5-[3-(N- EXAMPLE V 5-[3-(N-methylamino)propylidene] 5H-dibenz0 [a,d]-cycloheptene 29.5 g. of 5-[3-(N-methyl-N-carbethoxyamino)-propylidene-5H-dibe'nzo[a,d]-cycloheptene is refluxed for 9 hours under nitrogen in a solution of 24.2 g. of potassium hydroxide in 255 ml. of n-butanol. After cooling to room temperature, the solvent is evaporated in vacuo, the residue is stirred with 200 ml. of water, 300 ml. of n-hexane, the layers separated, the water layer extracted again with 100 ml. of n-hexane, the combined layers washed with water (2X 100 ml.) and then with 0.5 N sulfuric acid (100x X ml.). The acid solution is then alkaliz/ed and extracted with ether (2X ml. and 1X 100 ml.), dried over MgSO and the solution evaporated to dryness. 19.7 g. of a slightly yellow clear thick oil is produced representing substantially pure monomethyl base product, M.P. 5455 (85% of theoretical yield).
EXAMPLE VI 5 [3-(N-methylamino)propylidene] -5H-dibenzo[a,d]- 10,11-dihydr0cycl0heptene 28.2 g. of 5[3-(N-methyl-N-carbethoxyamino)propylidene]5H-dibenzo[a,d] 10,11 dihydrocycloheptene is refluxed in a solution of 23.9 g. potassium hydroxide in 250 ml. of n-butanol for 6 hours in a nitrogen atmosphere under stirring. The solvent is removed in vacuo and to the residue there is added a mixture of 260 ml. of Water and 310 ml. of 2 N sulfuric acid and the mixture is heated to form a solution. The solution is then cooled to room temperature and extracted with 250 ml. n-hexane. Three layers are formed, the two layers are collected together and the upper hexane layer is extracted with 100 ml. of N sulfuric acid. The combined acid layers are alkalized by the addition of 50 ml. of 11.7 N sodium hydroxide solution, then extracted with ether, 3 170 ml., backwashed with water, dried over MgSO and evaporated to dryness. 21.5 g. of the desired monomethyl product is obtained (97% yield).
EXAMPLE VII 29.5 g. of 5-[3 (N-methyl N carbethoxyamino)- propyl]-5H-dibenzo[a,d]cycloheptene is refluxed for 24 hours under nitrogen in a solution of 36.3 g. of potassium hydroxide in 378 ml. of n-butanol. After cooling to room temperature, the solvent is evaporated in vacuo, the residue is stirred with 200 ml. of water, 300 ml. of n-hexane, the layers separated, the water layer extracted with 100 m1. of n-hexane and the combined hexane layers washed with water (2X 100 m1.) and then with 0.5 N sulfuric acid (100x 80X 80 ml.). The acid solution is then alk-alized and extracted with ether (2X 150 ml. and 1X 100 ml.) dried over MgSO and the solution evaporated to dryness. The product is a substantially pure monomethyl base product, which is then further purified by transformation to the oxalate (M.P. 181) liberation to the free base and conversion to the hydrochloride (M.P. 169-170).
Following the procedure described in detail above and using equivalent quantities of 5-[3-(N-methyl-N-carbomethoxyamino)propy1] 5H dibenzo-[a,d]-l0,ll-dihydrocycloheptene there is produced the corresponding 5- [3-(N-methylamino)-propyl] 5H dibenZo-[a,d]-10,11- dihydrocycloheptene.
EXAMPLE VIII Following the procedure described in detail in the above examples, and using equivalent quantities X and X as enumerated above, there is produced the corresporrding monomethyl product substituted With X and X substituents.
EXAMPLE IX Following the procedure described in detail above and using equivalent quantities of ethyl bromofonmate, phenyl chloroformate and benzyl bromoformate in place of methyl chloroformate and ethylchloroformate respectively. In Examples I through III there are formed the same monomethyl products as are produced in Examples 1V, V, and VI.
