JP2008515945A - ヘテロ原子を含む三環式化合物 - Google Patents
ヘテロ原子を含む三環式化合物 Download PDFInfo
- Publication number
- JP2008515945A JP2008515945A JP2007536064A JP2007536064A JP2008515945A JP 2008515945 A JP2008515945 A JP 2008515945A JP 2007536064 A JP2007536064 A JP 2007536064A JP 2007536064 A JP2007536064 A JP 2007536064A JP 2008515945 A JP2008515945 A JP 2008515945A
- Authority
- JP
- Japan
- Prior art keywords
- chlorinating agent
- formula
- organic solvent
- chloro
- epi
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/18—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/01—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing oxygen
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pyridine Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Description
−有機溶媒、例えば上記の有機溶媒、好ましくはエーテルまたは芳香族炭化水素中、N−クロロスクシンイミド、
−塩素化剤として塩素化アルカン、および溶媒として、例えばCCl4(この場合、さらなる有機溶媒は必要ないが、例えば上記のような、さらなる有機溶媒の添加は除外されない。)、
−有機溶媒、例えば上記の有機溶媒、好ましくはエーテルまたは芳香族炭化水素中、C2Cl6のような、有機溶媒中固形塩素化アルカン、
と処理することにより供される。
FR520 アスコマイシン、式ASCの化合物
33−エピ−33−クロロ−FR520 33−エピクロロ−33−デスオキシアスコ マイシン(ピメクロリムス)、式Iの化合物
33−エピ−33−クロロ−FR520
9.69gのs−コリジン(2,4,6−トリメチルピリジン)および15.84gのFR520を、24.8mMolのジクロロトリフェニルホスフィンのトルエン溶液160mlに添加する。得られた混合物を、60℃で1時間撹拌し、H2Oを添加し、得られた2相を分離させ、得られた有機層を飽和NaCl水溶液で洗浄し、乾燥させる。得られた混合物から溶媒を蒸発させ、蒸発により得られた残渣を、シリカゲルのクロマトグラフィーに付す。33−エピ−33−クロロ−FR520が得られる。収率:51.4%。
33−エピ−33−クロロ−FR520
277mgのFR520および138mlのトリフェニルホスフィンのCCl4溶液8mlを、18時間、加熱還流する。得られた混合物にトルエンを添加し、得られた混合物をろ過し、得られたろ液から溶媒を蒸発させる。蒸発後の残渣を、シリカゲルのクロマトグラフィーに付す。33−エピ−33−クロロ−FR520が得られる。収率:45%。
33−エピ−33−クロロ−FR520
100mgのトリフェニルホスフィンのテトラヒドロフラン(THF)溶液1mlを、THF1.2ml中、50mgのN−クロロスクシンイミドに滴下する。得られた混合物を、室温で0.5時間撹拌し、0.1mlのピリジンを添加し、次いでTHF2ml中、244mgのFR520を添加し、得られた混合物を65℃で1時間撹拌する。混合物を、トルエンで希釈し、水を添加し、得られた2相を分離させる。得られた有機相を1N HCl、H2Oおよび飽和NaCl溶液で洗浄し、乾燥させる。得られた溶液から、溶媒を蒸発させ、蒸発により得られた残渣を、シリカゲルのクロマトグラフィーに付す。33−エピ−33−クロロ−FR520が得られる。収率:48.1%。
33−エピ−33−クロロ−FR520の結晶化
実施例1から3の何れかに記載の方法により得られた27gの粗33−エピ−33−クロロ−FR520を、180mlのエタノール中に溶解し、65mlの水を添加する。得られた混合物を4℃に維持し、さらに水を添加し、得られた混合物を4℃でさらに4時間維持する。23.5gの結晶化した33−エピ−33−クロロ−FR520が、純度98%で得られる。
Claims (10)
- 保護基を回避する、請求項1に記載の方法。
- 有機溶媒中、所望により塩基の存在下で、式ASCの化合物(アスコマイシン)と適当な塩素化剤を反応させる工程、およびその反応混合物から得られた式Iの化合物を単離する工程を含む、請求項1から3のいずれか一項に記載の方法。
- 前記塩素化剤が、ジクロロトリフェニルホスホランである、請求項4に記載の方法。
- 有機溶媒中、塩基の存在下で、FR520(アスコマイシン)と塩素化剤(ここで、塩素化剤は、有機溶媒中、トリフェニルホスフィンをN−クロロスクシンイミドで処理することにより供される。)を反応させる工程を含む、請求項1から5のいずれか一項に記載の方法。
- 前記有機溶媒が、芳香族炭化水素、エーテルおよびニトリルからなる群から選択される、請求項6に記載の方法。
- 前記塩基がピリジンである、請求項4から7のいずれか一項に記載の方法。
- 有機溶媒中、式ASCの化合物と塩素化剤(ここで、塩素化剤は、トリフェニルホスフィンを塩素化アルカンで処理することにより供される。)を反応させる工程を含む、請求項1から5のいずれか一項に記載の方法。
- 塩素化アルカンがCCl4である、請求項9に記載の方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0422643A GB0422643D0 (en) | 2004-10-12 | 2004-10-12 | Organic compounds |
GB0422643.7 | 2004-10-12 | ||
GB0427599A GB0427599D0 (en) | 2004-12-16 | 2004-12-16 | Organic compounds |
GB0427599.6 | 2004-12-16 | ||
PCT/EP2005/010889 WO2006040111A2 (en) | 2004-10-12 | 2005-10-10 | Heteroatoms-containing tricyclic compounds |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008515945A true JP2008515945A (ja) | 2008-05-15 |
JP5032326B2 JP5032326B2 (ja) | 2012-09-26 |
Family
ID=36084355
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007536064A Active JP5032326B2 (ja) | 2004-10-12 | 2005-10-10 | ヘテロ原子を含む三環式化合物 |
Country Status (28)
Country | Link |
---|---|
US (1) | US7514554B2 (ja) |
EP (1) | EP1802635B8 (ja) |
