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SK284596B6 - Spôsob výroby (1S,4R)- alebo (1R,4S)-4-(2-amino-6-chlór-9-H- purin-9-yl)-2-cyklopentén-1-metanolu alebo jeho solí - Google Patents

Spôsob výroby (1S,4R)- alebo (1R,4S)-4-(2-amino-6-chlór-9-H- purin-9-yl)-2-cyklopentén-1-metanolu alebo jeho solí Download PDF

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SK284596B6
SK284596B6 SK403-2004A SK4032004A SK284596B6 SK 284596 B6 SK284596 B6 SK 284596B6 SK 4032004 A SK4032004 A SK 4032004A SK 284596 B6 SK284596 B6 SK 284596B6
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amino
methanol
cyclopentene
chloro
salts
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Walter Brieden
Josef Schr�Er
Christine Bernegger-Egli
Eva Maria Urban
Michael Petersen
Jean-Paul Roduit
Katja Berchtold
Holger Breitbach
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Lonza Ag
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Abstract

Opisuje sa spôsob výroby (1S,4S)- alebo (1R,4S)-4-(2-amino- 6-chlór-9-H-purin-9-yl)-2-cyklopentén-1-metanolu, alebo jeho solí, vzorcov (I), (II), podľa ktorého sa (1R,4S)- alebo (1S,4R)-1-amino-4-(hydroxymetyl)-2-cyklopenténhydrogén-D-, alebo L-vínan premení pomocou N-(2-amino-4,6-dichlórpyrimidin)-5-yl)- formamidu na (1S,4R)- alebo (1R,4S)-4-[2-amino-6-chlór-5- formamido-4-pyrimidinyl)-amino]-2-cyklopentén-1-metanol a ten sa cyklizuje na konečný produkt.ŕ

