JPH034075B2 - - Google Patents
Info
- Publication number
- JPH034075B2 JPH034075B2 JP58065208A JP6520883A JPH034075B2 JP H034075 B2 JPH034075 B2 JP H034075B2 JP 58065208 A JP58065208 A JP 58065208A JP 6520883 A JP6520883 A JP 6520883A JP H034075 B2 JPH034075 B2 JP H034075B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- ether
- group
- mixture
- fluoromethyl
- 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
- -1 4'-Fluoromethyl-3-amino-2 -Methyl-substituted propiophenone Chemical class 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- ZULYWMQOPPBKAG-UHFFFAOYSA-N 1-[4-(fluoromethyl)phenyl]propan-1-one Chemical compound CCC(=O)C1=CC=C(CF)C=C1 ZULYWMQOPPBKAG-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000002329 infrared spectrum Methods 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 235000019256 formaldehyde Nutrition 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical class CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003759 ester based solvent Substances 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 1
- MMWLPFRDTCOCAY-UHFFFAOYSA-N 1-[4-(bromomethyl)phenyl]propan-1-one Chemical compound CCC(=O)C1=CC=C(CBr)C=C1 MMWLPFRDTCOCAY-UHFFFAOYSA-N 0.000 description 1
- QKENZCSQLKSMHR-UHFFFAOYSA-N 1-[4-(fluoromethyl)phenyl]-2-methyl-3-pyrrolidin-1-ylpropan-1-one Chemical compound C=1C=C(CF)C=CC=1C(=O)C(C)CN1CCCC1 QKENZCSQLKSMHR-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- PATYHUUYADUHQS-UHFFFAOYSA-N 4-methylpropiophenone Chemical compound CCC(=O)C1=CC=C(C)C=C1 PATYHUUYADUHQS-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010061619 Deformity Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 208000003618 Intervertebral Disc Displacement Diseases 0.000 description 1
- 206010050296 Intervertebral disc protrusion Diseases 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000023178 Musculoskeletal disease Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 206010041591 Spinal osteoarthritis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229920005565 cyclic polymer Polymers 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- 125000004971 nitroalkyl group Chemical group 0.000 description 1
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 208000005801 spondylosis Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は新規な4′−フルオロメチル−3−アミ
ノ−2−メチル置換プロピオフエノン誘導体、及
びその薬理学的に許容しうる酸付加塩に関するも
のである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel 4'-fluoromethyl-3-amino-2-methyl substituted propiophenone derivatives and pharmacologically acceptable acid addition salts thereof.
更に詳しく言えば、本発明は一般式()
(式中、基Aは、ピロリジノ基、ピペリジノ基
又はモルホリノ基を表わす。)
で示される新規な4′−フルオロメチル−3−アミ
ノ−2−メチル置換プロピオフエノン誘導体、及
びその薬理学的に許容しうる酸付加塩に関するも
のである。 More specifically, the present invention relates to the general formula () (In the formula, group A represents a pyrrolidino group, a piperidino group or a morpholino group.) A novel 4'-fluoromethyl-3-amino-2-methyl substituted propiophenone derivative represented by Concerning acceptable acid addition salts.
本発明の前記一般式()で示される化合物
は、所望に応じて薬理学的に許容しうる酸付加塩
に変換することも、又は生成した酸付加塩から、
塩基を遊離させることもできる。 The compound represented by the general formula () of the present invention can be converted into a pharmacologically acceptable acid addition salt as desired, or from the generated acid addition salt,
It is also possible to liberate the base.
本発明の前記一般式()で示される化合物の
薬理学的に許容しうる酸付加塩としては、たとえ
ば、塩酸、硝酸、硫酸、臭化水素酸、ヨウ化水素
酸、燐酸等の鉱酸塩、あるいは、酢酸、マレイン
酸、フマール酸、クエン酸、シユウ酸、酒石酸等
の有機酸塩が挙げられる。 Examples of the pharmacologically acceptable acid addition salts of the compound represented by the general formula () of the present invention include mineral acid salts such as hydrochloric acid, nitric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, and phosphoric acid. , or organic acid salts such as acetic acid, maleic acid, fumaric acid, citric acid, oxalic acid, and tartaric acid.
