JPS6330304B2 - - Google Patents
Info
- Publication number
- JPS6330304B2 JPS6330304B2 JP8284782A JP8284782A JPS6330304B2 JP S6330304 B2 JPS6330304 B2 JP S6330304B2 JP 8284782 A JP8284782 A JP 8284782A JP 8284782 A JP8284782 A JP 8284782A JP S6330304 B2 JPS6330304 B2 JP S6330304B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- nitrobenzaldehyde
- methyl
- reacting
- acetoacetate
- 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
Links
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- HBVWZQCLPFPSCF-UHFFFAOYSA-N 2-hydroxyethyl 3-oxobutanoate Chemical compound CC(=O)CC(=O)OCCO HBVWZQCLPFPSCF-UHFFFAOYSA-N 0.000 claims description 3
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 claims description 3
- XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 claims description 3
- 125000004925 dihydropyridyl group Chemical class N1(CC=CC=C1)* 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- -1 Benzylidene acetoacetate derivatives Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 210000001105 femoral artery Anatomy 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 210000002385 vertebral artery Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- PAWSVPVNIXFKOS-IHWYPQMZSA-N (Z)-2-aminobutenoic acid Chemical class C\C=C(/N)C(O)=O PAWSVPVNIXFKOS-IHWYPQMZSA-N 0.000 description 1
- SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 description 1
- JAEUQHNZRROYID-UHFFFAOYSA-N 2-chloroethyl 3-oxobutanoate Chemical compound CC(=O)CC(=O)OCCCl JAEUQHNZRROYID-UHFFFAOYSA-N 0.000 description 1
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 238000003445 Hantzsch reaction Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000978776 Senegalia senegal Species 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 description 1
- 150000004729 acetoacetic acid derivatives Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- RLKBOGLIOLFMEK-NSCUHMNNSA-N amino (e)-but-2-enoate Chemical compound C\C=C\C(=O)ON RLKBOGLIOLFMEK-NSCUHMNNSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 229940085304 dihydropyridine derivative selective calcium channel blockers with mainly vascular effects Drugs 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- DGEYTDCFMQMLTH-UHFFFAOYSA-N methanol;propan-2-ol Chemical compound OC.CC(C)O DGEYTDCFMQMLTH-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical class OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Description
【発明の詳細な説明】
Ａ 産業上の利用分野
本発明は式
で表わされるジヒドロピリジン誘導体の新規な製
造法に関する。
本発明の製造法による化合物はそれ自体優れ
た抗高血圧作用、血管拡張作用を有している。さ
らに他の１，４―ジヒドロピリジン誘導体合成の
ための中間体としても極めて有用である。
Ｂ 従来の技術と問題点
ベンジリデンアセトアセテート誘導体およびβ
―アミノクロトネート誘導体、あるいはベンジリ
デンアセトアセテート、アセトアセテート誘導体
およびアンモニアを反応させることにより、２，
６―ジメチル―４―フエニル―１，４―ジヒドロ
ピリジン―３，５―ジカルボキシレート誘導体を
合成する反応はHantzsch反応と呼ばれ、その変
法と共に広く知られている〔たとえば、Ann.、
215、１（1882）；Ber.、15、2914（1882）、17、
1521（1884）、17、2903（1884）、20、1338（1887）、
31、743（1898）；J.Chem.Soc.、413（1943）；J.
Amer.Chem.Soc.、71、4003（1949）；J.Org.