Description

Oblasť techniky
Predkladaný vynález sa týka nového spôsobu výroby (1S,4R)- alebo (lR,4S)-4-(2-amino-6-chlór-9-H-purin-9-yl)-2-cyklopentén-l-metanolu alebo jeho solí vzorcov (I) a (H).
Naproti tomu je známe, že nesubstituovaný (±)-2-azabicyklo[2.2.l]hept-5-en-3-ón vzorca (III)
Doterajší stav techniky (1 R,4S)-1 -Amino-4-(hydroxymetyl)-2-cyklopentén je dôležitým medziproduktom pri výrobe karbocyklických nukleozidov ako napr. CarbovirR (Campbell et al., J. Org. Chem. 1995,60,4602-4616).
Spôsob výroby (lR,4S)-l-amino-4-(hydroxymetyl)-2-cyklopenténu sa opisuje napríklad v Campbell et. al (ibid) a Park K. H. a Rapoport H. (J. Org. Chem. 1994, 59, 394-399).
Tento postup využíva buď D-glukón-ó-laktón alebo D-serín ako východiskovú látku, pričom je potrebné cca 15 syntetických krokov vedúcich k (lR,4S)-N-terc-butoxykar-bonyl-4-hydroxymetyl-2-cyklopenténu, ktorý je v ďalšom odchránením premenený na (lR,4S)-l-amino-4-(hydroxymetyl)-2-cyklopentén.
Obidva tieto postupy sú nákladné, zdĺhavé a v prevádzkovom meradle nevhodné. Patent WO 93/17020 opisuje spôsob výroby (lR,4S)-l-amino-4-(hydroxymetyl)-2-cyklopenténu tak, že (lR,4S)-4-amino-2-cyklopentén-l-karboxylová kyselina sa redukuje lítiumalumíniumhydridom na požadovaný produkt.
Nevýhodou tohto spôsobu výroby je po prvé skutočnosť, že dochádza zároveň k redukcii dvojitej väzby cyklopenténového kruhu. Zložitá je i samotná manipulácia s lítiumalumíniumhydridom a navyše je tento spôsob veľmi nákladný.
Taylor S. J. et al. (Tetrahedron: Asymmetry Vol. 4, No. 6, 1993, 117-1128) opisujú spôsob výroby (1R,4S)-1-amino-4-(hydroxymetyl)-2-cyklopenténu vychádzajúci z (±)-2-azabicyklo[2.2.1]hept-5-en-3-ónu. Táto východisková látka sa najprv pomocou mikroorganizmov druhu Pseudomonas solanacearum alebo Pseudomonas fluores-cences premení na (lR,4S)-2-azabicyklo[2.2.1]hept-5-en-3-ón, ktorý sa ďalej premení pomocou di-terc-butyldikarbonátu na (1 R,4S)-N-terc-butoxykarbonyl-2-aza-bicyklo-[2.2.1 ]hept-5-en-3-ón a následne redukuje nátriumborohydridom s kyselinou trifluóroctovou na požadovaný produkt.
I tento postup je však veľmi nákladný.
Ďalej opisujú Martinéz et al. (J. Org. Chem. 1996, 61, 7963-7966) desaťstupňovú syntézu (lR,4S)-l-amino-4-(hydroxymetyl)-2-cyklopenténu vychádzajúc z dietylesteru dialkylmalónovej kyseliny. Tento spôsob výroby je ale taktiež zdĺhavý a v prevádzkovom meradle nevhodný.
Ďalej je známe, že N-substituované (±)-2-azabicyklo[2.2.1]hept-5-en-3-óny, ktoré nesú elektronegatívne substituenty, sa môžu redukovať hydridom kovu na zodpovedajúce N-substituované aminoalkoholy (Katagiri et al., Tetrahedron Letters, 1989, 30, 1645-1648; Taylor et al., ibid).
sa redukuje lítiumalumíniumhydridom na (±)-2-azabicyklo[2.2.1]oktén (Malpass and Tweedle, J. Chem. Soc, Perkin Trans 1, 1977, 874-884) a že priama redukcia (±)-2-azabicyklo[2.2.2]hept-5-en-3-ónu na zodpovedajúci aminoalkohol sa do tohto času považovala za neuskutočniteľnú (Katagiri et al., ibid+ Taylor et al., ibid).
Taktiež sa opisuje štiepenie racemického l-amino-4-(hydroxymetyl)-2-cyklopenténu pomocou kyseliny (-)-dibenzoylvínnej (US-A 5 034 394). Nevýhodou tejto reakcie je, že kyselina (-)-dibenzoylvínna je drahá a delenie sa musí uskutočňovať za prítomnosti presne definovanej zmesi acetonitrilu a etanolu. Túto zmes rozpúšťadiel nie je možné deliť a musí sa preto spaľovať.
