WO2005019223A1 - Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)­-1- piperidino]- carbonyloxycamptothecin - Google Patents

Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)­-1- piperidino]- carbonyloxycamptothecin Download PDF

Info

Publication number
WO2005019223A1
WO2005019223A1 PCT/CZ2004/000050 CZ2004000050W WO2005019223A1 WO 2005019223 A1 WO2005019223 A1 WO 2005019223A1 CZ 2004000050 W CZ2004000050 W CZ 2004000050W WO 2005019223 A1 WO2005019223 A1 WO 2005019223A1
Authority
WO
WIPO (PCT)
Prior art keywords
ethyl
piperidino
mol
hydroxycamptothecin
carbonyloxycamptothecin
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.)
Ceased
Application number
PCT/CZ2004/000050
Other languages
French (fr)
Inventor
Petr Dobrovolny
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pliva Lachema AS
Original Assignee
Pliva Lachema AS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Pliva Lachema AS filed Critical Pliva Lachema AS
Priority to EP04762302A priority Critical patent/EP1664054B1/en
Priority to DE602004024422T priority patent/DE602004024422D1/en
Priority to AT04762302T priority patent/ATE450539T1/en
Priority to HR20100112T priority patent/HRP20100112T1/en
Priority to PL04762302T priority patent/PL1664054T3/en
Priority to US10/567,472 priority patent/US7507825B2/en
Priority to AU2004266752A priority patent/AU2004266752A1/en
Publication of WO2005019223A1 publication Critical patent/WO2005019223A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis

Definitions

  • This invention relates to a method of manufacturing of 7-ethyl-10-[4-(l-piperidino)- -l-piperidino]-carbonyloxycamptothecin of formula I
  • the present invention relates to a method of manufacturing of 7-ethyl-10-[4-(l-piperidino)- -l-piperidino]-carbonyloxycamptothecin of formula I, characterized in that 7-ethyl- -10-hydroxycamptothecin of formula II
  • a polar aprotic solvent such as acetonitrile and in the presence of 4-dimethyl- aminopyridine.
  • the condensation proceeds in suspension, where the polar aprotic solvent dissolves only 4-dimethylaminopyridine whereas 7-ethyl-10-hydroxycamptothecin and l-chlorocarbonyl-4-piperidinopiperidine hydrochloride in this polar aprotic solvent remain undissolved.
  • the amount of l-chlorocarbonyl-4-piperidinopiperidine hydrochloride employed in the condensation reaction is preferably 1.3 to 3 mol, more preferably 1.6 to 1.9 mol, per 1 mol of 7-ethyl-10-hydroxycamptothecin.
  • the amount of 4-dimethylaminopyridine used in the condensation ranges preferably between 1.5 and 4 mol, more preferably between 1.8 and 2.2 mol, per 1 mol of 7-ethyl-lO-hydroxycamptothecin.
  • the amount of the polar aprotic solvent used in the condensation is preferably 400 to 600 mol, more preferably 430 to 460 mol, per mol of 7-ethyl-lO-hydroxycamptothecin.
  • the condensation is performed preferably at a temperature from 70 to 80 °C, more preferably at 73 to 77 °C.
  • the present ballast compounds consisting of e.g. 4-dimethylaminopyridine, 4-piperidinopiperidine and urea, are removed by washing of the obtained irinotecan base by a polar aprotic solvent, preferably acetonitrile.
  • the yield of the condensation is at least 94 % and the obtained product contains at least 98 % of the desired irinotecan base, as determined by high-performance liquid chromatography.
  • the main advantage of the method according to this invention consists in that the work-up of the reaction mixture after condensation proceeds only with negligible losses of the final product and that the condensation is not accompanied with coloured impurities.
  • the obtained solution is then added quantitatively to the suspension of 7-ethyl-10-hydroxy- camptothecin.
  • Into the empty beaker are then added 13.6 g (0.0434 mol) of 1-chlorocarbonyl- -4-piperidinopiperidine hydrochloride and 79 ml of acetonitrile and the suspension is stirred in the sonication bath until homogeneous.
  • the obtained suspension is transferred quantitatively into the three-necked Keller flask already containing 7 -ethyl- 10- hydroxycamptothecin and 4-dimethylaminopyridine in acetonitrile, and 382 ml of acetonitrile is added to the mixture.
  • the obtained reaction suspension in the Keller flask is stirred at 75 °C for 5 h. After 2 h the lightly yellow suspension becomes thicker and its colour turns into a coffee-white one, indicating thus correct course of the reaction. After 5 h, the suspension is cooled to 18 to 20 °C, filtered and the filtration cake is washed with 300 ml of acetonitrile. After removing the acetonitrile by suction filtration, the obtained 7-ethyl- -10-[4-(l-piperidino)-l-piperidino]-carbonyloxycamptothecin is dried at 60 to 65 °C to constant weight in a drier.

