JPS5829793B2 - Process for producing 7-alkoxycarbonyl-8-methylindolizino[1,2-b]quinolin-9(11H)-one - Google Patents
Process for producing 7-alkoxycarbonyl-8-methylindolizino[1,2-b]quinolin-9(11H)-oneInfo
- Publication number
- JPS5829793B2 JPS5829793B2 JP1592675A JP1592675A JPS5829793B2 JP S5829793 B2 JPS5829793 B2 JP S5829793B2 JP 1592675 A JP1592675 A JP 1592675A JP 1592675 A JP1592675 A JP 1592675A JP S5829793 B2 JPS5829793 B2 JP S5829793B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- quinolin
- alkoxycarbonyl
- methylindolizino
- producing
- 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
- 238000000034 method Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 8
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000060384 Mappia Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- WLXALCKAKGDNAT-UHFFFAOYSA-N diazoethane Chemical compound CC=[N+]=[N-] WLXALCKAKGDNAT-UHFFFAOYSA-N 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 229960004279 formaldehyde Drugs 0.000 description 1
- 235000019256 formaldehyde Nutrition 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 125000002496 methyl group Chemical class [H]C([H])([H])* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
【発明の詳細な説明】 本発明は次の一般式（Ｉ）。[Detailed description of the invention] The present invention relates to the following general formula (I).
（式中、Ｒは低級アルキル基を示す）で表わされる新規
な７−アルコキシカルボニル−８−メチルインドリジノ
〔１，２−ｂ〕キノリン−９（ＩＩＨ）−オンの製造法
に関する。The present invention relates to a method for producing a novel 7-alkoxycarbonyl-8-methylindolizino[1,2-b]quinolin-9(IIH)-one represented by the formula (wherein R represents a lower alkyl group).
而して、本発明の（Ｉ）式の化合物は近年Ｇｏｖｉｎｄ
ａｃｈａｒ ｉらによって天然のＭａｐｐｉａ ｆｏｅ
ｔｉｄａから単離された白血病および腫瘍に対して有効
な天然アルカロイドであるマピシンを合成するための中
間体として重要なものである。Therefore, the compound of formula (I) of the present invention has recently been developed by Govind
Natural Mappia foe by Achar I et al.
It is important as an intermediate for the synthesis of mapisin, a natural alkaloid effective against leukemia and tumors isolated from Tida.
本発明は先に合成した７−アルコキシカルボニルインド
リジノ［：１．２−ｂ、ｌキノリン−９（ＩＩＨ）−オ
ン（ＩＩ）を原料としてマピシンを合成せんと試みたが
、ピリドン環にメチル基を導入するのが困難であった。The present invention attempted to synthesize mapisin using the previously synthesized 7-alkoxycarbonyl indolizino[:1.2-b,l quinolin-9(IIH)-one (II)] as a raw material, but was difficult to introduce.
そこで、本発明者はこのメチル北について種々研究を行
った結果、（■）をジアゾメタンと反応せしめればメチ
ル化が行われるという新しいメチル化反応を見出し、本
発明を完成した。Therefore, the present inventor conducted various studies on this methyl north, and as a result, discovered a new methylation reaction in which methylation occurs when (■) is reacted with diazomethane, and completed the present invention.
すなわち、本発明は次の一般式（ＩＩ）
（式中、Ｒは前記と同じものを示す）で表わされる７−
アルコキシカルボニルインドリジノ〔１゜２−ｂ〕キノ
リン−９（１１Ｈ）−オン（ＩＩ）をジアゾメタンと反
応せしめて（１）式の化合物を製造する方法である。That is, the present invention provides a 7-
This is a method for producing a compound of formula (1) by reacting alkoxycarbonyl indolizino[1°2-b]quinolin-9(11H)-one (II) with diazomethane.
本発明方法を実施するには、（Ｉｆ）式の化合物をクロ
ロホルム、メタノール等の溶媒に溶かし、これに水冷下
過剰量のジアゾメタンを加え、約−昼夜室温に放置する
。To carry out the method of the present invention, the compound of formula (If) is dissolved in a solvent such as chloroform or methanol, an excess amount of diazomethane is added thereto under cooling with water, and the mixture is allowed to stand at room temperature for about 24 hours.
斯くするとき、（■）式の化合物と次の一般式（Ｉ）。In this case, a compound of formula (■) and the following general formula (I).
（式中、Ｒは前記と同じものを示す）で表わされる化合
物との混合物が得られるが、この混合物を例えばクロロ
ホルム−エーテルから再結晶すれば、（Ｉ）式の化合物
のみが晶出し、（１）式の化合物は母液に残るので、両
者を容易に分離することができる。(In the formula, R is the same as above.) A mixture is obtained, but if this mixture is recrystallized from, for example, chloroform-ether, only the compound of formula (I) is crystallized, and ( Since the compound of formula 1) remains in the mother liquor, the two can be easily separated.