Úlohou predkladaného vynálezu bolo poskytnúť jednoduchý, ekonomický a nenákladný spôsob výroby (1S,4R)alebo (1 R,4S)-4-(2-amino-6-chlór-9-H-purin-9-yl)-2-cyklopentén-1-metanolu alebo jeho solí.
Podstata vynálezu
Podľa tohto vynálezu sa výroba (IS,4R)- alebo (1 R,4S)-4-(2-amino-6-chlór-9-H-purin-9-yl)-2-cyklopentén-1-metanolu alebo jeho soli, vzorcov (I), (II)
uskutočňuje tak, že sa premení (1R,4S)- alebo (1S,4R)-1-amino-4-(hydroxymetyl)-2-cyklopenténhydrogén-D- alebo L-vínan pomocou N-(2-amino-4,6-dichlórpyrimidin)-5-yl)-formamidu vzorca (IV)
(IV) na (1 S,4R)- alebo (lR,4S)-4-[(2-amino-6-chlór-5-formamido-4-pyrimidinyl)-amino] -2-cyklopentén-1 -metanol vzorcov (V), (VI)
M
(VI) a potom sa známym spôsobom cyklizuje na zlúčeniny vzorcov (I) a (II).
N-(2-Amino-4,6-dichlórpyrimidín)-5-yl)formamid je možné vyrobiť podľa WO 95/21 161.
Účelne sa táto reakcia uskutočňuje v prítomnosti zásady. Na tento účel sú vhodné rovnaké zásady ako v prípade už opísaných zásad používaných na uvoľnenie (1R,4S)- alebo (lS,4R)-l-amino-4-(hydroxymetyl)-2-cyklopenténu zo zodpovedajúceho vínanu.
Účelne sa táto reakcia uskutočňuje v protickom rozpúšťadle. Ako protické rozpúšťadlo sa môžu použiť C!.6-alkoholy ako metanol, etanol, propanol, izopropanol, butanol alebo izobutanol. Potom sa (1S,4R)- alebo (lR,4S)-4-[(2-amino-6-chlór-5-formamido-4-pyrimidinyl)-amino]-2-cyklopentén-1-metanol vzorca (V) alebo (VI) cyklizuje známym spôsobom podľa WO 95/21 161 na konečný produkt vzorca (I) alebo (II).
Zvyčajne sa cyklizácia uskutočňuje v roztoku s trialkylortoformiátmi v prítomnosti koncentrovanej vodnej kyseliny. Ako trialkylortoformiáty je možné použiť napríklad trimetyl- alebo trietylortoformiát.
Ako vodnú kyselinu je možné použiť kyselinu chlorovodíkovú, kyselinu sírovú alebo kyselinu metánsulfónovú.
(IV) na (1S,4R)- alebo (lR,4S)-4-[(2-amino-6-chlór-5-formamido-4-pyrimidmyl)-amino]-2-cyklopentén-1 -metanol vzorcov (V), (VI)
a nakoniec sa cyklizuje na zlúčeniny vzorcov (I) alebo (II).
Príklady uskutočnenia vynálezu
Príklad 1
Výroba [4(R)-(2-amino-6-chlórpurín-9-yl)cyklopent-2-én-l(S)-yl]metanolu z lR,4S-(4-amino-2-cyklopenten-l-yl)-metanol-D-hydrogenvínanu
47,4 g lR,4S-(4-Amino-2-cyklopenten-l-yl)metanol-D-hydrogenvínanu (0,18 molov, ee > 98 %) sa rozpustilo v 200 ml etanolu. Pri laboratórnej teplote sa pridalo 54,6 g NaHCO3 (0,65 molov) a 37,3 g (0,18 molov) N-(2-amino-4,6-dichlór-4-pyrimidyl)-formamidu. Zmes sa refluxovala počas 9 hodín a potom sa ochladila na laboratórnu teplotu. Soli sa odfiltrovali a ďalej premyli 50 ml etanolu. Filtrát sa skoncentroval na 280 g na rotačnej odparke. Do takto získaného roztoku sa zaviedlo 18,4 g plynného HCI pri teplote < 25 °C. Potom sa pridalo 95,5 g (0,9 molov) trimetylortoformiátu a zmes sa zahriala na teplotu 40 °C (10 minút). Pri tejto teplote sa zmes naočkovala chlórpurín hydrochloridom. Po 2 hodinách pri teplote 42 °C vykryštalizoval produkt. Suspenzia sa ochladila na teplotu 15 °C. Produkt sa filtroval a 3-krát premyl 50 ml etanolu a napokon sa produkt vákuovo vysušil pri teplote 50 °C. Výťažok bol 41,9 g (75,8 %). Béžový prášok, obsah (HPLC): 95,0 %.

