US2802003A - Derivatives of 3-azabicycloheptane - Google Patents
Derivatives of 3-azabicycloheptane Download PDFInfo
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- US2802003A US2802003A US539652A US53965255A US2802003A US 2802003 A US2802003 A US 2802003A US 539652 A US539652 A US 539652A US 53965255 A US53965255 A US 53965255A US 2802003 A US2802003 A US 2802003A
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- azabicycloheptane
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- KZBSQARHJUFGCC-UHFFFAOYSA-N 3-cycloheptylazepane Chemical class C1CCCCCC1C1CNCCCC1 KZBSQARHJUFGCC-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 17
- 150000003839 salts Chemical group 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 239000002585 base Substances 0.000 description 18
- 238000000034 method Methods 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- -1 dimethylaminoethyl imide Chemical class 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 9
- UUAVYXKRUSVCDJ-UHFFFAOYSA-N 1-cycloheptylazepane Chemical compound C1CCCCCC1N1CCCCCC1 UUAVYXKRUSVCDJ-UHFFFAOYSA-N 0.000 description 8
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 150000003949 imides Chemical class 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- HTXWKZDRDRFVHN-UHFFFAOYSA-N 2-methyloxiran-2-ol Chemical compound CC1(O)CO1 HTXWKZDRDRFVHN-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- YIXVXFVKVAPMDM-UHFFFAOYSA-N trimethyl-[2-(trimethylazaniumyl)ethyl]azanium Chemical compound C[N+](C)(C)CC[N+](C)(C)C YIXVXFVKVAPMDM-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- QTULVYHYEGMYLW-UHFFFAOYSA-L trimethyl-[2-(trimethylazaniumyl)ethyl]azanium;diiodide Chemical compound [I-].[I-].C[N+](C)(C)CC[N+](C)(C)C QTULVYHYEGMYLW-UHFFFAOYSA-L 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NMNZZIMBGSGRPN-ZXZARUISSA-N (1s,5r)-3-oxabicyclo[3.2.0]heptane-2,4-dione Chemical compound O=C1OC(=O)[C@@H]2CC[C@H]12 NMNZZIMBGSGRPN-ZXZARUISSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
Definitions
- This invention relates to organic chemo-therapeutic agents and methods of their preparation, and more particularly relates to compounds of value in the treatment of cardio-vascular and other diseases. More specifically the invention relates to azabicycloheptane (3:2:0) bases, and the simple and monoand bis-quaternary salts thereof.
- the novel compounds discovered are obtained by forming the N-dialkylaminoalkyl imides from the anhydride of cis-l,2-cyclobutane dicarboxylic acid, the reduction of these imides by suitable means to obtain N- dialkylaminoalkyl-3-azabicycloheptane bases which may be converted by appropriate means into the simple, monoand bis-quaternary salts.
- Formula 1 shows the general structural formula of compounds obtained by the methods hereafter more par.- ticularly described. This formula depicts the free bases, and for convenience in representation the azabicycloheptane nucleus (enclosed in parenthesis, Formula 1) will be designated by the letter A hereafter.
- Formula 2 (0Hz) H 1 i wnsrif X ⁇ R X- X ⁇ R Formula 3(a) Formula 3(1))
- A represents the azabicycloheptane nucleus and n a number from I to 6.
- R represents two alkyl groups with from 1 to 6 carbon atoms.
- X- represents an anion namely, chloride, iodide, bromide, acetate or sulfate.
- the site of both simple and quaternary salt formation on the nucleus A is always the ring nitrogen at position 3.
- R may be the same as or different from R in any of the formulae given.
- the free bases, Formula 1, and their simple salts, Formula 2 possess varying degrees of antihistaminic and brochiodilatory activity.
- the dimeth iodide of Example I had a very favorable therapeutic ratio, at a total dosage level of 25 mg. I. M. there was a marked lowering of blood pressure and at the same time the toxicity has been determined to be 1250 mg./kg.
- the dihydrochlride.-'Ihe base was dissolved in anhydrous isopropanol and an excess of an alcoholic solution of HCl gas was added. On cooling and adding anhydrous ethyl ether, the dihydrochloride separated as crystalline white material with a melting point over 305 C.