EXAMPLE X Following the procedure described in detail in the above Examples IV through VI and using equivalent amounts of a mixture of acetic and hydrochloric acids in place of potassium hydroxide as the hydrolyzing medium there are produced the same monomethyl products as are produced in Examples IV through VI 6 EXAMPLE XI Following the procedure described in detail in the examples above and using the following solvents: toluene, hexane, chloroform and tetrahydrofuran in place of benzene in Examples I through III, there are produced the same intermediate products.
What is claimed is:
1. A compound selected from a member of the group of compounds having the following formulae:
wherein R is alkyl, aryl or aralkyl.
2. A 5-[3 (N-methyl N hydrooarbonoxycarbonylamino) propyl]-SH-dibenzo [a,d] cycloheptene wherein the hydrocarbon moiety is alkyl, aryl or aralkyl.
3. A 5-[3 (N-methyl N hydrooarbonoxycarbonylamino) propyl] 10,11 dihydro-SH dibenzo[a,d]cycloheptene wherein the hydrocarbon moiety is alkyl, aryl or aralkyl.
4. A 5-[3 (N-methyl-N-loweralkoxycarbonylamino)- propyl] -5H-dibenzo [a,d] cycloheptene.
5. A 5-[3 (N-methyl-N-loweralkoxycarbonylamino)- propyl] 10,1 l-dihydro-SH-dibenzo a,d] cycloheptene.
6. A 5 3-(N-methyl-N-carbethoxyamino) -propyl] -5H- dibenzo a,d] cycloheptene.
References Cited UNITED STATES PATENTS 8/1953 Chenicek 260-482 OTHER REFERENCES LORRAINE A. WEINBERGER, Primary Examiner.
H. G. MOORE, Examiner.
L. ARNOLD THAXTON, M. S. JAROSZ,
Assistant Examiners,
UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No 3 ,324 ,170 June 6 1967 Janos Kollonitsch It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.
Column 3, line 33, for "dimenthylamino" read dimethylarnlno 11ne 38, after "2.5" insert N same column 3, 11ne 69, for "Chem." read Chim.
Signed and sealed this 20th day of August 1968.
(SEAL) Attest:
EDWARD J. BRENNER Commissioner of Patents Edward M. Fletcher, Jr.
Attesting Officer v
Claims (1)
1. A COMPOUND SELECTED FROM A MEMBER OF THE GROUP OF COMPOUNDS HAVING THE FOLLOWING FORMULAE:
Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US194659A US3324170A (en) | 1962-05-14 | 1962-05-14 | Derivatives of 5h-dibenzo[a, d]cycloheptene |
| NO148572A NO121948B (en) | 1962-05-14 | 1963-05-06 | |
| DEM56710A DE1287573B (en) | 1962-05-14 | 1963-05-06 | Process for the preparation of antidepressant 5- (3-methylaminopropyl) -5H-dibenzo [a, d] -cyclohepten |
| GB18414/63A GB1034931A (en) | 1962-05-14 | 1963-05-09 | Dibenzo [a,d]-cycloheptene derivatives |
| BR149044/63A BR6349044D0 (en) | 1962-05-14 | 1963-05-10 | PROCESS TO MAKE DIBENZO-CYCLE-HEPTENE DERIVATIVES |
| SE5277/63A SE318867B (en) | 1962-05-14 | 1963-05-13 | |
| FI0990/63A FI41020B (en) | 1962-05-14 | 1963-05-13 | |
| ES288362A ES288362A1 (en) | 1962-05-14 | 1963-05-13 | Method for obtaining derivatives of dibenzocicloheptenes (Machine-translation by Google Translate, not legally binding) |
| DK227363AA DK122073B (en) | 1962-05-14 | 1963-05-14 | Analogous process for the preparation of 5- [3- (N-methylamino) propyl] -5H-dibenzo- [a, d] -cycloheptenes or acid addition salts thereof. |
| CH603263A CH446310A (en) | 1962-05-14 | 1963-05-14 | Process for the preparation of dibenzo-cycloheptene derivatives |