本発明の前記一般式()で示される新規な
4′−フルオロメチル−3−アミノ−2−メチル置
換プロピオフエノン誘導体は、次の式()
で示される4′−フルオロメチルプロピオフエノン
に、溶媒中ホルムアルデヒド類及び、次の一般式
()
H−A ()
(式中、基Aは前述と同意義を表わす。)
で示されるアミン化合物もしくはその塩類を、そ
れ自体公知の方法(マンニツヒ反応)で反応させ
ることにより製造される。 The novel compound represented by the above general formula () of the present invention
The 4'-fluoromethyl-3-amino-2-methyl substituted propiophenone derivative has the following formula () 4'-fluoromethylpropiophenone, formaldehyde in a solvent, and an amine compound represented by the following general formula () H-A () (wherein, group A has the same meaning as above) Alternatively, it is produced by reacting salts thereof using a method known per se (Mannitzsch reaction).
使用されるホルムアルデヒド類としては、ホル
ムアルデヒド、又はその線状もしくは環状重合体
であるバラホルムアルデヒド、トリオキサン等が
挙げられる。 Examples of formaldehydes used include formaldehyde, its linear or cyclic polymers paraformaldehyde, trioxane, and the like.
アミン化合物は、通常、塩酸、臭化水素酸、硝
酸等の鉱酸塩として使用するが、遊離のアミン化
合物を使用するときは、反応系が充分酸性となる
に足る鉱酸を加えて行うことにより実施できる。 Amine compounds are usually used as mineral acid salts such as hydrochloric acid, hydrobromic acid, nitric acid, etc., but when using free amine compounds, sufficient mineral acid should be added to make the reaction system sufficiently acidic. It can be implemented by
反応当量比は適宜選択しうるが、特に反応後の
処理において残留するアミン化合物を消失させる
必要から、前記一般式()で示されるアミン化
合物1当量に対して、前記式()で示される
4′−フルオロメチルプロピオフエノンの少なくと
も1当量以上、好ましくは1.1当量と、ホルムア
ルデヒド類の少なくとも1当量以上、好ましくは
1.5当量とを反応せしめることである。 Although the reaction equivalent ratio can be selected as appropriate, it is necessary to eliminate the amine compound remaining in the post-reaction treatment, so the reaction equivalent ratio is 1 equivalent of the amine compound represented by the general formula () to 1 equivalent of the amine compound represented by the general formula ().
At least 1 equivalent, preferably 1.1 equivalent, of 4'-fluoromethylpropiophenone and at least 1 equivalent, preferably formaldehyde.
1.5 equivalents.
反応に際して用いられる溶媒としては、メタノ
ール、エタノール、プロパノールイソプロパノー
ル等のアルコール系溶媒、ニトロメタン、ニトロ
エタン等のニトロアルカン系溶媒、酢酸メチル、
酢酸エチル、プロピオン酸エチル等の低級脂肪酸
低級アルキルエステル系溶媒を挙げることがで
き、特に低級脂肪酸低級アルキルエステル系溶媒
を使用することが好ましい。 Solvents used in the reaction include alcohol solvents such as methanol, ethanol, propanol and isopropanol, nitroalkane solvents such as nitromethane and nitroethane, methyl acetate,
Examples include lower fatty acid lower alkyl ester solvents such as ethyl acetate and ethyl propionate, and it is particularly preferable to use lower fatty acid lower alkyl ester solvents.
反応は室温から加熱還流下において行われ、特
に好ましくは使用する溶媒の還流温度下において
行うことである。 The reaction is carried out at room temperature to reflux, particularly preferably at the reflux temperature of the solvent used.
尚、本発明の方法において出発原料となつた前
記式()で示される4′−フルオロメチルプロピ
オフエノンも又、新規な化合物であり、その製造
については参考例に記載した。 Incidentally, 4'-fluoromethylpropiophenone represented by the above formula (), which is a starting material in the method of the present invention, is also a new compound, and its production is described in Reference Examples.
この様にして製造される前記一般式()で示
される新規な4′−フルオロメチル−3−アミノ−
2−メチル置換プロピオンフエノン誘導体、及び
その薬理学的に許容しうる酸付加塩は、優れた筋
弛緩、脊髄反射抑制、抗痙攣作用等を有してお
り、腰背痛、椎間板ヘルニア、変形性脊椎症等の
運動器疾患に伴う有痛性筋痙縮の治療剤として極
めて有用である。 The novel 4'-fluoromethyl-3-amino- represented by the general formula () produced in this way
2-Methyl-substituted propionphenone derivatives and their pharmacologically acceptable acid addition salts have excellent muscle relaxation, spinal reflex suppression, anticonvulsant effects, etc., and are effective against lower back pain, intervertebral disc herniation, and deformity. It is extremely useful as a therapeutic agent for painful muscle spasms associated with musculoskeletal diseases such as spondylosis.