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oncology (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to the method of manufacturing of 7-ethyl-10-[4-(1-piperidino)­-1-piperidino]-carbonyloxycamptothecin by condensation of 7-ethyl-l0-hydroxycamptothecin with 1-chlorocarbonyl-4-piperidinopiperidine hydrochloride in a polar aprotic solvent in the presence of 4-dimethylaminopyridine.

Description

Method of Manufacturing of 7-Ethyl-10-[4-(l-piperidino)-l-piperidino]- -carbonyloxy camptothecin
Field of the Invention
This invention relates to a method of manufacturing of 7-ethyl-10-[4-(l-piperidino)- -l-piperidino]-carbonyloxycamptothecin of formula I
Figure imgf000002_0001
7-Ethyl-10-[4-(l-piperidino)-l-piperidino]-carbonyloxycamptothecin, which is also known as irinotecan base, is used for manufacturing of the cytostatically active irinotecan hydrochloride trihydrate, a topoisomerase inhibitor which is used in treatment of lung and rectum cancer.
Background of the Invention
7-Ethyl-10-[4-(l-piperidino)-l-piperidino]-carbonyloxycamptothecin has been hitherto prepared by condensation of 7-ethyl-lO-hydroxycamptothecin of formula
Figure imgf000002_0002
with l-chlorocarbonyl-4-piperidinopiperidine hydrochloride of formula
Figure imgf000003_0001
in pyridine at room temperature. This method of preparation has been described in US 4 604 463. However, this method of preparation of irinotecan base suffers from the fact that in the condensation coloured impurities are formed which have to be removed by adsorption on a silica gel column and subsequent recrystallization from ethanol. These purification steps are accompanied by substantial losses of the final product and its yields are only about 64 %. Moreover, the method requires distillation of pyridine, extraction of a chloroform layer with sodium carbonate and sodium chloride solutions, and drying of the chloroform layer over magnesium sulfate. Therefore, a better method of preparation of irinotecan base was needed. Such a goal has been achieved by the method according to the present invention.
Summary of the Invention
The present invention relates to a method of manufacturing of 7-ethyl-10-[4-(l-piperidino)- -l-piperidino]-carbonyloxycamptothecin of formula I, characterized in that 7-ethyl- -10-hydroxycamptothecin of formula II
Figure imgf000003_0002
is condensed with l-chlorocarbonyl-4-piperidinopiperidine hydrochloride of formula III
Figure imgf000004_0001
in a polar aprotic solvent such as acetonitrile and in the presence of 4-dimethyl- aminopyridine. The condensation proceeds in suspension, where the polar aprotic solvent dissolves only 4-dimethylaminopyridine whereas 7-ethyl-10-hydroxycamptothecin and l-chlorocarbonyl-4-piperidinopiperidine hydrochloride in this polar aprotic solvent remain undissolved. The amount of l-chlorocarbonyl-4-piperidinopiperidine hydrochloride employed in the condensation reaction is preferably 1.3 to 3 mol, more preferably 1.6 to 1.9 mol, per 1 mol of 7-ethyl-10-hydroxycamptothecin. The