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WO2001092254A1 - Procede permettant de remplacer des solvants contenus dans des cristaux de type clathrates - Google Patents

Procede permettant de remplacer des solvants contenus dans des cristaux de type clathrates Download PDF

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Publication number
WO2001092254A1
WO2001092254A1 PCT/JP2001/004467 JP0104467W WO0192254A1 WO 2001092254 A1 WO2001092254 A1 WO 2001092254A1 JP 0104467 W JP0104467 W JP 0104467W WO 0192254 A1 WO0192254 A1 WO 0192254A1
Authority
WO
WIPO (PCT)
Prior art keywords
crystal
crystals
clathrate
organic solvent
acetone
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/JP2001/004467
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English (en)
Japanese (ja)
Inventor
Ariyoshi Kubota
Hironobu Yasuda
Atsuhiko Zanka
Shunsuke Goto
Satoshi Hirabayashi
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.)
Fujisawa Pharmaceutical Co Ltd
Original Assignee
Fujisawa Pharmaceutical Co Ltd
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 Fujisawa Pharmaceutical Co Ltd filed Critical Fujisawa Pharmaceutical Co Ltd
Publication of WO2001092254A1 publication Critical patent/WO2001092254A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to a method for replacing an organic solvent contained in a clathrate crystal. More specifically, the present invention relates to a method for replacing an organic solvent contained in a clathrate crystal, which comprises replacing the organic solvent contained in the clathrate crystal with water under a humidified atmosphere by using a flow means. About the method. Background art
  • FR1 73657 [3— [N — [(E) -3- (6-acetamidopyridine-1-3_yl) ataliloylglycyl] mono-N-methylamino] -2,6-dichloroben Ndiloxy] _2-Methylquinoline (hereinafter referred to as “FR1 73657”) is a compound having several crystal forms. Of these crystal forms, Form A obtained by crystallization from an acetone-monoaqueous solvent crystals, solid stability good purity also been reported to be high (JP-a 10 3166 77 No.) 0
  • Type A crystal of FR 173657 contains a small amount of acetone used during crystallization. Acetone is harmful to the human body and needs to be removed.However, it is difficult to reduce the acetone content to less than 0.5% specified in the ICH Residual Solvent Guidelines by ordinary vacuum drying. Was.
  • clathrate crystal is a crystal having a clathrate structure (hereinafter referred to as “clathrate crystal”).
  • Force A X-ray crystallography revealed that FR 173657 formed a tunnel structure in this A-type crystal, and that acetone-water was included in the tunnel.
  • a clathrate structure is usually defined as the formation of a tunnel, layer or network when two molecules combine to form a crystal under appropriate conditions. (Tangent lattice) is understood to have a structure in which the other molecule enters the gap.
  • the “clathrate crystal” in the present invention means a crystal having a clathrate structure composed of a usual host and guest.
  • FR 1 7 3 5 7 7 itself serves as a host, and the acetone-water used for crystallization serves as a guest. Since it is included in the clathrate structure of 57, it is considered that it is difficult to be desorbed by methods such as vacuum drying.
  • acetone which is a guest in the clathrate structure
  • a method in which acetone is replaced with water in the presence of water vapor is known. Using this method, it is possible to reduce the content of acetone from the type A crystal of FR1736757 to 0.5% or less.
  • the method of replacing the acetone in the classmate crystals of FR 173 657 with water using a tray dryer is based on the fact that FR 173 657 is hydrophobic. It takes a long time.
  • the type A crystal of FR 1 7 3 6 5 7 has a property that the crystal form tends to change in the presence of excess water, so the method using a shelf type dryer that takes a long time is
  • there is an inconvenience that a different crystal form is mixed in the A-type crystal of FR1736757. Therefore, there has been a demand for the development of a method for efficiently replacing the organic solvent from the A-type crystal of FR1736757 without causing the crystal form transition.
  • the present inventor has surprisingly found that the organic solvent contained in the clathrate crystal can be efficiently replaced with ice by using a flow means under a humidity-controlled atmosphere, and completed the present invention.
  • FIG. 1 shows a vibrating fluidized bed apparatus which is one of the fluidizing means used in the method of the present invention. It is a schematic diagram. BEST MODE FOR CARRYING OUT THE INVENTION
  • the clathrate crystal in the present invention may be a crystal having the above-mentioned clathrate structure.
  • the solvent contained in the clathrate crystal is a solvent used when crystallizing the produced compound. Therefore, the solvent contained in the clathrate crystal includes various forces depending on the compound to be crystallized, such as acetone, acetonitrile, methanol, ethanol, isopropyl alcohol, tetrahydrofuran, and ethyl acetate.
  • examples of the solvent contained in the clathrate structure of FR173657 include acetone and water used to form an A-type crystal of FR173657.
  • the A-type crystal of FR173657 containing acetone as an organic solvent can be produced, for example, according to the method of Example 1 described in JP-A-10-316677.
  • a vibrating fluidized bed apparatus (VD-1 type) manufactured by Chuo Kakoki Co., Ltd. can be used.
  • Fig. 1 shows a schematic diagram of a vibrating fluidized bed apparatus.
  • “under a humidified atmosphere” means that the humidity in the apparatus in which the method of the present invention is performed is adjusted to a predetermined range.
  • the preferable relative humidity under the humidity-controlled atmosphere varies depending on the combination of the clathrate crystal and the organic solvent contained therein. Generally, the higher the humidity, the more the organic solvent in the clathrate crystal is water. Easy to be replaced.
  • the method of the present invention is specifically performed at a relative humidity of 25-90%, more preferably 40-70%.
  • the replacement of the organic solvent contained in the clathrate crystal with water can be confirmed by a conventional method such as a gas chromatography method or a kerfishing method.
  • the time required for this replacement depends on the type of clathrate crystals and the solvent to be replaced, as well as the operating conditions of the apparatus, but usually about 10 to 100 hours is sufficient.
  • reaction mixture was poured into water and extracted with black-mouthed form.
  • the organic layer was washed successively with a saturated aqueous solution of sodium hydrogen carbonate, water and brine, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure.
  • the crystallized solution was filtered, and the crystallized product was washed with methanol (14ral), dried in vacuo at 40 ° C, and subjected to crude anhydrous crystals of FR173657 (6.3 g) (hereinafter referred to as “crude FR173657 crystals”). ").
  • the crystals were crystals containing about 5% methanol.
  • the crystallization liquid was filtered with a centrifuge, and the filtered crystals were washed with methanol (46 L).
  • the obtained crystals were suspended in methanol (805 L), heated to about 65 ° C, cooled, and stirred at 10 to 20 ° C for 1 hour or more.
  • the crystallized solution was filtered, and the filtered crystals were washed with methanol (46 L), dried at 40 ° C under reduced pressure, and dried under a pressure of 8— [3— [N — [(E) -3- (6— Acetamide pyridine-3-yl) acryloylglycine] -N-methylamino]-2,6 _cyclopentabenzizoleoxy]-crude anhydrous crystals of 2-methinolequinoline (FR 173657) (24.6 kg) (hereinafter referred to as " Crude FR173 657 crystal ”).
  • the crystals were crystals containing about 5% methanol.
  • the organic solvent contained in the clathrate crystal can be efficiently replaced with water in a short period of time without accompanying crystal form transition.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pyridine Compounds (AREA)