以下、本発明を実施例によつて説明する。 Hereinafter, the present invention will be explained with reference to Examples.
参考例 1
4′−ブロモメチルプロピオフエノン
4′−メチルプロピオフエノン43.4gに、四塩化
炭素240ml、N−ブロモコハク酸イミド0.50g及
び過酸化ベンゾイル0.50gを加え、1時間加熱還
流する。冷後、反応混合物を過する。液は減
圧乾固し、得られた残渣に90%含水エタノールを
加える。析出物を取して、表記化合物29.37g
を得る。イソプロピルエーテルから再結晶して、
融点58〜59゜の無色板状晶を得る。Reference Example 1 4'-Bromomethylpropiophenone 240 ml of carbon tetrachloride, 0.50 g of N-bromosuccinimide and 0.50 g of benzoyl peroxide were added to 43.4 g of 4'-methylpropiophenone, and the mixture was heated under reflux for 1 hour. After cooling, the reaction mixture is filtered. The liquid is dried under reduced pressure, and 90% aqueous ethanol is added to the resulting residue. Collect the precipitate and obtain 29.37g of the listed compound.
get. Recrystallized from isopropyl ether,
Colorless platelet crystals with a melting point of 58-59° are obtained.
IRスペクトル ν(KBr)cm-1:
1685(C=0)
元素分析値 C10H11BrO
理論値 C,52.89;H,4.88
実験値 C,52.71;H,5.07
参考例 2
4′−フルオロメチルプロピオフエノン
参考例1で得た4′−ブロモメチルプロピオフエ
ノン35.0gに、フツ化カリウム44.6g及びジエチ
レングリコール80mlを加え、140゜にて1時間加熱
撹拌する。冷後、反応液に水を加え、エーテルに
抽出する。エーテル層は水洗、脱水。溶媒を留去
する。得られた残渣を減圧蒸留し、沸点100〜
101゜(6mmHg)の無色液体として表記化合物13.3
gを得る。 IR spectrum ν (KBr) cm -1 : 1685 (C=0) Elemental analysis value C 10 H 11 BrO Theoretical value C, 52.89; H, 4.88 Experimental value C, 52.71; H, 5.07 Reference example 2 4'-Fluoromethyl Propiophenone 44.6 g of potassium fluoride and 80 ml of diethylene glycol were added to 35.0 g of 4'-bromomethylpropiophenone obtained in Reference Example 1, and the mixture was heated and stirred at 140° for 1 hour. After cooling, water was added to the reaction mixture, and the mixture was extracted with ether. The ether layer is washed with water and dehydrated. The solvent is distilled off. The obtained residue is distilled under reduced pressure, and the boiling point is 100~
Compound 13.3 described as a colorless liquid at 101° (6 mmHg)
get g.
IRスペクトル ν(film)cm-1:
1690(C=0)
実施例 1
4′−フルオロメチル−2−メチル−3−ピペリ
ジノプロピオフエノン
参考例2で得た4′−フルオロメチルプロピオフ
エノン4.98gのイソプロパノール10ml溶液に、ピ
ペリジン、塩酸塩3.52g及びパラホルムアルデヒ
ド1.35gを加え、4時間加熱還流する。反応後溶
媒を留去し、残渣に塩酸水溶液を加えて抽出し、
水層を分取する。水層をエーテルでぱ洗浄後、炭
酸カリウムにてアルカリ性となし、エーテル抽出
する。エーテル層は水洗、脱水。溶媒を留去し、
得られた残渣をエーテルに溶解後、15%エタノー
ル性塩酸を加える。析出結晶を取する。取物
をエタノール及びエーテルの混液から再結晶し、
融点172〜173゜の無色針状晶として表記化合物の
塩酸塩3.05gを得る。 IR spectrum ν (film) cm -1 : 1690 (C=0) Example 1 4'-Fluoromethyl-2-methyl-3-piperidinopropiofenone 4'-Fluoromethylpropioff obtained in Reference Example 2 To a solution of 4.98 g of enone in 10 ml of isopropanol are added piperidine, 3.52 g of hydrochloride, and 1.35 g of paraformaldehyde, and the mixture is heated under reflux for 4 hours. After the reaction, the solvent was distilled off, and the residue was extracted with an aqueous hydrochloric acid solution.
