JP2015521635A5 - - Google Patents

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JP2015521635A5
JP2015521635A5 JP2015518855A JP2015518855A JP2015521635A5 JP 2015521635 A5 JP2015521635 A5 JP 2015521635A5 JP 2015518855 A JP2015518855 A JP 2015518855A JP 2015518855 A JP2015518855 A JP 2015518855A JP 2015521635 A5 JP2015521635 A5 JP 2015521635A5
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Prior art keywords
solifenacin
compound
formula
salt
impurity
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Pending
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JP2015518855A
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Japanese (ja)
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JP2015521635A (en
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Priority claimed from PCT/EP2012/002769 external-priority patent/WO2014005601A1/en
Publication of JP2015521635A publication Critical patent/JP2015521635A/en
Publication of JP2015521635A5 publication Critical patent/JP2015521635A5/ja
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Claims (15)

式Ｉ
Figure 2015521635
の化合物の調製方法であって、
ａ）式ＩＩ
Figure 2015521635
の化合物を、 式ＩＩＩ
Figure 2015521635
（上式中、Ｒは次のもの：
Figure 2015521635
の一つを表し、Ｒ’は次のもの：
Figure 2015521635
の一つを表す）の化合物と反応させて、式Ａの化合物
Figure 2015521635
（上式中、Ｒは上の定義の通りである）
を生成せしめる工程；
ｂ）インサイツで得られてもよい式Ａの化合物を式ＩＶ
Figure 2015521635
の化合物で処理する工程；
ｃ）任意選択的にソリフェナシン遊離塩基を分離する工程；及び
ｄ）任意選択的にソリフェナシン遊離塩基をソリフェナシン塩に転換させる工程
を含む方法。 Formula I
Figure 2015521635
A method for preparing a compound of
a) Formula II
Figure 2015521635
A compound of formula III
Figure 2015521635
(Where R is the following:
Figure 2015521635
R ′ represents one of the following:
Figure 2015521635
By a of representing one) compounds reacting a compound of formula A
Figure 2015521635
(In the above formulas, R Ru as Der defined above)
The step of generating
b) A compound of formula A which may be obtained in situ is represented by formula IV
Figure 2015521635
Treating with a compound of:
c) optionally separating solifenacin free base; and d) optionally converting solifenacin free base to a solifenacin salt. 式ＩＩの化合物と式ＩＩＩの化合物との反応が、極性非プロトン性溶媒又は非極性溶媒、例えばアセトニトリル、ジクロロメタン、トルエン、ジメチルホルムアミド、テトラヒドロフラン又はそれらの混合物から選択される適切な溶媒中で行われる、請求項１に記載の方法。 The reaction of the compound of formula II with the compound of formula III is carried out in a suitable solvent selected from polar aprotic solvents or nonpolar solvents such as acetonitrile, dichloromethane, toluene, dimethylformamide, tetrahydrofuran or mixtures thereof. The method of claim 1. 式ＩＶの化合物での式Ａの化合物の処理が、極性非プロトン性溶媒又は非極性溶媒、例えばアセトニトリル、ジクロロメタン、トルエン、酢酸エチル、ジメチルホルムアミド、テトラヒドロフラン又はそれらの混合物から選択される溶媒中で行われる、請求項１に記載の方法。 Treatment of the compound of formula A with the compound of formula IV is carried out in a solvent selected from polar aprotic solvents or nonpolar solvents such as acetonitrile, dichloromethane, toluene, ethyl acetate, dimethylformamide, tetrahydrofuran or mixtures thereof. The method of claim 1, wherein the method is performed. ソリフェナシン塩を得るために使用される酸が、塩酸及び臭化水素酸等の無機酸又はコハク酸、シュウ酸及び酒石酸等の有機酸から選択される、請求項１に記載の方法。   The process according to claim 1, wherein the acid used to obtain the solifenacin salt is selected from inorganic acids such as hydrochloric acid and hydrobromic acid or organic acids such as succinic acid, oxalic acid and tartaric acid. Ｒが上に記載の通りの意味を有する、請求項１に記載の通り得られた式Ａ
Figure 2015521635
の化合物。 R have the meanings as described above, wherein A, obtained as described in claim 1
Figure 2015521635
Compound. ソリフェナシン又はその塩の調製のための式Ａの化合物の使用。Use of a compound of formula A for the preparation of solifenacin or a salt thereof. ＨＰＬＣにより測定して０．１面積％未満の量で１−（｛［（１Ｓ）−１−フェニル−３，４−ジヒドロイソキノリン−２（１Ｈ）−イル］カルボニル｝オキシ）ピロリジン−２，５−ジオン（不純物Ｘ）を含むソリフェナシン又はその塩。   1-({[(1S) -1-phenyl-3,4-dihydroisoquinolin-2 (1H) -yl] carbonyl} oxy) pyrrolidine-2,5 in an amount of less than 0.1 area% as measured by HPLC -Solifenacin or a salt thereof containing dione (impurity X). ＨＰＬＣにより測定して０．１面積％未満の量でビス［（１Ｓ）−１−フェニル−１，２，３，４−テトラヒドロイソキノリン−２−イル−］メタノン（不純物Ｙ）を含むソリフェナシン又はその塩。   Solifenacin containing bis [(1S) -1-phenyl-1,2,3,4-tetrahydroisoquinolin-2-yl-] methanone (impurity Y) in an amount of less than 0.1 area% as measured by HPLC or its salt. ＨＰＬＣにより測定して０．１面積％未満の量で（１’Ｓ，３Ｒ）−３−［［（１’−フェニル−１’，２’，３’，４’−テトラヒドロ−２’−イソキノリル）カルボニル］オキシ］キヌクリジン１−オキシド（不純物Ｚ）を含むソリフェナシン又はその塩。   (1 ′S, 3R) -3-[[(1′-phenyl-1 ′, 2 ′, 3 ′, 4′-tetrahydro-2′-isoquinolyl) in an amount of less than 0.1 area% as determined by HPLC ) Carbonyl] oxy] quinuclidine 1-oxide (impurity Z), solifenacin or a salt thereof. ＨＰＬＣにより測定して、それぞれ約０．２面積％未満の量で、不純物Ｘ、不純物Ｙ又は不純物Ｚの少なくとも一つを含む、９９％を越える純度を有する、ソリフェナシン又はその塩。   Solifenacin or a salt thereof having a purity of greater than 99%, comprising at least one of impurity X, impurity Y or impurity Z, each in an amount of less than about 0.2 area% as measured by HPLC. ＨＰＬＣにより測定して約９９％から約９９．９９％の総純度を有する、請求項８から１１に記載のソリフェナシン又はその塩。   12. Solifenacin or a salt thereof according to claims 8 to 11 having a total purity of about 99% to about 99.99% as measured by HPLC. 分離された不純物１−（｛［（１Ｓ）−１−フェニル−３，４−ジヒドロイソキノリン−２（１Ｈ）−イル］カルボニル｝オキシ）ピロリジン−２，５−ジオン。
Figure 2015521635
Isolated impurity 1-({[(1S) -1-phenyl-3,4-dihydroisoquinolin-2 (1H) -yl] carbonyl} oxy) pyrrolidine-2,5-dione.
Figure 2015521635
 分離された不純物ビス［（１Ｓ）−１−フェニル−１，２，３，４−テトラヒドロイソキノリン−２−イル］メタノン。
Figure 2015521635
Isolated impurity bis [(1S) -1-phenyl-1,2,3,4-tetrahydroisoquinolin-2-yl] methanone.
Figure 2015521635
 不純物Ｘ、不純物Ｙ及び不純物Ｚを実質的に含まないソリフェナシン又はその塩と一又は複数の薬学的に許容される賦形剤とを含有する薬学的組成物。   A pharmaceutical composition comprising solifenacin or a salt thereof substantially free of impurities X, Y and Z and one or more pharmaceutically acceptable excipients. ここに開示された方法によって調製されるソリフェナシン又はその塩と一又は複数の薬学的に許容される賦形剤とを含有する薬学的組成物。   A pharmaceutical composition comprising solifenacin or a salt thereof prepared by the method disclosed herein and one or more pharmaceutically acceptable excipients.
JP2015518855A 2012-07-02 2012-07-02 Method for preparing solifenacin or a salt thereof Pending JP2015521635A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2012/002769 WO2014005601A1 (en) 2012-07-02 2012-07-02 A process for the preparation of solifenacin or a salt thereof