Claims (1)

  1. PATENTOVÉ NÁROKY
    1. Spôsob výroby (1S,4R)- alebo (lR,4S)-4-(2-amino-6-chlór-9-H-purin-9-yl)-2-cyklopentén-1 -metanolu, alebo jeho solí, vzorcov (I), (II) vyznačujúci sa tým, že sa (1R,4S)- alebo (1 S,4R)-1 -amino-4-(hydroxymetyl)-2-cyklopenténhydrogén-D- alebo L-vínan premení pomocou N-(2-amino-4,6-dichlórpyrimidin)-5-yl)-formamidu vzorca (IV)
SK403-2004A 1997-11-27 1998-11-23 Spôsob výroby (1S,4R)- alebo (1R,4S)-4-(2-amino-6-chlór-9-H- purin-9-yl)-2-cyklopentén-1-metanolu alebo jeho solí SK284596B6 (sk)

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CH273997 1997-11-27
CH278197 1997-12-03
CH13398 1998-01-21
CH72398 1998-03-27
EP98118895 1998-10-07

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SK403-2004A SK284596B6 (sk) 1997-11-27 1998-11-23 Spôsob výroby (1S,4R)- alebo (1R,4S)-4-(2-amino-6-chlór-9-H- purin-9-yl)-2-cyklopentén-1-metanolu alebo jeho solí
SK401-2004A SK284594B6 (sk) 1997-11-27 1998-11-23 Spôsob výroby derivátov aminoalkoholov a ich soli
SK402-2004A SK284595B6 (sk) 1997-11-27 1998-11-23 Spôsob výroby (1S,4R)-4-(2-amino-6-chlór-9H-purín-9-yl)-2- cyklopentén-1-metanolu alebo jeho solí
SK1615-98A SK284416B6 (sk) 1997-11-27 1998-11-23 Spôsob výroby derivátov aminoalkoholov

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SK401-2004A SK284594B6 (sk) 1997-11-27 1998-11-23 Spôsob výroby derivátov aminoalkoholov a ich soli
SK402-2004A SK284595B6 (sk) 1997-11-27 1998-11-23 Spôsob výroby (1S,4R)-4-(2-amino-6-chlór-9H-purín-9-yl)-2- cyklopentén-1-metanolu alebo jeho solí
SK1615-98A SK284416B6 (sk) 1997-11-27 1998-11-23 Spôsob výroby derivátov aminoalkoholov

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Families Citing this family (20)

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ES2211216T3 (es) 1998-12-23 2004-07-01 Lonza Ag Procedimiento para la preparacion de derivados de 1-amino-4-(hidroximetil)-ciclopent-2-eno opticamente activo.
US8042740B2 (en) * 2000-11-24 2011-10-25 Metrologic Instruments, Inc. Method of reading bar code symbols on objects at a point-of-sale station by passing said objects through a complex of stationary coplanar illumination and imaging planes projected into a 3D imaging volume
DK1434870T3 (da) * 2001-09-25 2007-04-30 Hoffmann La Roche Enzymatisk fremgangsmåde til fremstilling af substitueret 2-amino-3-(2-amino-phenylsulfanyl)-propionsyre
KR100684772B1 (ko) 2004-12-08 2007-02-22 주식회사농심 찹쌀을 이용한 푸딩 촉감의 식품 및 그의 제조 방법.
US8805134B1 (en) 2012-02-17 2014-08-12 Soraa Laser Diode, Inc. Methods and apparatus for photonic integration in non-polar and semi-polar oriented wave-guided optical devices
US9250044B1 (en) 2009-05-29 2016-02-02 Soraa Laser Diode, Inc. Gallium and nitrogen containing laser diode dazzling devices and methods of use
US9039655B2 (en) 2009-11-06 2015-05-26 Crisi Medical Systems, Inc. Medication injection site and data collection system
CN102603652A (zh) * 2011-12-27 2012-07-25 河南师范大学 5-甲酰基嘧啶碳环核苷及制备方法
CN102719512B (zh) * 2012-06-21 2014-06-11 浙江工业大学 一种r-2-（4-羟基苯氧基）丙酸酯的制备方法
CN104098478B (zh) * 2013-04-08 2017-05-17 安徽贝克联合制药有限公司 一种氨基醇的拆分方法
WO2016067182A2 (en) * 2014-10-27 2016-05-06 Granules India Limited Process for the preparation of amino alcohol derivatives or salts thereof
CN104974051A (zh) * 2015-06-30 2015-10-14 苏州开元民生科技股份有限公司 (1S,4R)-cis-4-氨基-2-环戊烯-1-甲醇盐酸盐的合成方法
CN106220515A (zh) * 2016-08-12 2016-12-14 郸城巨鑫生物科技有限公司 一种(1r,4s)‑1‑氨基‑4‑羟甲基‑2‑环戊烯盐酸盐的合成方法
JP2019532959A (ja) * 2016-10-06 2019-11-14 ヤンセン ファーマシューティカ エヌ．ベー． Ｂｔｋ阻害剤を調製するための方法および中間体
US11421843B2 (en) 2018-12-21 2022-08-23 Kyocera Sld Laser, Inc. Fiber-delivered laser-induced dynamic light system
US11239637B2 (en) 2018-12-21 2022-02-01 Kyocera Sld Laser, Inc. Fiber delivered laser induced white light system
CN109735582B (zh) * 2018-12-24 2022-06-21 浙江工业大学 一种脂肪酶催化在线合成环己醇类β-氨基醇衍生物的方法
US12000552B2 (en) 2019-01-18 2024-06-04 Kyocera Sld Laser, Inc. Laser-based fiber-coupled white light system for a vehicle
US11884202B2 (en) 2019-01-18 2024-01-30 Kyocera Sld Laser, Inc. Laser-based fiber-coupled white light system
CN116730856B (zh) * 2023-06-19 2024-06-07 浙江竹子制药有限公司 一种氨甲环酸的合成方法

