JP6574474B2 - キラルジペプチジルペプチダーゼ−iv阻害剤の製造方法 - Google Patents
キラルジペプチジルペプチダーゼ−iv阻害剤の製造方法 Download PDFInfo
- Publication number
- JP6574474B2 JP6574474B2 JP2017503162A JP2017503162A JP6574474B2 JP 6574474 B2 JP6574474 B2 JP 6574474B2 JP 2017503162 A JP2017503162 A JP 2017503162A JP 2017503162 A JP2017503162 A JP 2017503162A JP 6574474 B2 JP6574474 B2 JP 6574474B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- added
- tfa
- solution
- 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.)
- Active
Links
- 0 C1C2=C*N=C2C*1 Chemical compound C1C2=C*N=C2C*1 0.000 description 8
- RYDSJJXCDQFTKF-INPHSSGZSA-N CC(C)(C)OC(N[C@@H](C1)[C@@H](c(cc(cc2)F)c2F)OCC1O)=O Chemical compound CC(C)(C)OC(N[C@@H](C1)[C@@H](c(cc(cc2)F)c2F)OCC1O)=O RYDSJJXCDQFTKF-INPHSSGZSA-N 0.000 description 1
- RAJQFCVDKPKZMJ-MYIOLCAUSA-N CC1[C@@H](c(cc(cc2)F)c2F)OC=CC1 Chemical compound CC1[C@@H](c(cc(cc2)F)c2F)OC=CC1 RAJQFCVDKPKZMJ-MYIOLCAUSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/30—Oxygen atoms, e.g. delta-lactones
Description
構造式Iaの化合物のBoc基の除去
を含む。
プロパルギルアミン(1.05当量)のTHF(15から20体積)中溶液に、4℃で5分間かけてグリオキサールジメチルアセタール水溶液(1当量)を加えた。得られた溶液を0から2℃で10から15分間エージングした。水素化ホウ素トリアセトキシナトリウムを、添加間で温度を3から15℃に維持しながら、3時間かけて3回に分けて加えた(0.33当量で3回)。得られた混合物を10時間エージングした。冷水を加え、次に10N NaOH溶液(5当量)及びMTBE(10体積)を加えることで反応停止した。得られた二相の層を高撹拌し、静置した。有機層を分離し、NaCl水溶液(5体積で2回)で洗浄し、共沸蒸留してほぼ乾固させることで橙赤色油状物を得て、それを次の段階で直接用いた。
化合物8(1当量)の濃HCl(4から5当量)中溶液を室温で20時間撹拌し、次に減圧下に30から35℃で濃縮して、その体積の半量を除去した。得られた溶液に追加の濃HCl溶液(2当量)を加え、混合物を室温でさらに1日エージングし、MeCN(2体積)で希釈し、50重量%NaOH水溶液を加えることでpHを4に調節した。次に、メシルヒドラジド(1当量)を固体として得て、得られた溶液を室温で終夜エージングした。水(10体積)及びEtOAc(15体積)を加え、次にBoc2O(1当量)及び固体NaHCO3を加えて、pHを6から7とした。ガス発生が停止したら(約5時間)、水層を分離し、有機層を水(2体積)及びブライン(2体積)で洗浄し、濃縮した。次に、粗生成物をカラムクロマトグラフィー(DCM:EtOAc又はHex:EtOAc)によって精製して、生成物10を得た。
ジメチルアセタールアミン8(1当量)のMTBE(10体積)及び水(3体積)中溶液に、Boc−無水物(1.1当量)を0から10℃でゆっくり加えた。反応中、固体NaHCO3を加えることで、pHを調節して6から7とした。室温で5時間エージングした後、有機層を分離し、水(3体積)、ブラインで2回洗浄し、濃縮して粗生成物を得て、それを次の段階で直接用いた。
ジメチルアセタールBoc−保護アミン(化合物3)(1当量)のMeCN:水(20体積)中溶液に、メシルヒドラジド(1.3当量)を加え、次に5重量%FeCl3/SiO2ゲル(0.5当量)を加えた。得られたスラリーを45℃で数日間エージングし、濾過した。濾液を水(5体積)で処理し、EtOAc(15体積)で抽出した。有機層を水(5体積)で2回洗浄し、次に5重量%NaHCO3水溶液及びブラインで洗浄し、共沸脱水して粗混合物を得て、それについてMTBE結晶化を行ってヒドラゾン化合物10を得た。
ヒドラゾン(化合物10(1当量))のMP(10体積)中溶液に、K3PO4(4当量)を室温で加え、得られたスラリーを加熱して45から50℃とし、25時間エージングした。酢酸エチル(20体積)を加え、混合物を水で洗浄し(5体積で2回)、有機層をブラインで洗浄し、Na2SO4で脱水し、濾過し、濃縮して粗生成物を得た。
NiBr2・DME錯体(0.05当量)と、次にCu(I)OAc共触媒(0.05当量)、シクロヘキシルジアミン配位子(0.1当量)及びMeCN(20体積)をフラスコに加えた。得られた混合物を2分間撹拌し、次にヒドラゾン(化合物10(1当量))、K3PO4(1当量)及び酸化剤としての過酢酸tert−ブチル(tBuOOAc、1.1.当量)で処理した。得られたスラリーを25から30℃で15時間エージングし、次にEtOAc(10体積)及び水(5体積)で希釈した。有機層を分離し、5%EDTA−Na2溶液(5体積)、10%クエン酸水溶液、10%NaHCO3水溶液及びブラインで洗浄した。次に、最終有機層を樹脂(原料化合物10に関して100重量%負荷)で処理し、室温で3時間エージングし、濾過し、減圧下に濃縮して粗化合物1を得た。