Chem.、30、1914（1965）などを参照。〕
一方、水酸基は多くの反応において、反応に活
性であり、またその極性のために取り扱い難いな
どの点から、通常水酸基を保護基で保護して、あ
るいは水酸基に変換しうる基をつけて反応が行わ
れ、最後に水酸基に導かれる場合が多い。化合物
は特開昭58−167570、58−167571号および
Arzneim.―Forsch.、33、106（1983）に記載され
ている。製造法はArzneim.―Forsch.、33、106
（1983）に記載されているが、水酸基の代わりに
塩素原子で閉環反応が行われ、塩素原子をアセト
キシ基に変換し、ついでアセトキシ基を加水分解
して水酸基に導かれている。すなわち、下記に示
すルートに従つて合成されている。
この方法によると３―ニトロベンズアルデヒド
からの収率はわずかに14％に過ぎない。しかも２
―クロロエチル アセトアセテートおよびこの原
料となるエチレンクロルヒドリンは刺激性であ
り、取り扱い等に特別の注意を払わなければなら
ない。
また化合物の原料となつている２―アセトキ
シエチル メチル１，４―ジヒドロ―２，６―ジ
メチル―４―（３―ニトロフエニル）―３，５―
ビリジンカルボキシレート（上記化合物）の別
途合成法も知られている〔たとえば、ドイツ公開
特許、第2847236号（1980）などを参照〕。すなわ
ち下記の方法である。
しかしながら、この方法においても化合物の
原料となる化合物の収率は40％であり、３―ニ
トロベンズアルデヒドより１行程で得られるメチ
ル ２―（３―ニトロフエニルメチリデン）アセ
トアセテートからの化合物への通算収率は27％
に過ぎない。
Ｃ 問題を解決するための手段および作用
本発明者らは、この様な現状をふまえ、鋭意研
究を重ねた結果、本発明を完成するに至つた。
化合物は次の方法に従い容易に製造すること
ができる。すなわち、過剰のエチレングリコール
に塩基（たとえば、水素化ナトリウム、ナトリウ
ムエトキシド、トリエチルアミンなど）存在下、
ジケテンを反応させ、生成した２―ヒドロキシエ
チル アセトアセテートを単離して、あるいは単
離することなく、さらに３―ニトロベンズアルデ
ヒドおよびメチル３―アミノクロトネートを反応
させて化合物を得ることができる。本製造方法
での化合物の収率は極めて良好で３―ニトロベ
ンズアルデヒドからの収率は57％である。
Ｄ 実施例
実施例 １
エチレングリコール120mlに50％水素化ナトリ
ウムム50mgを加え、さらにジケテン20ｇを徐々に
滴下。ついで水浴上３時間加熱。この混合物に３
―ニトロベンズアルデヒド32ｇおよびメチルβ―
アミノクロトネート24ｇを加え、よく混合した
後、さらに５時間水浴上で加熱。ついで放冷する
と結晶析出。結晶をろ取し、イソプロピルアルコ
ールにて洗浄、乾燥して２―ヒドロキシエチル
メチル１，４―ジヒドロ―２，６―ジメチル―４
―（３―ニトロフエニル）―３，５―ピリジン
ジカルボキシレートの淡黄色プリズム晶（45ｇ、
収率57％）を得た。メタノール―イソプロピルア
ルコールより再結晶して、淡黄色針状晶、mp176
〜178゜を得た。
NMR（CDCl3）δ：2.00（1H、br）、2.39（6H、
ｓ）、3.65（3H、ｓ）、3.63〜4.00（2H、ｍ）、4.10
（2H、ｍ）、5.14（1H、ｓ）、6.06（1H、br）、7.23
〜8.20（4H、ｍ）。
NMR（CD3OD）δ：2.40（6H、ｓ）、3.68（3H、
ｓ）、3.67〜3.95（2H、ｍ）、4.07〜4.33（2H、ｍ）、
5.16（1H、ｓ）、7.30〜8.23（4H、ｍ）。
実施例 ２
椎骨および大腿動脈血流におよぼす作用
犬をベントバルビタールナトリウム（30mg／
Kg、iv）にて麻酔し、人工呼吸下に、椎骨および
大腿動脈血流量を電磁流量計にて測定した。また
同時に血圧も測定した。被験薬は、ポリエチレン
グリコールに溶解し、さらに生理食塩水で希釈し
た後大腿静脈内に投与した。結果は第１表に示し
た。
【表】
実施例 ３
急性毒性
体重22〜26ｇのddY系雄性マウスを用いた。被
験薬はアラビアゴム末と共に懸濁して経口投与し
た。LD50値は投与１週間後の致死数よりBehrens
―Karber法にて求めた。
結果は第２表に示した。
【表】
Ｅ 効果
化合物は、それ自体優れた薬理特性を有して
いる。さらに他の生理活性物質合成のための中間
体としても有用である。
本発明によれば、化合物を極めて容易に、し
かも好収率で製造することができる。故に本発明
は産業上極めて有用である。 [Detailed description of the invention] A. Industrial application field The present invention is based on the formula This invention relates to a novel method for producing dihydropyridine derivatives represented by: The compound produced by the production method of the present invention itself has excellent antihypertensive and vasodilatory effects. Furthermore, it is extremely useful as an intermediate for the synthesis of other 1,4-dihydropyridine derivatives. B. Conventional technology and problems Benzylidene acetoacetate derivatives and β
-By reacting an aminocrotonate derivative, or benzylidene acetoacetate, an acetoacetate derivative, and ammonia, 2,
The reaction for synthesizing 6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate derivatives is called the Hantzsch reaction, and its modifications are widely known [for example, Ann.