- Ionic chloride Calculated-29.40%; found29.30%.
- the dimethiodide When the base was mixed with an excess of methyl iodide in anhydrous methanol and allowed to stand, the crystalline material crystallizing or precipitated out on adding anhydrous ether was generally a mixture of the monoand di-methiodides. In order to obtain the dimethiodide free of monomethiodide, it was necessary to reflux the base with an excess of methyl iodide in anhydrous methanol for 2-4 hours. The material that crystallized on cooling or on the addition of ether to the cooled reaction mixture melted at 215-219" C. On recrystallization from ethanol it melted at 219-221" C.
- the monomethiodide (This was obtained free from the dimethiodide by mixing molar equivalents of the free base and methyl iodide in methanol and letting the mixture stand a day at room temperature and adding ether to the cooled mixture. It had a melting point of 203-205 C. On recrystallization from isopropanol it crystallized in rectangular plates of melting point 204-206.
- the dimethiodide can be obtained directly by reacting the base with an excess of methyl iodide in acetone and allowing the mixture to stand 1 day. On refrigeration the dimethiodide separated in crystalline form, M. P. 230-233 C. decomposition. Recrystallization from absolute ethanol sharpened the M. P. to 23023l C. decomposition. Decomposition may set in lower than the melting point if the material is heated very slowly.
- Ionic chloride Calculated-27.78%; found-27.53%.
- the dimethi0dide The dimethiodide formed readily with excess methyl iodide and the base in acetone at room temperature on standing 1 day. M. P. 235-238 C. Recrystallization from isopropanol-ether gave M. P. 242-243" C.
- Ionic chloride Calculated-23.85%; found-24.00%.
- the dimethi0dide (This was formed analogous to Example III, M. P. 223230 C. decomposition. Recrystallization from ethanol, M. P. 230-2315 C., decomposition.
- a dimethonium 1.
- n is a number from 1 to 6
- R is selected from the group consisting of two alkyl groups each alkyl group having I to 6 carbon atoms and radicals which form, together with the nitrogen atom to which they are attached, heterocyclic groups consisting of morpholino, piperidino and pyrrolidino and (2) acid addition salts and mono and di-quaternary salts of 1).
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
United States Patent DERIVATIVES OF S-AZABICYCLOHEPTANE Charles H. Grogan, Falls Church, Va., and Leonard M. Rice, Baltimore, Md., assignors to The Geschickter Fund for Medical Research, Inc., Washington, D. C., a corporation of New York No Drawing. Application October 10, 1955, Serial No. 539,652
11 Claims. (Cl. 260-2475) This invention relates to organic chemo-therapeutic agents and methods of their preparation, and more particularly relates to compounds of value in the treatment of cardio-vascular and other diseases. More specifically the invention relates to azabicycloheptane (3:2:0) bases, and the simple and monoand bis-quaternary salts thereof.
It is a basic objective of the present invention to provide novel organic compounds and methods for their preparation.
It is another object of the invention to provide novel, physiologically active compounds having chemotherapeutic or medicinal properties, particularly hypotensive ac tivity.
It is a further object of the invention to provide novel compounds comprising N-dialkylaminoalkyl-3-azabicycloheptane (3:2:0) bases and the simple, monoand hisquaternary salts thereof, and methods of synthesizing these compounds.
These and other objects and the manner in which they are accomplished will become apparent to those conversant with the art from the following description of the general class of compounds and certain specific examples of particular members as well as general and specific methods for their synthesis.
Generally stated, the novel compounds discovered are obtained by forming the N-dialkylaminoalkyl imides from the anhydride of cis-l,2-cyclobutane dicarboxylic acid, the reduction of these imides by suitable means to obtain N- dialkylaminoalkyl-3-azabicycloheptane bases which may be converted by appropriate means into the simple, monoand bis-quaternary salts.
nocc J H H H Formula 1 Formula 1 shows the general structural formula of compounds obtained by the methods hereafter more par.- ticularly described. This formula depicts the free bases, and for convenience in representation the azabicycloheptane nucleus (enclosed in parenthesis, Formula 1) will be designated by the letter A hereafter.
The simple salts of the bases illustrated by Formula I are shown by Formula 2 while the monoand bis-quater- Patented Aug. 6, 1957 ice nary salts of these bases are shown by Formulae 3(a) and 3(b) respectively.