Abstract

Le problème du remplacement d'un solvant organique contenu dans des cristaux de type clathrate par de l'eau sans provoquer de transition des cristaux est résolu par utilisation de moyens de fluidisation dans une atmosphère conditionnée par l'humidité, les cristaux de type clathrate étant, en particulier, des cristaux de type A de 8-[3-[N-[(E)-3-(6-acetamido-pyridin-3-yl)acryloylglycyl]-N-methylamino]-2,6-dichloro-benzyloxyl[-2-methylquinoline.
PCT/JP2001/004467 2000-05-30 2001-05-28 Procede permettant de remplacer des solvants contenus dans des cristaux de type clathrates Ceased WO2001092254A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2000-160590 2000-05-30
JP2000160590 2000-05-30

Publications (1)

Publication Number Publication Date
WO2001092254A1 true WO2001092254A1 (fr) 2001-12-06

Family

ID=18664756

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2001/004467 Ceased WO2001092254A1 (fr) 2000-05-30 2001-05-28 Procede permettant de remplacer des solvants contenus dans des cristaux de type clathrates

Country Status (1)

Country Link
WO (1) WO2001092254A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0001024A1 (fr) * 1977-08-17 1979-03-07 Roussel-Uclaf Forme cristalline du sel de sodium d'un dérivé oximiné de l'acide 7-amino thiazolyl acétamido céphalosporanique, son procédé de préparation et les compositions pharmaceutiques la renfermant
EP0145395A2 (fr) * 1983-12-02 1985-06-19 Takeda Chemical Industries, Ltd. Cristaux de céphemcarboxylate de sodium
JPH10316677A (ja) * 1997-05-19 1998-12-02 Fujisawa Pharmaceut Co Ltd 結 晶
EP0900582A1 (fr) * 1997-08-21 1999-03-10 Johnson Matthey Public Limited Company Procédé pour enlever des restes de solvants organiques d'une substance crystalline en vrac et utilisation dans l'industrie pharmaceutique
WO2000023439A1 (fr) * 1998-10-21 2000-04-27 Fujisawa Pharmaceutical Co., Ltd. Forme vitreuse d'un antagoniste connu de bradykinine

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0001024A1 (fr) * 1977-08-17 1979-03-07 Roussel-Uclaf Forme cristalline du sel de sodium d'un dérivé oximiné de l'acide 7-amino thiazolyl acétamido céphalosporanique, son procédé de préparation et les compositions pharmaceutiques la renfermant
EP0145395A2 (fr) * 1983-12-02 1985-06-19 Takeda Chemical Industries, Ltd. Cristaux de céphemcarboxylate de sodium
JPH10316677A (ja) * 1997-05-19 1998-12-02 Fujisawa Pharmaceut Co Ltd 結 晶
EP0900582A1 (fr) * 1997-08-21 1999-03-10 Johnson Matthey Public Limited Company Procédé pour enlever des restes de solvants organiques d'une substance crystalline en vrac et utilisation dans l'industrie pharmaceutique
WO2000023439A1 (fr) * 1998-10-21 2000-04-27 Fujisawa Pharmaceutical Co., Ltd. Forme vitreuse d'un antagoniste connu de bradykinine

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