amount of 4-dimethylaminopyridine used in the condensation ranges preferably between 1.5 and 4 mol, more preferably between 1.8 and 2.2 mol, per 1 mol of 7-ethyl-lO-hydroxycamptothecin. The amount of the polar aprotic solvent used in the condensation is preferably 400 to 600 mol, more preferably 430 to 460 mol, per mol of 7-ethyl-lO-hydroxycamptothecin. The condensation is performed preferably at a temperature from 70 to 80 °C, more preferably at 73 to 77 °C.
After end of the condensation, the present ballast compounds, consisting of e.g. 4-dimethylaminopyridine, 4-piperidinopiperidine and urea, are removed by washing of the obtained irinotecan base by a polar aprotic solvent, preferably acetonitrile. The yield of the condensation is at least 94 % and the obtained product contains at least 98 % of the desired irinotecan base, as determined by high-performance liquid chromatography.
The main advantage of the method according to this invention consists in that the work-up of the reaction mixture after condensation proceeds only with negligible losses of the final product and that the condensation is not accompanied with coloured impurities. Examples
Example 1
Into a beaker in a sonication bath are placed 10 g (0.0247 mol) of 7-ethyl-10-hydroxy- camptothecin and 99 ml of acetonitrile. The obtained suspension is stirred in the sonication bath to homogeneity. Then the suspension is transferred quantitatively into a three-necked Keller flask equipped with a mechanical stirrer, thermometer and reflux condenser. Into the now empty beaker are now placed 6.2 g (0.0502 mol) of crystalline 4-dimethylaminopyridine and 40 ml of acetonitrile. The mixture is stirred until the crystalline portion dissolves. The obtained solution is then added quantitatively to the suspension of 7-ethyl-10-hydroxy- camptothecin. Into the empty beaker are then added 13.6 g (0.0434 mol) of 1-chlorocarbonyl- -4-piperidinopiperidine hydrochloride and 79 ml of acetonitrile and the suspension is stirred in the sonication bath until homogeneous. The obtained suspension is transferred quantitatively into the three-necked Keller flask already containing 7 -ethyl- 10- hydroxycamptothecin and 4-dimethylaminopyridine in acetonitrile, and 382 ml of acetonitrile is added to the mixture. The obtained reaction suspension in the Keller flask is stirred at 75 °C for 5 h. After 2 h the lightly yellow suspension becomes thicker and its colour turns into a coffee-white one, indicating thus correct course of the reaction. After 5 h, the suspension is cooled to 18 to 20 °C, filtered and the filtration cake is washed with 300 ml of acetonitrile. After removing the acetonitrile by suction filtration, the obtained 7-ethyl- -10-[4-(l-piperidino)-l-piperidino]-carbonyloxycamptothecin is dried at 60 to 65 °C to constant weight in a drier. This affords 14.1 g (yield 94.3 %) of product which, according to high-performance liquid chromatography, contains 98.9 % of 7-ethyl-10-[4-(l-piperidino)- -l-piperidino]-carbonyloxycamptothecin.