Publications (2)

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JP2015521635A JP2015521635A (en) 2015-07-30
JP2015521635A5 true JP2015521635A5 (en) 2015-09-10

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EP (1) EP2867210A1 (en)
JP (1) JP2015521635A (en)
CN (1) CN104411687A (en)
WO (1) WO2014005601A1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104133011A (en) * 2014-07-01 2014-11-05 北京万全德众医药生物技术有限公司 Method for separating and analyzing solifenacin succinate intermediate and correlated substances
CN105348278B (en) * 2014-11-14 2017-11-17 天津市医药集团技术发展有限公司 A kind of preparation method of butanedioic acid Solifenacin impurity
CN105566315B (en) * 2016-01-20 2017-07-18 成都华宇制药有限公司 A kind of post processing of Solifenacin and the method for preparing butanedioic acid Solifenacin

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NO2005012I1 (en) * 1994-12-28 2005-06-06 Debio Rech Pharma Sa Triptorelin and pharmaceutically acceptable salts thereof
AUPP405098A0 (en) * 1998-06-12 1998-07-02 Access Pharmaceuticals Australia Pty Limited Novel methods of preparation of vitamin b12 derivatives suitable for conjugation to pharmaceuticals
UA85567C2 (en) * 2003-12-23 2009-02-10 Тиботек Фармасьютикелз Лтд. Process for the preparation of (3r,3as,6ar)-hexahydrofuro [2,3-b] furan-3-yl (1s,2r)-3-[[(4-aminophenyl) sulfonyl] (isobutyl) amino]-1-benzyl-2-hydroxypropylcarbamate
JPWO2005087231A1 (en) * 2004-03-16 2008-01-24 アステラス製薬株式会社 Solifenacin-containing composition
ZA200608614B (en) * 2004-03-25 2008-06-25 Astellas Pharma Inc Composition for solid pharmaceutical preparation of solifenacin or salt thereof
CA2630846A1 (en) 2005-12-21 2007-07-05 Teva Pharmaceutical Industries Ltd. Intermediates for preparing solifenacin
CZ300699B6 (en) * 2006-06-21 2009-07-22 Zentiva, A. S. Process for preparing solifenacin
AR066206A1 (en) * 2007-03-30 2009-08-05 Medichem Sa PROCESS FOR SYNTHESIS OF SOLIFENACINE
ITMI20080195A1 (en) * 2008-02-08 2009-08-09 Dipharma Francis Srl PROCEDURE FOR THE PREPARATION OF SOLIFENACIN
ES2753979T3 (en) * 2009-03-09 2020-04-15 Megafine Pharma P Ltd A new method for the preparation of solifenacin and a new intermediate for it

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