215, 1 (1882); Ber., 15 , 2914 (1882), 17 ,
1521 (1884), 17 , 2903 (1884), 20 , 1338 (1887),
31, 743 (1898); J.Chem.Soc., 413 (1943); J.
Amer.Chem.Soc., 71 , 4003 (1949); J.Org.
Chem., 30 , 1914 (1965), etc. On the other hand, in many reactions, hydroxyl groups are active in reactions and difficult to handle due to their polar nature, so hydroxyl groups are usually protected with a protecting group or attached with a group that can be converted into a hydroxyl group. is carried out, and the final step is often led to a hydroxyl group. The compound is disclosed in JP-A-58-167570, 58-167571 and
Arzneim.—Forsch., 33 , 106 (1983). The manufacturing method is Arzneim.--Forsch., 33 , 106.
(1983), a ring-closing reaction is performed with a chlorine atom instead of a hydroxyl group, the chlorine atom is converted to an acetoxy group, and the acetoxy group is then hydrolyzed to become a hydroxyl group. That is, it is synthesized according to the route shown below. According to this method, the yield from 3-nitrobenzaldehyde is only 14%. And 2
-Chloroethyl acetoacetate and its raw material, ethylene chlorohydrin, are irritating and must be handled with special care. Also, 2-acetoxyethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-, which is a raw material for the compound.
Separate methods for synthesizing pyridine carboxylates (the above compounds) are also known (see, for example, German Published Patent Application No. 2847236 (1980)). That is, the following method is used. However, even with this method, the yield of the compound that is the raw material for the compound is 40%, and the yield of the compound from methyl 2-(3-nitrophenyl methylidene) acetoacetate obtained in one step from 3-nitrobenzaldehyde is 40%. Total yield is 27%
It's nothing more than that. C. Means and Effects for Solving the Problems The present inventors have completed the present invention as a result of extensive research based on the current situation. The compound can be easily produced according to the following method. That is, in the presence of a base (e.g., sodium hydride, sodium ethoxide, triethylamine, etc.) in excess ethylene glycol,
The compound can be obtained by reacting diketene and isolating the produced 2-hydroxyethyl acetoacetate, or by further reacting 3-nitrobenzaldehyde and methyl 3-aminocrotonate without isolation. The yield of the compound in this production method is extremely good, and the yield from 3-nitrobenzaldehyde is 57%. D Examples Example 1 50 mg of 50% sodium hydride was added to 120 ml of ethylene glycol, and 20 g of diketene was gradually added dropwise. Then heat it on a water bath for 3 hours. Add 3 to this mixture
-32g of nitrobenzaldehyde and methyl β-
Add 24 g of aminocrotonate, mix well, and heat on a water bath for an additional 5 hours. Then, when it is allowed to cool, crystals precipitate. The crystals were collected by filtration, washed with isopropyl alcohol, and dried to give 2-hydroxyethyl
Methyl 1,4-dihydro-2,6-dimethyl-4
-(3-nitrophenyl)-3,5-pyridine
Pale yellow prismatic crystals of dicarboxylate (45g,
A yield of 57% was obtained. Recrystallized from methanol-isopropyl alcohol to give pale yellow needle crystals, mp176
~178° was obtained. NMR ( CDCl3 ) δ: 2.00 (1H, br), 2.39 (6H,
s), 3.65 (3H, s), 3.63-4.00 (2H, m), 4.10
(2H, m), 5.14 (1H, s), 6.06 (1H, br), 7.23
~8.20 (4H, m). NMR (CD 3 OD) δ: 2.40 (6H, s), 3.68 (3H,
s), 3.67-3.95 (2H, m), 4.07-4.33 (2H, m),
5.16 (1H, s), 7.30-8.23 (4H, m). Example 2 Effects on vertebral and femoral artery blood flow Dogs were treated with bentobarbital sodium (30mg/
The animals were anesthetized at 100 kg, iv), and vertebral and femoral artery blood flow was measured using an electromagnetic flowmeter under artificial respiration. Blood pressure was also measured at the same time. The test drug was dissolved in polyethylene glycol, further diluted with physiological saline, and then administered into the femoral vein. The results are shown in Table 1. [Table] Example 3 Acute Toxicity Male ddY mice weighing 22 to 26 g were used. The test drug was suspended with gum arabic powder and administered orally. The LD 50 value was calculated from the number of fatalities one week after administration.