Claims

PATENT CLAIMS
1. A method of manufacturing of 7-ethyl-10-[4-(l-piperidino)-l-piperidino]-carbonyloxy- camptothecin of formula I
Figure imgf000006_0001
characterized in that 7-ethyl-lO-hydroxycamptothecin of formula π
Figure imgf000006_0002
is subjected to a condensation reaction with ϊ-chlorocarbonyl-4-piperidinopiperidine hydrochloride of formula III
Figure imgf000006_0003
in a polar aprotic solvent, e.g. in acetonitrile, in the presence of 4-dimethylaminopyridine.
2. The method according to claim 1, characterized in that 1-chlorocarbonyl- -4-piperidinopiperidine hydrochloride is employed in an amount of 1.3 to 3 mol, preferably in an amount of 1.6 to 1.9 mol, per 1 mol of 7-ethyl-lO-hydroxycamptothecin.
3. The method according to any of the preceding claims, characterized in that 4-dimethylaminopyridine is employed in an amount of 1.5 to 4 mol, preferably in an amount of 1.8 to 2.2 mol, per 1 mol of 7-ethyl-lO-hydroxycamptothecin.
4. The method according to any of the preceding claims, characterized in that the polar aprotic solvent is employed in an amount of 400 to 600 mol, preferably in an amount of 430 to 460 mol, per 1 mol of 7-ethyl-lO-hydroxycamptothecin.
5. The method according to any of the preceding claims, characterized in that the condensation reaction is carried out at a temperature of 70 to 80 °C, preferably at a temperature of 73 to 77 °C.
PCT/CZ2004/000050 2003-08-26 2004-08-24 Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)­-1- piperidino]- carbonyloxycamptothecin Ceased WO2005019223A1 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
EP04762302A EP1664054B1 (en) 2003-08-26 2004-08-24 Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin
DE602004024422T DE602004024422D1 (en) 2003-08-26 2004-08-24 PROCESS FOR THE PREPARATION OF 7-ETHYL-10-AE4- (1-PIPERIDINO) -1-PIPERIDINOU-CARBONYLOXYCAMPTOTHECIN
AT04762302T ATE450539T1 (en) 2003-08-26 2004-08-24 METHOD FOR PRODUCING 7-ETHYL-10-Ä4-(1-
HR20100112T HRP20100112T1 (en) 2003-08-26 2004-08-24 7-ETHYL-10 [4-1-PIPERIDINO) -1-PIPERIDINO] CARBONYLOXYCAMPTOTECIN PREPARATION PROCEDURE
PL04762302T PL1664054T3 (en) 2003-08-26 2004-08-24 Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin
US10/567,472 US7507825B2 (en) 2003-08-26 2004-08-24 Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)-1- piperidino]- carbonyloxy- camptothecin
AU2004266752A AU2004266752A1 (en) 2003-08-26 2004-08-24 Method of manufacturing of 7-ethyl-10-(4-(1-piperidino)--1- piperidino)- carbonyloxycamptothecin

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CZ20032305A CZ299329B6 (en) 2003-08-26 2003-08-26 Process for preparing 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy camptothecin
CZPV2003-2305 2003-08-26

Publications (1)

Publication Number Publication Date
WO2005019223A1 true WO2005019223A1 (en) 2005-03-03

Family

ID=34201062

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CZ2004/000050 Ceased WO2005019223A1 (en) 2003-08-26 2004-08-24 Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)­-1- piperidino]- carbonyloxycamptothecin

Country Status (11)

Country Link
US (1) US7507825B2 (en)
EP (1) EP1664054B1 (en)
AT (1) ATE450539T1 (en)
AU (1) AU2004266752A1 (en)
CZ (1) CZ299329B6 (en)
DE (1) DE602004024422D1 (en)
ES (1) ES2337578T3 (en)
HR (1) HRP20100112T1 (en)
PL (1) PL1664054T3 (en)
RU (1) RU2334748C2 (en)
WO (1) WO2005019223A1 (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1803725A1 (en) 2005-12-13 2007-07-04 W.C. Heraeus GmbH Methods for preparing irinotecan
US7507825B2 (en) 2003-08-26 2009-03-24 Pliva-Lachema A.S. Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)-1- piperidino]- carbonyloxy- camptothecin
US7544801B2 (en) 2003-12-16 2009-06-09 Pliva-Lachema A.S. Method of manufacturing of 7-ethyl-10-hydroxycamptothecin
EP2341046A3 (en) * 2009-11-18 2011-08-24 Cadila Healthcare Limited Process for the preparation of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin hydrochloride trihydrate
CN102260272A (en) * 2011-08-12 2011-11-30 扬子江药业集团有限公司 Method for preparing irinotecan hydrochloride
CN102627653A (en) * 2012-03-20 2012-08-08 南京臣功制药股份有限公司 Preparation method of irinotecan hydrochloride
EP2881396A1 (en) * 2013-12-03 2015-06-10 Synbias Pharma AG Method for the synthesis of irinotecan
CN113811535A (en) * 2019-05-16 2021-12-17 台湾神隆股份有限公司 Polymorphism of irinotecan free base