Formula 2 R! (0Hz) H 1 i wnsrif X \R X- X \R Formula 3(a) Formula 3(1)) In these formulae A represents the azabicycloheptane nucleus and n a number from I to 6. R represents two alkyl groups with from 1 to 6 carbon atoms. R represents an alkyl group with from 1 to 6 carbon atoms, an alkylene group containing 3 carbon atoms, or the structure (N=R)' may represent a heterocyclic ring namely, morpholine, piperidine, pyrrolidine, piperazine or N- methyl piperazine. X- represents an anion namely, chloride, iodide, bromide, acetate or sulfate. The site of both simple and quaternary salt formation on the nucleus A is always the ring nitrogen at position 3. In the quaternary salts R may be the same as or different from R in any of the formulae given.
The free bases, Formula 1, and their simple salts, Formula 2, possess varying degrees of antihistaminic and brochiodilatory activity. The quaternary salts of these bases, Formula 3(a), 3(b), and in particular the hisquaternary salts, Formula 3(b), possess a marked hypotensive activity in mammals. For example the dimeth iodide of Example I had a very favorable therapeutic ratio, at a total dosage level of 25 mg. I. M. there was a marked lowering of blood pressure and at the same time the toxicity has been determined to be 1250 mg./kg.
The following examples of specific compounds and methods will illustrate the manner in which the general synthesizing procedure may be applied to obtain particular members of the class of compounds discovered. It
4 will be understood, however, that the following examples are merely illustrative and are not, nor are they intended to be, exhaustive of all the compounds embraced by the present invention.
EXAMPLE I N-dimethylaminoethyl-3-azabicycl0heptane (3:2:0)
simple salts and quaternary salts The free base.24.5 grams of the dimethylaminoethyl imide of 1,2-cis-cyclobutane dicarboxylic anhydride, dissolved in 200 ml. of anhydrous ether was added to a rapidly stirred solution of 15 g. of lithium aluminum hydride (LiAlH4) in 600 ml. of anhydrous ethyl ether. Addition was made so as to just maintain reflux. The mixture was stirred for 2 hours after all the imide solution had been added, allowed to stand overnight and then decomposed by the dropwise addition of water so that reflux was just maintained. When the evolution of hydrogen had ceased, a slight excess of water was added, the mixture stirred 1-3 hours, inorganic material filtered off and the residue washed several times with ether. The ethereal filtrate was dried over anhydrous sodium sulfate, the ether stripped off and the residue vacuum distilled tg yield 17.7 grams of colorless liquid with an amine-like odor, B. P. 38-44" C./0.3 mm.: n =1.4766.
The dihydrochlride.-'Ihe base was dissolved in anhydrous isopropanol and an excess of an alcoholic solution of HCl gas was added. On cooling and adding anhydrous ethyl ether, the dihydrochloride separated as crystalline white material with a melting point over 305 C.
Ionic chloride: Calculated-29.40%; found29.30%.
The dimethiodide.-When the base was mixed with an excess of methyl iodide in anhydrous methanol and allowed to stand, the crystalline material crystallizing or precipitated out on adding anhydrous ether was generally a mixture of the monoand di-methiodides. In order to obtain the dimethiodide free of monomethiodide, it was necessary to reflux the base with an excess of methyl iodide in anhydrous methanol for 2-4 hours. The material that crystallized on cooling or on the addition of ether to the cooled reaction mixture melted at 215-219" C. On recrystallization from ethanol it melted at 219-221" C.
Ionic iodide: Calculated-56. 14%; found-55.94%
The monomethiodide.-This was obtained free from the dimethiodide by mixing molar equivalents of the free base and methyl iodide in methanol and letting the mixture stand a day at room temperature and adding ether to the cooled mixture. It had a melting point of 203-205 C. On recrystallization from isopropanol it crystallized in rectangular plates of melting point 204-206.
