JP2003524625A - 新規プロセス - Google Patents
新規プロセスInfo
- Publication number
- JP2003524625A JP2003524625A JP2000612269A JP2000612269A JP2003524625A JP 2003524625 A JP2003524625 A JP 2003524625A JP 2000612269 A JP2000612269 A JP 2000612269A JP 2000612269 A JP2000612269 A JP 2000612269A JP 2003524625 A JP2003524625 A JP 2003524625A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- acid
- hexamethyldisilazide
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 11
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical group [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 claims description 7
- XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 claims description 5
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- FWUQWDCOOWEXRY-ZDUSSCGKSA-N lanicemine Chemical compound C([C@H](N)C=1C=CC=CC=1)C1=CC=CC=N1 FWUQWDCOOWEXRY-ZDUSSCGKSA-N 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 230000003197 catalytic effect Effects 0.000 claims description 3
- KRCGPQRORHRZRC-SXWHKFHYSA-N (2s)-2-hydroxybutanedioic acid;(1s)-1-phenyl-2-pyridin-2-ylethanamine Chemical compound OC(=O)[C@@H](O)CC(O)=O.C([C@H](N)C=1C=CC=CC=1)C1=CC=CC=N1 KRCGPQRORHRZRC-SXWHKFHYSA-N 0.000 claims description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 4
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-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
- DZAIOXUZHHTJKN-UHFFFAOYSA-N 2-Desoxy-D-glycero-tetronsaeure Natural products OCC(O)CC(O)=O DZAIOXUZHHTJKN-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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229940049920 malate Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- -1 (S) -α-phenyl-2-pyridineethanamine (S) -malate lithium Chemical compound 0.000 description 1
- FWUQWDCOOWEXRY-UHFFFAOYSA-N 1-phenyl-2-pyridin-2-ylethanamine Chemical compound C=1C=CC=CC=1C(N)CC1=CC=CC=N1 FWUQWDCOOWEXRY-UHFFFAOYSA-N 0.000 description 1
- NMWDYLYNWRFEMR-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1.CC1=CC=CC=N1 NMWDYLYNWRFEMR-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 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
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 208000006011 Stroke 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
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Abstract
Description
化合物を開示している。(S)−1−フェニル−2−(2−ピリジル)エタンアミン
は、特に卒中の治療にとって、格別に興味深いものである。しかしながら、この
化合物の合成のためにEP 0 633 879 B1で開示された方法は、例えば、大規模で
の使用には不便なブチルリチウムの使用を要するといったある種の不利益がある
。
(S)−1−フェニル−2−(2−ピリジル)エタンアミンの合成のための新規プロ
セスが開発された。本発明の方法ではブチルリチウムを使用する必要がないので
、ブタン排出に関連した環境問題で悩まないという付加的な利点も有する。さら
に、驚くべきことに本発明の方法は、EP 0 633 879 B1において使用されるよう
な化学量論量の塩基[式(II)の2−ピコリンに関して]よりもむしろ、触媒量の
塩基だけで進行し得ることが判明した。総じて、請求された製造方法は、EP 0 6
33 879 B1のそれよりも、それゆえより効率的で、安全で、環境保全に配慮した