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012032531A1 (en) * 2010-09-06 2012-03-15 Avra Laboratories Pvt. Ltd. Process for the manufacture of irinotecan hydrochloride by total synthesis

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4604463A (en) * 1983-07-14 1986-08-05 Kabushiki Kaisha Yakult Honsha Camptothecin derivatives and process for preparing same
WO1996031513A1 (en) * 1995-04-07 1996-10-10 Pharmacia & Upjohn Company Novel intermediates and process for the manufacture of camptothecin derivatives (cpt-11) and related compounds

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3894029A (en) * 1971-08-26 1975-07-08 Basf Ag Production of camptothecin and camptothecin-like compounds
JPS5198300A (en) * 1975-02-20 1976-08-30 Kanputoteshin oyobi sonoruijitaino seizoho
US4399282A (en) * 1979-07-10 1983-08-16 Kabushiki Kaisha Yakult Honsha Camptothecin derivatives
US4383431A (en) 1980-11-03 1983-05-17 The Perkin-Elmer Corporation Auto-zero system for pressure transducers
US4399276A (en) * 1981-01-09 1983-08-16 Kabushiki Kaisha Yakult Honsha 7-Substituted camptothecin derivatives
JPS5839685A (en) 1981-09-04 1983-03-08 Yakult Honsha Co Ltd Novel camptothecin derivative and its preparation
US4473692A (en) * 1981-09-04 1984-09-25 Kabushiki Kaisha Yakult Honsha Camptothecin derivatives and process for preparing same
JPS58154582A (en) 1982-03-10 1983-09-14 Yakult Honsha Co Ltd Novel camptothecin derivative and its preparation
FR2560442B1 (en) 1984-02-24 1987-08-07 Thomson Csf SLOT LINE SWITCHING AND LIMITING DEVICE, OPERATING IN MICROWAVE
FR2560315B1 (en) 1984-02-29 1990-05-18 Dba AUTOMATIC GAME RETRIEVAL DEVICE FOR CLUTCH
JPS6150984A (en) * 1984-07-05 1986-03-13 Yakult Honsha Co Ltd Novel camptothecin derivative
CA1332413C (en) * 1987-06-25 1994-10-11 Kabushiki Kaisha Yakult Honsha Camptothecin derivatives and process for preparing same
JPH0615547B2 (en) * 1988-01-20 1994-03-02 株式会社ヤクルト本社 Novel camptothecin derivative
FI931384A7 (en) * 1990-09-28 1993-03-26 Smithkline Beecham Corp Water-soluble camptothecin analogs, processes and methods
GB9402934D0 (en) * 1994-02-16 1994-04-06 Erba Carlo Spa Camptothecin derivatives and process for their preparation
US5491237A (en) * 1994-05-03 1996-02-13 Glaxo Wellcome Inc. Intermediates in pharmaceutical camptothecin preparation
JPH0873461A (en) * 1994-09-06 1996-03-19 Yakult Honsha Co Ltd Novel camptothecin derivative, its production method and antitumor agent
ES2180063T3 (en) * 1996-12-19 2003-02-01 Reddys Lab Ltd Dr ANALOGS OF 20 (S) -CAMPTOTECINA IN RING C SOLUBLES IN WATER.
JP4094710B2 (en) * 1997-11-06 2008-06-04 株式会社ヤクルト本社 New camptothecin derivatives
AU4564200A (en) * 1999-04-29 2000-11-17 Aventis Pharma S.A. Method for treating cancer using camptothecin derivatives and 5-fluorouracil
AR027687A1 (en) * 2000-03-22 2003-04-09 Yakult Honsha Kk PROCEDURE TO PREPARE CAMPTOTECHINE
AR035684A1 (en) * 2001-02-21 2004-06-23 Yakult Honsha Kk PROCEDURE TO PREPARE 2'-AMINO-5'-HYDROXYPROPIOPHENONE, USE OF THE SAME FOR THE PREPARATION OF CAMPTOTECHINE ANALOGS, PROCEDURE TO PREPARE THEM, INTERMEDIATE COMPOUNDS, PROCEDURE TO PREPARE A TRICYCLINT KITONE USED IN THE CAMP
CZ20022250A3 (en) * 2002-06-27 2004-02-18 Pliva-Lachema A. S. Method for producing irinotecan
US7151179B2 (en) * 2003-05-12 2006-12-19 Scinopharm Taiwan, Ltd. Process for the preparation of 7-alkyl-10-hydroxy-20(S)-camptothecin
CZ299329B6 (en) 2003-08-26 2008-06-18 Pliva-Lachema A.S. Process for preparing 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy camptothecin
CZ299593B6 (en) 2003-12-16 2008-09-10 Pliva-Lachema A. S. Process for preparing 7-ethyl-10-hydroxycamptothecine
US20050272757A1 (en) * 2004-06-04 2005-12-08 Phytogen Life Sciences Inc. Process to prepare camptothecin derivatives and novel intermediate and compounds thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4604463A (en) * 1983-07-14 1986-08-05 Kabushiki Kaisha Yakult Honsha Camptothecin derivatives and process for preparing same
WO1996031513A1 (en) * 1995-04-07 1996-10-10 Pharmacia & Upjohn Company Novel intermediates and process for the manufacture of camptothecin derivatives (cpt-11) and related compounds
US6235907B1 (en) * 1995-04-07 2001-05-22 Pharmacia & Upjohn Company Intermediates useful in making mappicine and related compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SAWADA S ET AL: "SYNTHESIS AND ANTITUMOR ACTIVITY OF 20(S)-CAMPTOTHECIN DERIVATIVES:CARBAMATE-LINKED, WATER-SOLUBLE DERIVATIVES OF 7-ETHYL-10-HYDROXYCAMPTOTHECIN", CHEMICAL AND PHARMACEUTICAL BULLETIN, PHARMACEUTICAL SOCIETY OF JAPAN. TOKYO, JP, vol. 39, no. 6, 1 June 1991 (1991-06-01), pages 1446 - 1454, XP000653715, ISSN: 0009-2363 *