Ionic iodide: Calculated-40.91% found-41. 16%
EXAMPLE II N-diethylaminoethyl-3-azabicycl0heptane (3:2:0) simple and quaternary salts Carbon Hydrogen Nitrogen Calculated. Percent 73. 41 12. 32 14. 27 Found, Percent 73. 23 i2. 19 14. 46
The dihydr0chI0ride.-Addition of an excess of a saturated solution of HCl in ethanol to the base dissolved in isopropanol, cooling and addition of. ether produced the white crystalline dihydrochloride, M. P. 2142l6 C. Recrystallization from isopropanol gave M. P. 215-216" C.
Ionic chloride: Calculated-26.34%; found-26.10%.
The dimethiodide.The dimethiodide can be obtained directly by reacting the base with an excess of methyl iodide in acetone and allowing the mixture to stand 1 day. On refrigeration the dimethiodide separated in crystalline form, M. P. 230-233 C. decomposition. Recrystallization from absolute ethanol sharpened the M. P. to 23023l C. decomposition. Decomposition may set in lower than the melting point if the material is heated very slowly.
Ionic iodide: Calculated-52.86%; found-52.79%.
EXAMPLE III N-dimethyIamin0pr0pyl-3-azabicycloheptane (3:2:0) simple and quaternary salts The free base.Reduction of 28 grams of the appropriate imide with 15 g. of lithium aluminum hydride 4 (LiAlI-Is) as detailed under Example I yielded 22 grams of the title base, B. P. 53-55 C./0.3 mm., n =1.4702.
Carbon Hydrogen Nitrogen Calculated, Percent 72. 47 12. 16 15. 37 Found, Percent 72. 63 12. 27 15. 6B
The dihya'rochI0ride.-Addition of excess alcoholic- HCl to the base in isopropanol and precipitation with ether yielded the salt with M. P. 265-268 C. Recrystallization from isopropanol-ether gave M. P. 265C.
Ionic chloride: Calculated-27.78%; found-27.53%.
The dimethi0dide.The dimethiodide formed readily with excess methyl iodide and the base in acetone at room temperature on standing 1 day. M. P. 235-238 C. Recrystallization from isopropanol-ether gave M. P. 242-243" C.
Ionic iodide: Calculated-54.4S%; found-54.48%.
EXAMPLE IV N-diethylaminopropyl-3-azabicycl0heptane (3:2:0) salts and quaternary salts The free base.-Reducti0n of the corresponding imide The dihydrochloride.-This was formed analogous to Example Ill, M. P. 19l-192 C., with no change on recrystallization from isopropanol-ether.
Ionic chloride: Calculated25.03%; found-25.20%.
The dimcthi0dide.-This was also formed analogous to Example III, M. P. -187 C. Recrystallization from isopropanol-ether, M. P. l89-l90 C.
Ionic iodide: Calculated-51.36%; found-51.25%.
EXAMPLE V N-morpholinoethyl-3azabicycloheptane (3:2:0) salts and quaternary salts The free base.-l5 grams of the imide reduced with 6 grams of lithium aluminum hydride (LiAlH4) as detailed under Example I, yielded 11 grams of the base, B. P.
The dihydr0chl0ride.This was formed analogous to Example III, M. P. 271-273 C., with no change on recrystalliztaion.
Ionic chloride: Calculated-23.85%; found-24.00%.
The dimethi0dide.-This was formed analogous to Example III, M. P. 223230 C. decomposition. Recrystallization from ethanol, M. P. 230-2315 C., decomposition.
Ionic iodide: Calculated-49.94%; found-50.06%.
From the foregoing description of a novel class of compounds, and the detailed preparation and characterization of exemplary members of the class, it will be understood that, on the basis of the discovery and knowledge disclosed herein, other specific compounds can be made and variations in the methods of synthesis resorted to. The appended table contains additional examples of bases prepared by the procedures detailed herein. Therefore, the specific compounds and methods disclosed herein are to be considered in all respects as illustrative and not restrictive, the scope of the discovery being indicated by the appended claims rather than the foregoing descriptive detailed examples, and all specific compounds and variations and methods which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
N-DIETHYLAMINOETHYL-3-AZABIOYOLOEEPTANE (322:0)
Analysis, Percent 13. P., N substituent 0. mm Carbon Hydrogen Nitrogen Calcd Found Calc'd Found Cale'd Found diethylamlnobutyL 63-68 0. 3 74. 94 d1ethy1aminoamyl. 77-83 0. 3 75. 56 diethylaminohexyl- Q4-99 0. 3 76. 12 dibutylaminoethyl- 94-99 0. 1 76. 12 dlhex lamlnoethyl--. 118122 0.08 77.85 morp olinoethyl 72-78 0,3 68.53 plparldinoethyL- 80-84 0. 2 74. 04
We claim: 5. As a novel composition of matter, a dimethonium 1. As a novel composition of matter, a compound selected from the group consisting of (1) compounds having the formula H1CC--C N(OH|)--N==R H:CCC/
H H: where, in said formula, n is a number from 1 to 6, R is selected from the group consisting of two alkyl groups each alkyl group having I to 6 carbon atoms and radicals which form, together with the nitrogen atom to which they are attached, heterocyclic groups consisting of morpholino, piperidino and pyrrolidino and (2) acid addition salts and mono and di-quaternary salts of 1).