Claims (7)
- 前記プロセスを一貫プロセスとして行う請求項1に記載の方法。
- 式Iaを結晶化する段階をさらに含む請求項1に記載の方法。
- TFAの量が1から5体積である請求項1に記載の方法。
- TFAの量が3体積である請求項1に記載の方法。
- 前記式Iaの化合物を結晶化させてから、前記Boc保護基を除去する請求項6に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462026763P | 2014-07-21 | 2014-07-21 | |
US62/026,763 | 2014-07-21 | ||
PCT/US2015/040674 WO2016014324A1 (en) | 2014-07-21 | 2015-07-16 | Process for preparing chiral dipeptidyl peptidase-iv inhibitors |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018245751A Division JP6753920B2 (ja) | 2014-07-21 | 2018-12-27 | キラルジペプチジルペプチダーゼ−iv阻害剤の製造方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017523172A JP2017523172A (ja) | 2017-08-17 |
JP6574474B2 true JP6574474B2 (ja) | 2019-09-11 |
Family
ID=55163564
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017503162A Active JP6574474B2 (ja) | 2014-07-21 | 2015-07-16 | キラルジペプチジルペプチダーゼ−iv阻害剤の製造方法 |
JP2018245751A Active JP6753920B2 (ja) | 2014-07-21 | 2018-12-27 | キラルジペプチジルペプチダーゼ−iv阻害剤の製造方法 |
JP2019225001A Active JP6851454B2 (ja) | 2014-07-21 | 2019-12-13 | キラルジペプチジルペプチダーゼ−iv阻害剤の製造方法 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018245751A Active JP6753920B2 (ja) | 2014-07-21 | 2018-12-27 | キラルジペプチジルペプチダーゼ−iv阻害剤の製造方法 |
JP2019225001A Active JP6851454B2 (ja) | 2014-07-21 | 2019-12-13 | キラルジペプチジルペプチダーゼ−iv阻害剤の製造方法 |
Country Status (3)
Country | Link |
---|---|
US (2) | US9862725B2 (ja) |
JP (3) | JP6574474B2 (ja) |
WO (1) | WO2016014324A1 (ja) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107337674B (zh) * | 2016-04-29 | 2019-09-20 | 江苏吉贝尔药业股份有限公司 | 用于dpp-iv抑制剂的四氢吡喃胺衍生物、其药物组合物和制剂以及用途 |
CN107652291B (zh) * | 2016-07-26 | 2020-07-14 | 中国科学院上海药物研究所 | 一种制备手性四氢吡喃衍生物的方法 |
CN106674227B (zh) * | 2016-12-06 | 2019-03-19 | 上海博志研新药物技术有限公司 | 一种奥格列汀及其中间体的制备方法 |
DK3448859T3 (da) | 2017-03-20 | 2019-09-23 | Forma Therapeutics Inc | Pyrrolopyrrolsammensætninger som pyruvatkinase- (pkr) aktivatorer |
CN107459501B (zh) * | 2017-08-22 | 2020-06-09 | 钟桂发 | 一种奥格列汀的手性中间体的制备方法 |
US20230055923A1 (en) | 2018-09-19 | 2023-02-23 | Forma Therapeutics, Inc. | Activating pyruvate kinase r |
MA53668A (fr) | 2018-09-19 | 2021-09-15 | Forma Therapeutics Inc | Traitement de la drépanocytose avec un composé activant la pyruvate kinase r |
CN109053658A (zh) * | 2018-10-08 | 2018-12-21 | 长沙理工大学 | 一种制备奥格列汀关键中间体的新方法 |
Family Cites Families (54)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5041442A (en) | 1990-07-31 | 1991-08-20 | Syntex (U.S.A.) Inc. | Pyrrolo(1,2-a)pyrazines as inhibitors of gastric acid secretion |
DK0688772T3 (da) | 1994-06-16 | 1999-11-01 | Lg Chemical Ltd | Quinolincarboxylsyrederivater med 7-(4-aminomethyl-3-oxim)-pyrrolidinsubstituenter og fremgangsmåde til deres fremstilling |