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7507825B2 (en) 2003-08-26 2009-03-24 Pliva-Lachema A.S. Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)-1- piperidino]- carbonyloxy- camptothecin
US7544801B2 (en) 2003-12-16 2009-06-09 Pliva-Lachema A.S. Method of manufacturing of 7-ethyl-10-hydroxycamptothecin
US8039626B2 (en) 2003-12-16 2011-10-18 Plus Chemicals Sa Method of manufacturing of 7-ethyl-10-hydroxycamptothecin
EP1803725A1 (en) 2005-12-13 2007-07-04 W.C. Heraeus GmbH Methods for preparing irinotecan
US7683170B2 (en) 2005-12-13 2010-03-23 W. C. Heraeus Gmbh Methods for preparing Irinotecan
EP2341046A3 (en) * 2009-11-18 2011-08-24 Cadila Healthcare Limited Process for the preparation of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin hydrochloride trihydrate
CN102260272A (en) * 2011-08-12 2011-11-30 扬子江药业集团有限公司 Method for preparing irinotecan hydrochloride
CN102260272B (en) * 2011-08-12 2016-01-13 扬子江药业集团有限公司 A kind of method preparing U 101440E
CN102627653B (en) * 2012-03-20 2014-10-29 南京臣功制药股份有限公司 Preparation method of irinotecan hydrochloride
CN102627653A (en) * 2012-03-20 2012-08-08 南京臣功制药股份有限公司 Preparation method of irinotecan hydrochloride
EP2881396A1 (en) * 2013-12-03 2015-06-10 Synbias Pharma AG Method for the synthesis of irinotecan
WO2015082240A1 (en) * 2013-12-03 2015-06-11 Synbias Pharma Ag Method for the synthesis of irinotecan
JP2016539107A (en) * 2013-12-03 2016-12-15 シンバイアス ファーマ アー・ゲー Method for synthesizing irinotecan
US9765083B2 (en) 2013-12-03 2017-09-19 Synbias Pharma Ag Method for the synthesis of irinotecan
KR101813423B1 (en) 2013-12-03 2017-12-28 신바이어스 파마 아게 Method for the synthesis of irinotecan
RU2648989C2 (en) * 2013-12-03 2018-03-29 Синбиас Фарма АГ Method for the synthesis of irinotecan
CN113811535A (en) * 2019-05-16 2021-12-17 台湾神隆股份有限公司 Polymorphism of irinotecan free base
JP2022536591A (en) * 2019-05-16 2022-08-18 サイノファーム タイワン，リミティド Polymorph of irinotecan free base