JP (1) | JP5032326B2 (ja) |
KR (1) | KR101228188B1 (ja) |
CN (1) | CN101031573B (ja) |
AR (1) | AR051386A1 (ja) |
AU (1) | AU2005293799B2 (ja) |
BR (1) | BRPI0516873A (ja) |
CA (1) | CA2581046C (ja) |
DK (1) | DK1802635T3 (ja) |
EC (1) | ECSP077384A (ja) |
ES (1) | ES2389206T3 (ja) |
GT (1) | GT200500282A (ja) |
HK (1) | HK1105634A1 (ja) |
IL (1) | IL182307A (ja) |
JO (1) | JO2727B1 (ja) |
MA (1) | MA28932B1 (ja) |
MX (1) | MX2007004258A (ja) |
MY (1) | MY140880A (ja) |
NO (1) | NO338603B1 (ja) |
NZ (1) | NZ554010A (ja) |
PE (1) | PE20060581A1 (ja) |
PL (1) | PL1802635T3 (ja) |
PT (1) | PT1802635E (ja) |
RU (1) | RU2394037C2 (ja) |
TN (1) | TNSN07133A1 (ja) |
TW (1) | TWI361192B (ja) |
WO (1) | WO2006040111A2 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006060614A1 (en) * | 2004-12-01 | 2006-06-08 | Teva Gyógyszergyár Zàrtköruen Muködo Rèszvènytàrsasàg | Methods for preparing pimecrolimus |
IT1394309B1 (it) | 2009-05-22 | 2012-06-06 | Poli Ind Chimica Spa | Nuovo approccio chimico-enzimatico alla sintesi del pimecrolimus |
CN106854228B (zh) * | 2015-12-08 | 2020-05-29 | 博瑞生物医药(苏州)股份有限公司 | 一种吡美莫司的制备方法 |
EP3178824A1 (en) | 2015-12-08 | 2017-06-14 | Medichem, S.A. | Process for preparing pimecrolimus |
US10975097B2 (en) * | 2017-05-01 | 2021-04-13 | Meda Ab | Process to convert technical ascomycin into purified pimecrolimus |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03223291A (ja) * | 1989-11-09 | 1991-10-02 | Sandoz Ag | 異原子含有三環化合物 |
US5352671A (en) * | 1989-11-09 | 1994-10-04 | Sandoz Ltd. | Heteroatoms-containing tricyclic compounds |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4464366A (en) * | 1979-12-19 | 1984-08-07 | Ciba Geigy Corporation | Cephem compounds having a terminal aminocarboxylic acid grouping and containing an azacyclyl(thio)ureido group |
US4894366A (en) * | 1984-12-03 | 1990-01-16 | Fujisawa Pharmaceutical Company, Ltd. | Tricyclo compounds, a process for their production and a pharmaceutical composition containing the same |
EP0480623A1 (en) | 1990-10-11 | 1992-04-15 | Merck & Co. Inc. | New halomacrolides and derivatives having immunosuppressive activity |
MY110603A (en) | 1993-05-27 | 1998-08-29 | Novartis Ag | Tetrahydropyran derivatives |
US6160117A (en) * | 1997-11-06 | 2000-12-12 | Zeneca Limited | Chemical process |
GB0012383D0 (en) * | 2000-05-22 | 2000-07-12 | Novartis Ag | Organic compounds |
US6667312B2 (en) * | 2000-12-08 | 2003-12-23 | 3M Innovative Properties Company | Thioether substituted imidazoquinolines |
-
2005
- 2005-10-07 GT GT200500282A patent/GT200500282A/es unknown
- 2005-10-09 JO JO2005138A patent/JO2727B1/en active
- 2005-10-10 DK DK05793907.6T patent/DK1802635T3/da active
- 2005-10-10 JP JP2007536064A patent/JP5032326B2/ja active Active
- 2005-10-10 NZ NZ554010A patent/NZ554010A/en unknown
- 2005-10-10 CA CA2581046A patent/CA2581046C/en active Active
- 2005-10-10 US US11/575,757 patent/US7514554B2/en active Active
- 2005-10-10 WO PCT/EP2005/010889 patent/WO2006040111A2/en active Application Filing
- 2005-10-10 AU AU2005293799A patent/AU2005293799B2/en active Active
- 2005-10-10 BR BRPI0516873-2A patent/BRPI0516873A/pt not_active Application Discontinuation
- 2005-10-10 ES ES05793907T patent/ES2389206T3/es active Active
- 2005-10-10 KR KR1020077008216A patent/KR101228188B1/ko active IP Right Grant