CN1243707C (zh) | 2000-09-14 | 2006-03-01 | 国家海洋局第一海洋研究所 | 共轭亚油酸的制造方法 |
ATE395912T1 (de) | 2001-03-27 | 2008-06-15 | Merck & Co Inc | Dipeptidylpeptidase-hemmer für die behandlung oder prävention von diabetes |
AU2002310465B2 (en) | 2001-06-20 | 2006-06-15 | Merck & Co., Inc. | Dipeptidyl peptidase inhibitors for the treatment of diabetes |
US7098239B2 (en) | 2001-06-20 | 2006-08-29 | Merck & Co., Inc | Dipeptidyl peptidase inhibitors for the treatment of diabetes |
UA74912C2 (en) | 2001-07-06 | 2006-02-15 | Merck & Co Inc | Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes |
CN1212303C (zh) | 2001-12-31 | 2005-07-27 | 中国科学院新疆理化技术研究所 | 使用混合溶剂合成共轭亚油酸的方法 |
DE60316416T2 (de) | 2002-03-25 | 2008-06-26 | Merck & Co., Inc. | Heterocyclische beta-aminoverbindungen als inhibitoren der dipeptidylpeptidase zur behandlung bzw. prävention von diabetes |
ATE451369T1 (de) | 2002-07-15 | 2009-12-15 | Merck & Co Inc | Piperidinopyrimidindipeptidylpeptidaseinhibitor n zur behandlung von diabetes |
DE60315687T2 (de) | 2002-10-07 | 2008-06-05 | Merck & Co., Inc. | Antidiabetische heterocyclische beta-aminoverbindungen als inhibitoren von dipeptidylpeptidase |
NZ538897A (en) | 2002-10-18 | 2007-02-23 | Merck & Co Inc | Beta-amino heterocyclic dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
MXPA05004890A (es) | 2002-11-07 | 2005-07-22 | Merck & Co Inc | Derivados de fenilalanina como inhibidores de dipeptidilpeptidasa para el tratamiento o prevencion de diabetes. |
CA2508487A1 (en) | 2002-12-04 | 2004-06-17 | Merck & Co., Inc. | Phenylalanine derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
US20060052382A1 (en) | 2002-12-20 | 2006-03-09 | Duffy Joseph L | 3-Amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
CA2512546A1 (en) | 2003-01-17 | 2004-08-05 | Merck & Co., Inc. | 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
WO2004069162A2 (en) | 2003-01-31 | 2004-08-19 | Merck & Co., Inc. | 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
CA2524531A1 (en) | 2003-05-14 | 2004-12-02 | Merck And Co., Inc. | 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
DE602004026440D1 (de) | 2003-06-06 | 2010-05-20 | Merck Sharp & Dohme | Kondensierte indole als dipeptidyl-peptidase-hemmer zur behandlung oder prävention von diabetes |
CA2527806A1 (en) | 2003-06-17 | 2004-12-29 | Merck & Co., Inc. | Cyclohexylglycine derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
JO2625B1 (en) | 2003-06-24 | 2011-11-01 | ميرك شارب اند دوم كوربوريشن | Phosphoric acid salts of dipeptidyl betidase inhibitor 4 |
WO2005011581A2 (en) | 2003-07-31 | 2005-02-10 | Merck & Co., Inc. | Hexahydrodiazepinones as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
AU2004286857A1 (en) | 2003-11-04 | 2005-05-19 | Merck & Co., Inc. | Fused phenylalanine derivatives as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes |
WO2005108382A1 (en) | 2004-05-04 | 2005-11-17 | Merck & Co., Inc. | 1,2,4-oxadiazole derivatives as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
CN1960990A (zh) | 2004-05-18 | 2007-05-09 | 默克公司 | 作为用于治疗或预防糖尿病的二肽基肽酶-ⅳ抑制剂的环己基丙氨酸衍生物 |
CN101014598B (zh) | 2004-06-21 | 2012-06-13 | 默沙东公司 | 作为用于治疗或预防糖尿病的二肽基肽酶-ⅳ抑制剂的氨基环己烷化合物 |
JP2008510810A (ja) | 2004-08-23 | 2008-04-10 | メルク エンド カムパニー インコーポレーテッド | 糖尿病の治療または予防のためのジペプチジルペプチダーゼ−iv阻害剤としての縮合トリアゾール誘導体 |
EP1796669B1 (en) | 2004-10-01 | 2010-09-22 | Merck Sharp & Dohme Corp. | Aminopiperidines as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
WO2006065826A2 (en) | 2004-12-15 | 2006-06-22 | Merck & Co., Inc. | Process to chiral beta amino acid derivatives by asymmetric hydrogenation |
EP1841770B1 (en) | 2005-01-19 | 2009-11-11 | Merck & Co., Inc. | Bicyclic pyrimidines as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
WO2006104997A2 (en) | 2005-03-29 | 2006-10-05 | Merck & Co., Inc. | Tartaric acid salts of a dipeptidyl peptidase-iv inhibitor |
JP2008540426A (ja) | 2005-05-02 | 2008-11-20 | メルク エンド カムパニー インコーポレーテッド | 糖尿病及び肥満の治療のためのジペプチジルペプチダーゼiv阻害薬及びカンナビノイドcb1受容体拮抗薬の組み合わせ |
JP5069678B2 (ja) | 2005-05-25 | 2012-11-07 | メルク・シャープ・エンド・ドーム・コーポレイション | 糖尿病の治療又は予防のためのジペプチジルペプチダーゼiv阻害剤としてのアミノシクロヘキサン |
WO2007035198A2 (en) | 2005-07-25 | 2007-03-29 | Merck & Co., Inc. | Dodecylsulfate salt of a dipeptidyl peptidase-iv inhibitor |
US8017624B2 (en) | 2005-08-26 | 2011-09-13 | Merck Sharp & Dohme Corp. | Fused aminopiperidines as dipeptidyi peptidase-IV inhibitors for the treatment or prevention of diabetes |
AU2006326564B2 (en) | 2005-12-14 | 2011-06-23 | Merck Sharp & Dohme Corp. | Fused aminopiperidines as dipeptidyl peptidase-4 inhibitors for the treatment or prevention of diabetes |
JP5165582B2 (ja) | 2005-12-16 | 2013-03-21 | メルク・シャープ・エンド・ドーム・コーポレイション | ジペプチジルペプチダーゼ−4インヒビターとメトホルミンとを組み合わせた医薬組成物 |
US7750034B2 (en) | 2006-01-25 | 2010-07-06 | Merck Sharp & Dohme Corp. | Aminocyclohexanes as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes |
EP1986652B1 (en) | 2006-02-15 | 2013-03-20 | Merck Sharp & Dohme Corp. | Aminotetrahydropyrans as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
TW200806669A (en) | 2006-03-28 | 2008-02-01 | Merck & Co Inc | Aminotetrahydropyrans as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes |
EP2019677B1 (en) | 2006-05-16 | 2013-08-14 | Merck Sharp & Dohme Corp. | Aminotetrahydropyrans as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
EP2094081B1 (en) | 2006-11-14 | 2012-07-11 | Merck Sharp & Dohme Corp. | Tricyclic heteroaromatic compounds as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
JP2010521859A (ja) * | 2007-03-15 | 2010-06-24 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | 画像を編集するための方法及び装置 |
EP2190428A4 (en) | 2007-08-21 | 2012-02-29 | Merck Sharp & Dohme | HETEROCYCLIC COMPOUNDS AS DIPEPTIDYLPEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES |
JO2870B1 (en) | 2008-11-13 | 2015-03-15 | ميرك شارب اند دوهم كورب | Amino Tetra Hydro Pirans as Inhibitors of Peptide Dipeptide IV for the Treatment or Prevention of Diabetes |
EP2228366B1 (de) | 2009-03-12 | 2011-12-28 | Archimica GmbH | Verfahren zur Herstellung von 2-Amino-4-(halogenalkyl)pyridin-Derivaten durch Cyclisierung geeigneter Nitril-Vorstufen mit Stickstoff-Verbindungen |
US8431564B2 (en) | 2009-07-29 | 2013-04-30 | Merck Sharp & Dohme B.V. | Ring-annulated dihydropyrrolo[2,1-α]isoquinolines |
CN102595897A (zh) | 2009-09-02 | 2012-07-18 | 默沙东公司 | 作为用于糖尿病的治疗或预防的二肽基肽酶-iv抑制剂的氨基四氢吡喃 |
WO2011037793A1 (en) | 2009-09-25 | 2011-03-31 | Merck Sharp & Dohme Corp. | Substituted aminopiperidines as dipeptidyl peptidase-iv inhibitors for the treatment of diabetes |
US8980929B2 (en) | 2010-05-21 | 2015-03-17 | Merck Sharp & Dohme Corp. | Substituted seven-membered heterocyclic compounds as dipeptidyl peptidase-iv inhibitors for the treatment of diabetes |
RU2598072C2 (ru) * | 2011-06-29 | 2016-09-20 | Мерк Шарп И Доум Корп. | Новые кристаллические формы ингибиторов дипептидилпептидазы-iv |
GB201212871D0 (en) * | 2012-07-20 | 2012-09-05 | Eisai Ltd | Novel compounds |
US9156848B2 (en) * | 2012-07-23 | 2015-10-13 | Merck Sharp & Dohme Corp. | Treating diabetes with dipeptidyl peptidase-IV inhibitors |
TWI500613B (zh) * | 2012-10-17 | 2015-09-21 | Cadila Healthcare Ltd | 新穎之雜環化合物 |
-
2015
- 2015-07-16 JP JP2017503162A patent/JP6574474B2/ja active Active
- 2015-07-16 US US15/325,100 patent/US9862725B2/en active Active
- 2015-07-16 WO PCT/US2015/040674 patent/WO2016014324A1/en active Application Filing
-
2017
- 2017-12-05 US US15/831,895 patent/US10053466B2/en active Active
-
2018
- 2018-12-27 JP JP2018245751A patent/JP6753920B2/ja active Active
-
2019
- 2019-12-13 JP JP2019225001A patent/JP6851454B2/ja active Active
Also Published As
Publication number | Publication date |
---|---|
JP6851454B2 (ja) | 2021-03-31 |
US9862725B2 (en) | 2018-01-09 |
JP2017523172A (ja) | 2017-08-17 |
US20170158701A1 (en) | 2017-06-08 |
US20180093992A1 (en) | 2018-04-05 |
JP2020059738A (ja) | 2020-04-16 |
WO2016014324A1 (en) | 2016-01-28 |
US10053466B2 (en) | 2018-08-21 |
JP2019069999A (ja) | 2019-05-09 |
JP6753920B2 (ja) | 2020-09-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6574474B2 (ja) | キラルジペプチジルペプチダーゼ−iv阻害剤の製造方法 | |
DK3233823T3 (en) | PROCEDURES FOR THE PREPARATION OF A DIARYLTHIO HYDANTOIN COMPOUND | |
EP3313841A1 (en) | Process for the preparation of a xanthine-based compound | |
JP6985367B2 (ja) | 新規化合物および方法 | |
US10858353B2 (en) | Intermediates useful for the synthesis of aminopyrimidine derivatives, process for preparing the same, and process for preparing aminopyrimidine derivatives using the same | |
CA2960473A1 (en) | Processes for the preparation of tadalafil and intermediates thereof | |
JPWO2011001976A1 (ja) | スレオ−3−(3,4−ジヒドロキシフェニル)−l−セリンの製造法 | |
KR101623810B1 (ko) | 아세토아세틱 에스테르를 이용한 퓨란, 티오펜, 피롤의 합성방법 | |
JP2009501196A (ja) | 2−メトキシカルボニルメチル−6,6−ジメチル−2−テトラヒドロピラン−カルボン酸の調製方法 | |
JP3831954B2 (ja) | 4−ヒドロキシ−2−ピロリドンの製法 | |
KR20210092768A (ko) | 1-((3s,4r)-4-(2,6-디플루오로-4-메톡시페닐)-2-옥소피롤리딘-3-일)-3-페닐우레아의 제조를 위한 합성 방법 | |
TW201625632A (zh) | Pi3k抑制劑及其鹽之合成 | |
US20150065710A1 (en) | Efficient process for the preparation of lapatinib and salts thereof by means of new intermediates | |
JP5130212B2 (ja) | 光学活性3−アミノ−2,5−ジオキソピロリジン−3−カルボキシレート類およびその製造方法ならびに該化合物の使用 | |
Marchais et al. | A short synthesis of the marine bioactive metabolite (+/−) girolline | |
KR100856133B1 (ko) | 아토르바스타틴의 개선된 제조방법 | |
KR101248123B1 (ko) | 잘레플론의 합성 | |
JP2015522574A (ja) | 2,2−ジフルオロエチルアミンをアルキル化することによる2,2−ジフルオロエチルアミン誘導体の調製方法 | |
EP3971183A1 (en) | Method for producing indole or indazole compound | |
JP2012521993A (ja) | 縮合三環式スルホンアミドの製造プロセス | |
JP2024509995A (ja) | リスジプラムを調製するための方法 | |
KR101325589B1 (ko) | 1-알킬-2-(2-아미노에틸)피롤리딘의 제조방법 | |
KR100929414B1 (ko) | 트로스피움 클로라이드의 제조방법 | |
KR100856891B1 (ko) | 수마트립탄의 제조방법 | |
KR101213467B1 (ko) | 로자탄 대사체 이엑스피-3174 이수화물의 신규한 제조 방법 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180118 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181009 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20181004 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181227 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20190122 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190516 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20190528 |
|
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: 20190723 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190816 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6574474 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
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 |