Also Published As

Publication number Publication date
ATE450539T1 (en) 2009-12-15
ES2337578T3 (en) 2010-04-27
CZ20032305A3 (en) 2005-04-13
AU2004266752A1 (en) 2005-03-03
EP1664054A1 (en) 2006-06-07
RU2334748C2 (en) 2008-09-27
EP1664054B1 (en) 2009-12-02
US7507825B2 (en) 2009-03-24
HRP20100112T1 (en) 2010-12-31
US20060199961A1 (en) 2006-09-07
PL1664054T3 (en) 2010-06-30
CZ299329B6 (en) 2008-06-18
DE602004024422D1 (en) 2010-01-14
RU2006109481A (en) 2006-07-27

Similar Documents

Publication Publication Date Title
JP5827407B2 (en) Process for producing 4- [5- (pyridin-4-yl) -1H-1,2,4-triazol-3-yl] pyridine-2-carbonitrile and intermediate
Liao et al. 12-N-Methylated 5, 6-dihydrobenzo [c] acridine derivatives: A new class of highly selective ligands for c-myc G-quadruplex DNA
WO2005019223A1 (en) Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)­-1- piperidino]- carbonyloxycamptothecin
JP2005507900A (en) Citalopram manufacturing method
CN115710257B (en) Sulfate crystal form of an amide compound, pharmaceutical composition and use thereof
CN106905319B (en) The preparation method of substituted benzenesulfonyl matrine or its hydrochloride
EP0964865B1 (en) Pharmaceutically active tricyclic amines
CN104277059A (en) A kind of preparation method of fluoroquinolone antibiotics
EP2139899B1 (en) Crystalline forms of topotecan hydrochloride and processes for making the same
CN118955485A (en) Crystal form, pharmaceutical composition and use of a compound
CN113563340B (en) A kind of matrine pyrimidine derivative and its preparation method and application
CN110724108B (en) Esalapril Lin Zhongjian body and preparation method thereof
CN114933601A (en) Tetrandrine derivatives and preparation method and application thereof
JPH07121931B2 (en) Benzo [b] furan derivative
US5240947A (en) 2,3,4,5-substituted furo[2,3-c]pyrazole derivatives
CN114621155A (en) Method for preparing carbamatinib
CN114989163A (en) Praziquantel synthesis process
CN110746361B (en) Esalapril Lin Zhongjian body and preparation method thereof
CN108610342B (en) A new class of azanopolycyclic compounds and their preparation methods and applications
CN110724135B (en) Esalapril Lin Zhongjian body and preparation method thereof
KR100453379B1 (en) Method for preparing piperidine derivatives
CN110818694B (en) Esalapu Lin Zhongjian body and application thereof
AU2004326111A1 (en) Process for preparing 5,6-dihydro-4-(S)-(ethylamino)-6-(S) methyl-4H-thieno[2,3b]thiopyran-2-sulphonamide-7,7-dioxide HCI
JPH05306284A (en) Indoloquinoline derivative
WO2012032531A1 (en) Process for the manufacture of irinotecan hydrochloride by total synthesis

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DPEN Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed from 20040101)
WWE Wipo information: entry into national phase

Ref document number: 10567472

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 2004266752

Country of ref document: AU

ENP Entry into the national phase

Ref document number: 2004266752

Country of ref document: AU

Date of ref document: 20040824

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2004762302

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2006109481

Country of ref document: RU

WWP Wipo information: published in national office

Ref document number: 2004762302

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 10567472

Country of ref document: US