- Obtained using the Karber method. The results are shown in Table 2. [Table] E Effect The compound itself has excellent pharmacological properties. Furthermore, it is useful as an intermediate for the synthesis of other physiologically active substances. According to the present invention, compounds can be produced extremely easily and in good yields. Therefore, the present invention is extremely useful industrially.
Claims (1)
３―ニトロベンズアルデヒドおよびメチル３―ア
ミノクロトネートを反応させることを特徴とする
式 で表わされるジヒドロピリジン誘導体の製造法。 ２ 過剰のエチレングリコールにジケテンを作用
させて得られる２―ヒドロキシエチル アセトア
セテートを、単離することなく、過剰のエチレン
グリコールを溶媒として、３―ニトロベンズアル
デヒドおよびメチル ３―アミノクロトネートを
反応させることを特徴とする式 で表わされるジヒドロピリジン誘導体の製造法。[Claims] 1. A formula characterized by reacting 2-hydroxyethyl acetoacetate with 3-nitrobenzaldehyde and methyl 3-aminocrotonate. A method for producing a dihydropyridine derivative represented by 2. Reacting 2-hydroxyethyl acetoacetate obtained by reacting diketene with excess ethylene glycol with 3-nitrobenzaldehyde and methyl 3-aminocrotonate using excess ethylene glycol as a solvent without isolating it. An expression characterized by A method for producing a dihydropyridine derivative represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8284782A JPS58201764A (en) | 1982-05-17 | 1982-05-17 | Dihydropyridine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8284782A JPS58201764A (en) | 1982-05-17 | 1982-05-17 | Dihydropyridine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58201764A JPS58201764A (en) | 1983-11-24 |
| JPS6330304B2 true JPS6330304B2 (en) | 1988-06-17 |
Family
ID=13785770
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8284782A Granted JPS58201764A (en) | 1982-05-17 | 1982-05-17 | Dihydropyridine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58201764A (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2230746C2 (en) | 1999-06-14 | 2004-06-20 | Орто-Макнейл Фармасьютикал, Инк. | Derivatives of dithiepino[6,5-b]pyridine, methods for their preparing, pharmaceutical composition based on thereof and methods for inhibition and treatment of disorders |
| CA2379199A1 (en) | 1999-07-12 | 2001-01-18 | Ortho-Mcneil Pharmaceutical, Inc. | Oxathiepino[6,5-b]dihydropyridines, and related compositions and methods |
| US6472530B1 (en) | 1999-09-22 | 2002-10-29 | Ortho-Mcneil Pharmaceutical, Inc. | Benzo-fused dithiepino[6,5-b]pyridines, and related compositions and methods |
| AU2001261161A1 (en) | 2000-05-30 | 2001-12-11 | Ortho-Mcneil Pharmaceutical, Inc. | Dihydropyridine compounds for inhibition of calcium-influx |
| CN100420673C (en) | 2002-09-11 | 2008-09-24 | 韩林制药株式会社 | S-(-)-amlodipine nicotinate and process for the preparation thereof |
| JP5637710B2 (en) * | 2010-03-24 | 2014-12-10 | 株式会社トクヤマ | {2-Amino-1,4-dihydro-6-methyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid 3- (1-diphenylmethylazetidin-3-yl) ester 5-isopropyl ester } Manufacturing method |
-
1982
- 1982-05-17 JP JP8284782A patent/JPS58201764A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58201764A (en) | 1983-11-24 |
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