以上の如くして得られる（１）式の化合物は、次の反応
式に従って、還元してアルコール体（１）となし、次い
でこれを酸化してアルデヒド体（７）となし、次いでこ
れにジアゾエタンを反応せしめてエチルケトン体（ロ）
となし、更にこれを還元してマピシン（イ）に導くこと
ができる。The compound of formula (1) obtained as described above is reduced to form alcohol (1) according to the following reaction formula, which is then oxidized to form aldehyde (7), which is then added to diazoethane. is reacted to produce ethyl ketone body (b)
This can then be further reduced to mapisin (a).
実施例
７−メドキシカルボニルインドリジノ〔１，２−ｂ）キ
ノリン−９（ＩＩＨ）−オン２グのクロロホルム５００
ｒｎｉ！とメタノール１００−の溶液に過剰のジアゾメ
タンのエーテル溶液（常法によってＮ−メチル−Ｎ−二
トロソ−Ｐ−１−ルエンスルホンアミド３０２から製し
た）を０℃で加え、その混合物を２４時間室温に放置し
た。Example 7 - Medoxycarbonyl indolizino[1,2-b)quinoline-9(IIH)-one 2g in chloroform 500
rni! An excess of an ethereal solution of diazomethane (prepared from N-methyl-N-nitroso-P-1-luenesulfonamide 302 by a conventional method) was added to a solution of 100- and methanol at 0°C, and the mixture was kept at room temperature for 24 hours. I left it there.
溶媒を減圧下留去し、残留物をクロロホルム−エーテル
から再結晶すれば、融点２５１〜２５３℃を示すプリズ
ム晶の７−メドキシカルボニルー８−メチルインドリジ
ノ〔１，２−ｂ）キノリン−９（１１Ｈ）オンＳＯＯ■
が得られた。When the solvent is distilled off under reduced pressure and the residue is recrystallized from chloroform-ether, a prismatic crystal of 7-medoxycarbonyl-8-methylindolizino[1,2-b)quinoline- 9 (11H) On SOO■
was gotten.
元素分析値Ｃｌ８Ｈ１４Ｎ２０３・１／４Ｈ２０理論値
［株］：Ｃ６９，５５、Ｈ４，５５、Ｈ９，０実測値（
ホ）：Ｃ６９，６，Ｈ４，５，Ｈ９，３５νｍａｘ（Ｋ
Ｂｒ）： １７２５ （ＣＯ□Ｍｅ） 、 １６５０（
ＣＯＮ （）ｃｍ ’Elemental analysis value Cl8H14N203・1/4H20 theoretical value [stock]: C69,55, H4,55, H9,0 actual value (
e): C69,6,H4,5,H9,35νmax(K
Br): 1725 (CO□Me), 1650 (
CON()cm'
Claims (1)
物をジアゾメタンと反応せしめることを特徴とする一般
式 （式中、Ｒは前記と同じものを示す）で表わされる７−
アルコキシカルボニル−８−メチルインドリジノ〔１，
２−ｂｌキノリン−９（ＩＩＨ）オンの製法。[Scope of Claims] General formula (1) characterized in that a compound represented by the general formula (in the formula, R represents a lower alkyl group) is reacted with diazomethane (in the formula, R represents the same as above) 7-
Alkoxycarbonyl-8-methylindolizino [1,
Method for producing 2-bl quinolin-9(IIH)one.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1592675A JPS5829793B2 (en) | 1975-02-07 | 1975-02-07 | Process for producing 7-alkoxycarbonyl-8-methylindolizino[1,2-b]quinolin-9(11H)-one |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1592675A JPS5829793B2 (en) | 1975-02-07 | 1975-02-07 | Process for producing 7-alkoxycarbonyl-8-methylindolizino[1,2-b]quinolin-9(11H)-one |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5191297A JPS5191297A (en) | 1976-08-10 |
| JPS5829793B2 true JPS5829793B2 (en) | 1983-06-24 |
Family
ID=11902373
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1592675A Expired JPS5829793B2 (en) | 1975-02-07 | 1975-02-07 | Process for producing 7-alkoxycarbonyl-8-methylindolizino[1,2-b]quinolin-9(11H)-one |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5829793B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6252687U (en) * | 1985-09-19 | 1987-04-01 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993020818A1 (en) * | 1990-10-31 | 1993-10-28 | Smithkline Beecham Corporation | SUBSTITUTED INDOLIZINO[1,2-b]QUINOLINONES |
| IE913790A1 (en) * | 1990-10-31 | 1992-05-22 | Smithkline Beecham Corp | SUBSTITUTED INDOLIZINO [1,2-b]QUINOLINONES |
| US5883255A (en) * | 1990-10-31 | 1999-03-16 | Smithkline Beecham Corporation | Substituted indolizino 1,2-b!quinolinones |
| WO1994025465A1 (en) * | 1993-05-03 | 1994-11-10 | Smithkline Beecham Corporation | SUBSTITUTED METHYLENEDIOXY[3',4':6,7]INDOLIZINO-[1,2-b]QUINOLINONES |
| FR2801309B1 (en) * | 1999-11-18 | 2002-01-04 | Adir | NOVEL CAMPTOTHECIN-LIKE COMPOUNDS, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
-
1975
- 1975-02-07 JP JP1592675A patent/JPS5829793B2/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6252687U (en) * | 1985-09-19 | 1987-04-01 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5191297A (en) | 1976-08-10 |
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