もので、安価である。
その後に化合物(I)のエナンチオマーを分割することおよび薬学的に許容される
塩を形成することを含む、式(I):
好ましくはリチウムヘキサメチルジシラジド(LHMDS)から合成され得る。好
ましくは式(III)の化合物は低温で、つまり35℃以下、好ましくは25℃以下
で合成される。
る。該反応は、不活性溶媒、好ましくはt−ブチルメチルエーテル、さらに好ま
しくはテトラヒドロフランのようなエーテル系溶媒中で行われる。好ましくは、
金属ヘキサメチルジシラジドはリチウムヘキサメチルジシラジド(LHMDS)で
あり、この塩基は式(II)の2−ピコリン(2−メチルピリジン)に対して触媒量、
例えば約10mol%で使用される。反応液を酸性の後処理をすると、式(I)の所望
の化合物を得る。
)の化合物は、慣習的で薬学的に許容される酸、例えばリンゴ酸、塩酸、臭化水
素酸、リン酸、酢酸、フマル酸、サリチル酸、クエン酸、乳酸、マンデル酸、酒
石酸、トリフルオロ酢酸およびメタンスルホン酸といった酸で酸付加塩を形成し
得る。好ましい塩は、リンゴ酸塩および塩酸塩である。
の単一のエナンチオマー塩を与えるキラル酸を用いて合成され得るものである。
好ましくは式(I)のラセミ化合物は、(S)−リンゴ酸で処理され、(S)−1−フ
ェニル−2−(2−ピリジル)エタンアミン (S)−リンゴ酸塩を与える。
1−フェニル−2−(2−ピリジル)エタンアミンおよびその塩、特に(S)−リン
ゴ酸塩を提供する。
1.1mol)を窒素雰囲気下、冷却しながら、テトラヒドロフラン(305ml)中のベンズ
アルデヒド(102ml、1.0mol)の溶液に、撹拌下、25℃以下に温度を保ちながら
滴下した。得られた溶液を20℃で30分間撹拌した後、2−ピコリン(101ml、
1.0mol)を一度に加え、続いてさらにテトラヒドロフラン(102ml)を加えた。その
後、反応液を30分間かけて40℃まで加熱し、その後90分間40℃に保持し
た。その後、その溶液を10分かけて20℃まで冷却し、濃塩酸(420ml、5.0mol
)の脱塩水(900ml)溶液に、温度を10から20℃の間に保つように冷却しながら
滴下した。得られた混合物(pH1)を20℃で15分間撹拌すると、層が分離し
た。下の水層を分離し、酢酸エチル(2x900ml)で洗浄し、その後、温度を10か
ら20℃の範囲に保つように冷却しながら、水酸化ナトリウム(200g、5.0mol)の
脱塩水(830ml)溶液の添加によって塩基性化した。その後、得られた溶液(pH1
2)を20℃で15分間撹拌し、次いで酢酸エチル(2x800ml)で抽出した。該酢
酸エチル溶液を(S)−リンゴ酸(120.7g、0.9mol)のエタノール(1060ml)溶液に加
え、続いて表題の化合物の種晶(0.2g)を加えた。この混合液を20℃で30分
間撹拌し、その後、0℃まで冷却し、0℃で20時間撹拌した。その懸濁液をろ
過し、エタノール(530ml)で洗浄すると、白色固体を得、バキュームオーブン中
40℃で一夜乾燥すると、白色固体として(S)−α−フェニル−2−ピリジンエ
タンアミン (S)−リンゴ酸塩(119.07g、35.8%)を得、既知物質と一致した。
Claims (7)
- 【請求項1】 式(II): 【化1】 の化合物と式(III): 【化2】 の化合物を、金属ヘキサメチルジシラジド存在下において反応させ、所望により
その後に化合物(I)のエナンチオマーを分割することおよび薬学的に許容される
塩を形成することを含む、式(I): 【化3】 の化合物または薬学的に許容されるその塩の製造方法。 - 【請求項2】 金属ヘキサメチルジシラジドがリチウムヘキサメチルジシラ
ジドである、請求項1記載の方法。 - 【請求項3】 化合物(II)および(III)をエーテル系溶媒中で反応させる、
請求項1または請求項2記載の方法。 - 【請求項4】 リチウムヘキサメチルジシラジドが式(II)の化合物に対して
触媒量で使用される、請求項1から3までのいずれかに記載の方法。 - 【請求項5】 化合物(II)とリチウムヘキサメチルジシラジドのモル比が約
10:1である、請求項1から4までのいずれかに記載の方法。 - 【請求項6】 請求項1から5までのいずれかに記載の方法によって合成さ
れた、(S)−1−フェニル−2−(2−ピリジル)エタンアミンまたはその塩。 - 【請求項7】 請求項1から5までのいずれかに記載の方法によって合成さ
れた、(S)−1−フェニル−2−(2−ピリジル)エタンアミン (S)−リンゴ酸
塩
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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SE9901340A SE9901340D0 (sv) | 1999-04-15 | 1999-04-15 | Novel process |
SE9901340-1 | 1999-04-15 | ||
PCT/SE2000/000713 WO2000063175A2 (en) | 1999-04-15 | 2000-04-14 | Novel process |
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JP2003524625A true JP2003524625A (ja) | 2003-08-19 |
JP2003524625A5 JP2003524625A5 (ja) | 2007-05-10 |
JP4676064B2 JP4676064B2 (ja) | 2011-04-27 |
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JP2000612269A Expired - Fee Related JP4676064B2 (ja) | 1999-04-15 | 2000-04-14 | 新規プロセス |
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US (1) | US6518432B1 (ja) |
EP (1) | EP1492769B1 (ja) |
JP (1) | JP4676064B2 (ja) |