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2534533A (en) 1945-11-05 1950-12-19 Hermann I Schlesinger Methods of preparing alkali metal borohydrides
DE947702C (de) 1954-07-16 1956-08-23 Metallgesellschaft Ag Verfahren zur Herstellung borhaltiger Metallhydride
US4268672A (en) * 1977-02-09 1981-05-19 The Regents Of The University Of Minnesota Adenosine deaminase resistant antiviral purine nucleosides and method of preparation
US4138562A (en) 1977-02-09 1979-02-06 The Regents Of The University Of Minnesota Adenosine deaminase resistant antiviral purine nucleosides and method of preparation
US4916224A (en) * 1988-01-20 1990-04-10 Regents Of The University Of Minnesota Dideoxycarbocyclic nucleosides
GB8815265D0 (en) * 1988-06-27 1988-08-03 Wellcome Found Therapeutic nucleosides
AU626314B2 (en) * 1988-09-09 1992-07-30 Ferag Ag Method and means for tabloid further processing
MY104575A (en) * 1989-12-22 1994-04-30 The Wellcome Foundation Ltd Therapeutic nucleosides.
JPH0484896A (ja) * 1990-07-26 1992-03-18 Kyowa Hakko Kogyo Co Ltd 光学活性なイソインドリン―１―オン誘導体の製造法
US5200527A (en) 1991-04-08 1993-04-06 Lonza Ltd. Process for the production of 2-azabicyclo [2.2.1] hept-5-en-3-one
FR2676042B1 (fr) 1991-05-02 1993-07-23 Commissariat Energie Atomique Procede de preparation d'un borohydrure de metal alcalin tel que le borohydrure de lithium.
GB9204015D0 (en) 1992-02-25 1992-04-08 Wellcome Found Therapeutic nucleosides
GB9402161D0 (en) * 1994-02-04 1994-03-30 Wellcome Found Chloropyrimidine intermediates
GB9417249D0 (en) * 1994-08-26 1994-10-19 Wellcome Found A novel salt
JPH09124564A (ja) * 1995-11-06 1997-05-13 Nikko Rika Kk 光学活性体混合物ならびにその製造方法
DE69608121T2 (de) * 1995-11-16 2000-09-28 G.D. Searle & Co., Chicago N-geschützte/n-substituierte beta-aminohydroxysulfonate
DE59712095D1 (de) * 1996-05-30 2004-12-30 Lonza Ag Visp Verfahren zur herstellung von aminoalkoholen und derivaten davon
SK284810B6 (sk) * 1997-05-13 2005-12-01 Lonza Ag Spôsob výroby (1S,4R)- alebo (1R,4S)-4-(2-amino-6-chlór-9-H- purín-9-yl)-2-cyklopentén-1-metanolu
GB9721780D0 (en) * 1997-10-14 1997-12-10 Glaxo Group Ltd Process for the synthesis of chloropurine intermediates

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