Separate the aqueous layer. After washing the aqueous layer with ether, it is made alkaline with potassium carbonate and extracted with ether. The ether layer is washed with water and dehydrated. Distill the solvent,
After dissolving the resulting residue in ether, 15% ethanolic hydrochloric acid is added. Take the precipitated crystals. The sample was recrystallized from a mixture of ethanol and ether,
3.05 g of the hydrochloride salt of the title compound are obtained as colorless needles with a melting point of 172-173°.
IRスペクトル ν(KBr)cm-1:
1680(C=0)
元素分析値 C16H22FNO・HCl
理論値 C,64.10;H,7.73;N,4.67
実験値 C,64.11;H,7.63;N,4.66
実施例 2
4′−フルオロメチル−2−メチル−3−ピロリ
ジノプロピオフエノン
参考例2で得た4′−フルオロメチルプロピオフ
エノン4.00gの酢酸エチルエステル15ml溶液に、
ピロリジン・塩酸塩2.50g、パラホルムアルデヒ
ド1.10g及び22%酢酸エチルエステル性塩酸0.5
mlを加え、4時間加熱還流する。反応後、塩酸水
溶液を加えて振とうし、水層を分取する。水層は
炭酸カリウムにてアルカリ性となし、エーテル抽
出する。エーテル層は水洗、脱水。溶媒を留去
し、得られた残渣をエーテルに溶解後、40%エタ
ノール性塩酸を加える。析出結晶を取する。
取物をエタノール及びエーテルの混液から再結晶
し、融点151〜152゜の無色板状晶として表記化合
物の塩酸塩3.20gを得る。 IR spectrum ν (KBr) cm -1 : 1680 (C=0) Elemental analysis value C 16 H 22 FNO・HCl Theoretical value C, 64.10; H, 7.73; N, 4.67 Experimental value C, 64.11; H, 7.63; N , 4.66 Example 2 4'-Fluoromethyl-2-methyl-3-pyrrolidinopropiophenone To a solution of 4.00 g of 4'-fluoromethylpropiophenone obtained in Reference Example 2 in 15 ml of ethyl acetate,
Pyrrolidine hydrochloride 2.50g, paraformaldehyde 1.10g and 22% acetic acid ethyl ester hydrochloric acid 0.5g
ml and heated under reflux for 4 hours. After the reaction, add an aqueous hydrochloric acid solution, shake, and separate the aqueous layer. The aqueous layer is made alkaline with potassium carbonate and extracted with ether. The ether layer is washed with water and dehydrated. After evaporating the solvent and dissolving the resulting residue in ether, 40% ethanolic hydrochloric acid is added. Take the precipitated crystals.
The residue was recrystallized from a mixture of ethanol and ether to give 3.20 g of the hydrochloride of the title compound as colorless plate crystals with a melting point of 151-152°.
IRスペクトル ν(KBr)cm-1:
1680(C=0)
元素分析値 C15H20FNO・HCl
理論値 C,63.04;H,7.41;N,4.90
実験値 C,63.16;H,7.49;N,4.94
実施例 3
4′−フルオロメチル−2−メチル−3−モルホ
リノプロピオフエノン
参考例2で得た4′−フルオロメチルプロピオフ
エノン4.50gの酢酸エチルエステル20ml溶液に、
モルホリン2.20g及びパラホルムアルデヒド1.20
gを加える。次いで、冷却撹拌下、塩化水素ガス
を導入し酸性となし、4時間加熱還流する。以下
実施例2と同様に処理し、表記化合物の塩酸塩
3.71gを得る。エタノール及びエーテルの混液か
ら再結晶して、融点157〜158゜の無色針状晶を得
る。 IR spectrum ν (KBr) cm -1 : 1680 (C=0) Elemental analysis value C 15 H 20 FNO・HCl Theoretical value C, 63.04; H, 7.41; N, 4.90 Experimental value C, 63.16; H, 7.49; N , 4.94 Example 3 4'-Fluoromethyl-2-methyl-3-morpholinopropiophenone Into a 20 ml solution of 4.50 g of 4'-fluoromethylpropiophenone obtained in Reference Example 2 in ethyl acetate,
Morpholine 2.20g and paraformaldehyde 1.20
Add g. Next, while cooling and stirring, hydrogen chloride gas was introduced to make the mixture acidic, and the mixture was heated under reflux for 4 hours. The hydrochloride of the title compound was then treated in the same manner as in Example 2.