| DK136064AA DK119608B (en) | 1962-05-14 | 1964-03-17 | Process for the preparation of dibenzocycloheptene derivatives. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US194659A US3324170A (en) | 1962-05-14 | 1962-05-14 | Derivatives of 5h-dibenzo[a, d]cycloheptene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3324170A true US3324170A (en) | 1967-06-06 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US194659A Expired - Lifetime US3324170A (en) | 1962-05-14 | 1962-05-14 | Derivatives of 5h-dibenzo[a, d]cycloheptene |
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| Country | Link |
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| US (1) | US3324170A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3379750A (en) * | 1962-05-14 | 1968-04-23 | Merck & Co Inc | 10, 11-dihydro-or-5-[3-(n-methyl-n-thiourethane amino)-propylidene-or-propyl-]5h-dibenzo cycloheptenes |
| US3435073A (en) * | 1966-04-19 | 1969-03-25 | Colgate Palmolive Co | 5-(n-benzyl-n-lower alkylaminoalkylene)-5h-dibenzo(a,d)cycloheptenes |
| US3513201A (en) * | 1966-10-25 | 1970-05-19 | Merck & Co Inc | Process for preparing 5-(3-alkylaminopropyl)-5h-dibenzo(a,d)cycloheptenes |
| US3905981A (en) * | 1973-10-12 | 1975-09-16 | Research Corp | N-dealkylation of tertiary amines |
| US4020096A (en) * | 1974-02-01 | 1977-04-26 | Merck & Co., Inc. | 10,11,Dihydro-N-alkoxycarbonyl-10,10,11,11-tetrafluoro-5H-dibenzo[a,d]cycloheptene-5-methylamines |
| US4307245A (en) * | 1978-12-29 | 1981-12-22 | Syva Company | Amitriptyline conjugates to antigenic proteins and enzymes |
| US4874793A (en) * | 1988-07-29 | 1989-10-17 | Darrell Franks | Use of protriptyline for the treatment of mental health problems in children |
| US5238959A (en) * | 1988-04-08 | 1993-08-24 | Eli Lilly And Company | 3-phenyloxy-3-phenyl propanamines |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2649473A (en) * | 1950-12-28 | 1953-08-18 | Universal Oil Prod Co | Substituted carbamic acid esters as surface active agents |
-
1962
- 1962-05-14 US US194659A patent/US3324170A/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2649473A (en) * | 1950-12-28 | 1953-08-18 | Universal Oil Prod Co | Substituted carbamic acid esters as surface active agents |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3379750A (en) * | 1962-05-14 | 1968-04-23 | Merck & Co Inc | 10, 11-dihydro-or-5-[3-(n-methyl-n-thiourethane amino)-propylidene-or-propyl-]5h-dibenzo cycloheptenes |
| US3435073A (en) * | 1966-04-19 | 1969-03-25 | Colgate Palmolive Co | 5-(n-benzyl-n-lower alkylaminoalkylene)-5h-dibenzo(a,d)cycloheptenes |
| US3513201A (en) * | 1966-10-25 | 1970-05-19 | Merck & Co Inc | Process for preparing 5-(3-alkylaminopropyl)-5h-dibenzo(a,d)cycloheptenes |
| US3905981A (en) * | 1973-10-12 | 1975-09-16 | Research Corp | N-dealkylation of tertiary amines |
| US4020096A (en) * | 1974-02-01 | 1977-04-26 | Merck & Co., Inc. | 10,11,Dihydro-N-alkoxycarbonyl-10,10,11,11-tetrafluoro-5H-dibenzo[a,d]cycloheptene-5-methylamines |
| US4307245A (en) * | 1978-12-29 | 1981-12-22 | Syva Company | Amitriptyline conjugates to antigenic proteins and enzymes |
| US5238959A (en) * | 1988-04-08 | 1993-08-24 | Eli Lilly And Company | 3-phenyloxy-3-phenyl propanamines |
| US4874793A (en) * | 1988-07-29 | 1989-10-17 | Darrell Franks | Use of protriptyline for the treatment of mental health problems in children |
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