KR (1) | KR100663811B1 (ja) |
CN (1) | CN1138759C (ja) |
AT (1) | ATE333444T1 (ja) |
AU (1) | AU773962B2 (ja) |
BR (1) | BR0009795B1 (ja) |
CA (1) | CA2367410C (ja) |
DE (1) | DE60029493T2 (ja) |
ES (1) | ES2267526T3 (ja) |
IL (2) | IL145585A0 (ja) |
NO (1) | NO320810B1 (ja) |
NZ (1) | NZ514586A (ja) |
SE (1) | SE9901340D0 (ja) |
TW (1) | TWI248433B (ja) |
WO (1) | WO2000063175A2 (ja) |
ZA (1) | ZA200108374B (ja) |
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UA106056C2 (uk) | 2008-12-24 | 2014-07-25 | Астразенека Аб | Сполуки 2-метил-1-феніл-2-(піридин-2-іл)пропан-1-аміну та їх застосування для лікування депресії |
CA2928004C (en) | 2013-11-05 | 2022-04-12 | Astrazeneca Ab | Nmda antagonist prodrugs |
Citations (1)
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JPH08508292A (ja) * | 1993-04-01 | 1996-09-03 | アストラ・アクチエボラーグ | (S)−α−フェニル−2−ピリジンエタンアミン(S)−マレートおよび医薬としてのその使用 |
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US5455259A (en) * | 1987-02-06 | 1995-10-03 | Fisons Corporation | Compounds for the treatment of neurodegenerative disorders |
PT612314E (pt) * | 1991-10-30 | 2000-06-30 | Astra Ab | Derivados de etilamina 2-heterociclicos e seu uso como produtos farmaceuticos |
KR100259567B1 (ko) | 1992-04-03 | 2000-07-01 | 클래스 빌헬름슨 | 신경변성 질환 치료용 1-페닐-2-(2-피리디닐)에틸아민 에난티오머 |
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1999
- 1999-04-15 SE SE9901340A patent/SE9901340D0/xx unknown
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2000
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JPH08508292A (ja) * | 1993-04-01 | 1996-09-03 | アストラ・アクチエボラーグ | (S)−α−フェニル−2−ピリジンエタンアミン(S)−マレートおよび医薬としてのその使用 |
Also Published As
Publication number | Publication date |
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WO2000063175A2 (en) | 2000-10-26 |
EP1492769A2 (en) | 2005-01-05 |
AU773962B2 (en) | 2004-06-10 |
KR20010113799A (ko) | 2001-12-28 |
BR0009795B1 (pt) | 2011-12-27 |
CN1370145A (zh) | 2002-09-18 |
NO320810B1 (no) | 2006-01-30 |
DE60029493T2 (de) | 2007-01-11 |
NZ514586A (en) | 2003-09-26 |
ATE333444T1 (de) | 2006-08-15 |
KR100663811B1 (ko) | 2007-01-03 |
CA2367410A1 (en) | 2000-10-26 |
SE9901340D0 (sv) | 1999-04-15 |
JP4676064B2 (ja) | 2011-04-27 |
ES2267526T3 (es) | 2007-03-16 |
CN1138759C (zh) | 2004-02-18 |
NO20014889D0 (no) | 2001-10-08 |
IL145585A (en) | 2006-12-31 |
BR0009795A (pt) | 2002-01-08 |
US6518432B1 (en) | 2003-02-11 |
ZA200108374B (en) | 2003-08-06 |
AU4444700A (en) | 2000-11-02 |
NO20014889L (no) | 2001-10-08 |
TWI248433B (en) | 2006-02-01 |
WO2000063175A3 (en) | 2004-11-11 |
EP1492769B1 (en) | 2006-07-19 |
IL145585A0 (en) | 2002-11-10 |
CA2367410C (en) | 2009-08-11 |
DE60029493D1 (de) | 2006-08-31 |
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