Obtain 3.71g. Recrystallization from a mixture of ethanol and ether gives colorless needles with a melting point of 157-158°.
IRスペクトル ν(KBr)cm-1: 1680(C=0) 元素分析値 C15H20FNO2・HCl 理論値 C,59.70;H,7.01;N,4.64 実験値 C,59.84;H,7.14;N,4.59 IR spectrum ν (KBr) cm -1 : 1680 (C=0) Elemental analysis value C 15 H 20 FNO 2・HCl Theoretical value C, 59.70; H, 7.01; N, 4.64 Experimental value C, 59.84; H, 7.14; N, 4.59
Claims (1)
又はモルホリノ基を表わす。) で示される4′−フルオロメチル−3−アミノ−2
−メチル置換プロピオフエノン誘導体、及びその
薬理学的に許容しうる酸付加塩。[Claims] 1. General formula (In the formula, the group A represents a pyrrolidino group, a piperidino group or a morpholino group.) 4'-Fluoromethyl-3-amino-2
-Methyl-substituted propiophenone derivatives and pharmacologically acceptable acid addition salts thereof.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP58065208A JPS59190982A (en) | 1983-04-15 | 1983-04-15 | 4'-fluoromethyl-3-amino-2-methyl-substituted propiophenone derivative |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP58065208A JPS59190982A (en) | 1983-04-15 | 1983-04-15 | 4'-fluoromethyl-3-amino-2-methyl-substituted propiophenone derivative |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS59190982A JPS59190982A (en) | 1984-10-29 |
JPH034075B2 true JPH034075B2 (en) | 1991-01-22 |
Family
ID=13280261
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP58065208A Granted JPS59190982A (en) | 1983-04-15 | 1983-04-15 | 4'-fluoromethyl-3-amino-2-methyl-substituted propiophenone derivative |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS59190982A (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999001420A1 (en) * | 1997-07-03 | 1999-01-14 | Taito Co., Ltd. | Process for the preparation of 2-aminomalonic acid derivatives and intermediates used in the process |
-
1983
- 1983-04-15 JP JP58065208A patent/JPS59190982A/en active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS59190982A (en) | 1984-10-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4265894A (en) | Piperazine derivatives | |
US3801636A (en) | 3,4,5-tri-substituted cinnamides | |
JPS601300B2 (en) | Method for producing tertiary amine | |
JPH10152460A (en) | 2-amino-1-(4-hydroxy-2-methylphenyl)propanol derivative | |
SU845777A3 (en) | Method of preparing cis-4a-phenyl-2,3,4a,5,6,7,7a-octahydro-1h-2-pyridines | |
JPH034075B2 (en) | ||
JPS6356223B2 (en) | ||
JPH0517443A (en) | Piperidine derivative | |
JPS649993B2 (en) | ||
JPS5933276A (en) | 3-pyrrolidino substituted propiophenone derivative | |
JPS6225666B2 (en) | ||
JPS59190980A (en) | 2'-chloro-3-amino-2-methyl-substituted propiophenone derivative | |
JPH0534351B2 (en) | ||
JP4234206B2 (en) | Method for preparing tetrahydropyridine derivatives | |
JP2604589B2 (en) | Method for producing imidazolidine derivative | |
JPS60169461A (en) | 2-methoxyphenylpiperazine derivative | |
JPH026483A (en) | Novel isoxazole derivative and central muscle relaxant containing the same derivative as active ingredient | |
JPS6155496B2 (en) | ||
JPS59190981A (en) | 3-pyrrolidino-substituted propiophenone derivative | |
JP4441260B2 (en) | Process for producing 4-amino-4-phenylpiperidines | |
JPH0550495B2 (en) | ||
JPS6363546B2 (en) | ||
JPS5922708B2 (en) | Manufacturing method of indazole derivatives | |
JPH0550517B2 (en) | ||
JPH05271220A (en) | Amine derivatives and hypotensor containing the same |