2. As a novel composition of matter, a dimethonium salt of N dimethylaminoethyl 3 azabicycloheptane (3:210).
3. As a novel composition of matter, a dimethonium salt of N diethylaminopropyl 3 azabicycloheptane (3:2:0).
6. As a novel composition of matter, a dimethonium salt of N morpholinopropyl 3 azabicycloheptane (3:2:0).
7. As a novel composition of matter, N-dimethylaminoethyl-3 -azabicycloheptane (3 2: 0)
8. As a novel composition of matter, the dimethonium chloride of N-dimethylaminoethyl 3 azabicycloheptane (3:2:0).
9. As a novel composition of matter, N-dimethylarninopropyl-3 -azabicycloheptane (3 2:0)
10. As a novel composition of matter, the dimethonium chloride of N-dimethylaminopropyl-3-azabicycloheptane (3:2:0).
11. As a novel composition of matter, the dimethonium chloride of N-diethylaminoethyl 3 azabicycloheptane (3:2:0).
No references cited.
Claims (1)
1. AS A NOVEL COMPOSITION OF MATTER, A COMPOUND SELECTED FROM THE GROUP CONSISTING OF (1) COMPOUNDS HAVING THE FORMULA
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US539652A US2802003A (en) | 1955-10-10 | 1955-10-10 | Derivatives of 3-azabicycloheptane |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US539652A US2802003A (en) | 1955-10-10 | 1955-10-10 | Derivatives of 3-azabicycloheptane |
| CH813428X | 1955-10-10 |
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| Publication Number | Publication Date |
|---|---|
| US2802003A true US2802003A (en) | 1957-08-06 |
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| US539652A Expired - Lifetime US2802003A (en) | 1955-10-10 | 1955-10-10 | Derivatives of 3-azabicycloheptane |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2962496A (en) * | 1957-01-28 | 1960-11-29 | Geschickter Fund Med Res | Nu-substituted-3-azabicyclooctanes [3: 3: 0] and salts thereof |
| US3092630A (en) * | 1958-12-19 | 1963-06-04 | Gen Aniline & Film Corp | Preparation of nu-substituted-3-morpholones |
| US6871578B1 (en) * | 2000-08-24 | 2005-03-29 | Mitsubishi Denki Kaibushiki Kaisha | High-pressure fuel supply apparatus |
| US20050159474A1 (en) * | 2002-04-03 | 2005-07-21 | Astrazeneca Ab | Chemical compounds |
-
1955
- 1955-10-10 US US539652A patent/US2802003A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2962496A (en) * | 1957-01-28 | 1960-11-29 | Geschickter Fund Med Res | Nu-substituted-3-azabicyclooctanes [3: 3: 0] and salts thereof |
| US3092630A (en) * | 1958-12-19 | 1963-06-04 | Gen Aniline & Film Corp | Preparation of nu-substituted-3-morpholones |
| US6871578B1 (en) * | 2000-08-24 | 2005-03-29 | Mitsubishi Denki Kaibushiki Kaisha | High-pressure fuel supply apparatus |
| US20050159474A1 (en) * | 2002-04-03 | 2005-07-21 | Astrazeneca Ab | Chemical compounds |
| US7125906B2 (en) | 2002-04-03 | 2006-10-24 | Astrazeneca Ab | Indole derivatives having anti-angiogenetic activity |
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