- 2005-10-10 PT PT05793907T patent/PT1802635E/pt unknown
- 2005-10-10 MX MX2007004258A patent/MX2007004258A/es active IP Right Grant
- 2005-10-10 PL PL05793907T patent/PL1802635T3/pl unknown
- 2005-10-10 RU RU2007117497/04A patent/RU2394037C2/ru active
- 2005-10-10 CN CN2005800333070A patent/CN101031573B/zh active Active
- 2005-10-10 EP EP05793907.6A patent/EP1802635B8/en active Active
- 2005-10-11 AR ARP050104257A patent/AR051386A1/es not_active Application Discontinuation
- 2005-10-11 MY MYPI20054764A patent/MY140880A/en unknown
- 2005-10-11 PE PE2005001202A patent/PE20060581A1/es not_active Application Discontinuation
- 2005-10-11 TW TW094135403A patent/TWI361192B/zh active
-
2007
- 2007-03-29 IL IL182307A patent/IL182307A/en active IP Right Grant
- 2007-04-11 TN TNP2007000133A patent/TNSN07133A1/fr unknown
- 2007-04-11 EC EC2007007384A patent/ECSP077384A/es unknown
- 2007-04-12 MA MA29826A patent/MA28932B1/fr unknown
- 2007-04-24 NO NO20072127A patent/NO338603B1/no unknown
- 2007-10-05 HK HK07110850.1A patent/HK1105634A1/xx unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03223291A (ja) * | 1989-11-09 | 1991-10-02 | Sandoz Ag | 異原子含有三環化合物 |
US5352671A (en) * | 1989-11-09 | 1994-10-04 | Sandoz Ltd. | Heteroatoms-containing tricyclic compounds |
CA2029694C (en) * | 1989-11-09 | 2001-05-08 | Karl Baumann | Heteroatoms-containing tricyclic compounds |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102637844B1 (ko) | 키나아제를 조절하는 1h-피롤로[2,3b]피리딘 유도체의 합성 | |
TWI683810B (zh) | 用於製備二芳基硫乙內醯脲化合物之方法 | |
JP6800334B2 (ja) | Btk阻害剤を調製するプロセス | |
JP5032326B2 (ja) | ヘテロ原子を含む三環式化合物 | |
WO2018136001A1 (en) | Process for preparing apalutamide | |
JP3173602B2 (ja) | エンイン誘導体の新規製造中間体及びその製造法 | |
JP7144873B2 (ja) | スガマデクスナトリウム塩の製造方法 | |
TW202233569A (zh) | 製備3—氟—5—(((1S,2aR)—1,3,3,4,4—五氟—2a—羥基—2,2a,3,4—四氫—1H—環戊[cd]茚—7—基)氧基)苯甲腈之方法 | |
WO2021116979A1 (en) | Process for the preparation of lasmiditan and of a synthesis intermediate | |
JP2007230963A (ja) | 2,4−ジ置換ピリジンの製造法 | |
JPWO2019131695A1 (ja) | 1−[5−(2−フルオロフェニル)−1−(ピリジン−3−イルスルホニル)−1h−ピロ−ル−3−イル]−n−メチルメタンアミンモノフマル酸塩の製造法 | |
JP6375374B2 (ja) | ピリミジン中間体の製造方法 | |
JP2004525927A (ja) | ランソプラゾール及びその中間体の製造方法 | |
JPH01313474A (ja) | 5‐クロル‐3‐クロルスルホニル‐2‐チオフエンカルボン酸エステルの製造方法 | |
JP7023177B2 (ja) | 9-(2-置換フェニル)-9h-カルバゾールの製造方法 | |
JP3355797B2 (ja) | α位に塩素原子を有するピリジン類の製造方法 | |
JPH0244835B2 (ja) | ||
JP2008137899A (ja) | 4−メチルチオ−3−ブテニルイソチオシアナートの製造方法 | |
JPWO2018105492A1 (ja) | 3−(ピリジル−2−アミノ)プロピオニトリル及びその類縁体の製造方法 | |
JP2017525725A (ja) | 3−フェニル/ヘテロアリール−6−フェノキシ−8−アルキルアミノ−イミダゾ[1,2−b]ピリダジン誘導体を調製する方法 | |
JP2003221394A (ja) | キヌクリジン誘導体の製造方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20081009 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120207 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120507 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120511 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120514 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120612 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120628 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5032326 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150706 Year of fee payment: 3 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150706 Year of fee payment: 3 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |