[go: up one dir, main page]

CN102596908A - 用于制备取代的吲唑和氮杂吲唑化合物的中间体的合成方法 - Google Patents

用于制备取代的吲唑和氮杂吲唑化合物的中间体的合成方法 Download PDF

Info

Publication number
CN102596908A
CN102596908A CN2010800504234A CN201080050423A CN102596908A CN 102596908 A CN102596908 A CN 102596908A CN 2010800504234 A CN2010800504234 A CN 2010800504234A CN 201080050423 A CN201080050423 A CN 201080050423A CN 102596908 A CN102596908 A CN 102596908A
Authority
CN
China
Prior art keywords
formula
metal catalyst
compounds
hydrogen
solvent
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.)
Pending
Application number
CN2010800504234A
Other languages
English (en)
Inventor
H.拉扎维
J.T.里夫斯
S.罗德里古兹
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.)
Boehringer Ingelheim International GmbH
Original Assignee
Boehringer Ingelheim International GmbH
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 Boehringer Ingelheim International GmbH filed Critical Boehringer Ingelheim International GmbH
Publication of CN102596908A publication Critical patent/CN102596908A/zh
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • C07D213/71—Sulfur atoms to which a second hetero atom is attached
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Materials Engineering (AREA)
  • Pain & Pain Management (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Rheumatology (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Catalysts (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Steroid Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

本发明涉及一种制备式I化合物的方法，所述化合物可用于作为制备吲唑和氮杂吲唑取代的化合物的中间体。

Description

用于制备取代的吲唑和氮杂吲唑化合物的中间体的合成方法
相关数据
本申请要求于2009年12月8日提交的美国临时申请61/267,538的优先权。
发明背景
1.技术领域
本发明涉及一种制备式(I)化合物的新方法：
Figure BDA00001613338600011
该化合物用作用于制备吲唑和氮杂吲唑取代的化合物的中间体。
2.背景技术
式II的吲唑和氮杂吲唑取代的化合物已经作为CCR1的抑制剂被公开。此类化合物的实例公开于WO2009/134666和WO2010/036632中。所述化合物用于治疗通过CCR1活性调节或维持的多种疾病和病症，包括自身免疫性疾病，例如类风湿性关节炎及多发性硬化。
Figure BDA00001613338600012
合成这些化合物的关键步骤为形成酰胺键。已经报道了多种方法以实现该目的。例如，按照WO2010/036632中所公开，在此所述的式II化合物可通过将(V)和式(VI)的胺反应而制备，如下图所示：
Figure BDA00001613338600021
上述合成吲唑和氮杂吲唑取代的氨甲酰基化合物的关键中间体为胺中间体VI。所述胺中间体VI的已知合成涉及使下述氰基化合物转化为相应的胺并通过下述2步完成：
1)用硼氢化钠/三氟乙酸/溴化锌进行还原，并原位进行叔丁氧基羰基化反应，
Figure BDA00001613338600022
和
2)利用浓盐酸的异丙醇溶液脱去叔丁氧基羰基的保护
Figure BDA00001613338600023
发明概述
本发明的合成方法相比于已知方法具有以下优点：
1)需要1步而非两步，因此减少了劳动力成本和周期时间；
2)由于无需Boc酸酐、溴化锌、NaBH4或TFA，故降低了成本；
3)由于其将避免在使用NaBH4/TFA时硼烷的形成，故提高了安全性；
4)氢化反应可在工业、商业规模下进行。
因此，本发明的目的在于提供一种制备式(I)的胺中间体化合物的具有上述优点的通用方法。
发明详述
在最广的实施方案中，提供一种制备离子盐形式的式(I)化合物的方法：
Figure BDA00001613338600031
所述方法包括：
i)在0至100℃，优选在25℃，利用金属催化剂，优选基于Pd或Ni的催化剂，更优选钯/炭，最优选含水的10%Pd/C，甚至更优选10%Pd/50%水，使用氢气，优选压力为15-1000psi(优选100至200psi)的氢气，将式(II)化合物氢化2-20小时，优选7小时，过滤除去催化剂，然后用酸溶液或气体，优选用浓盐酸水溶液处理，该反应在选自醇溶剂、酯溶剂、水性酸、醚和甲苯或其它芳香烃溶剂的溶剂(优选甲醇、乙醇、异丙醇或乙酸，更优选甲醇)中进行，得到式(I)化合物：
Figure BDA00001613338600032
其中，R为氢或C1-10烷基，优选为C1-5烷基，更优选为甲基。
本发明的另一实施方案提供一种根据上述实施方案制备式(I)化合物的方法，且其中
式(II)的腈在4位：
Figure BDA00001613338600041
且所得的氨基在式(I)的4位
Figure BDA00001613338600042
除非另有说明，本说明书中所使用的所有术语应理解为本领域技术人员公知的通常含义。
术语“烷基”是指包含1至10个碳原子的饱和脂肪族基团。“烷基”指支链与直链烷基。
本发明的化合物仅为本领域技术人员所了解的被视为“化学稳定”的化合物。
为了使本发明更充分地为人所理解，给出以下实施例。这些实施例的目的在于阐明本发明的优选实施方案，而非意欲以任何方式限制本发明的范围。
合成实施例
Figure BDA00001613338600043
将氢化反应试管加料2-(甲磺酰基)-4-氰基吡啶(8.00g，43.9mmol)、10重量%Pd/C(50%水)(800mg，0.377mmol)和MeOH(48ml)。混合物在25℃、100psi氢气下氢化7小时。将反应混合物过滤以移除该催化剂，用MeOH冲洗，并将滤液浓缩至体积为24ml。添加异丙醇(48ml)，然后添加浓盐酸(4.03ml，48.3mmol，1.1当量)。得到的浆液搅拌18小时、过滤，所得的固体用异丙醇冲洗，真空干燥。获得产物2-(甲磺酰基)吡啶-4-基)甲胺盐酸盐(8.10g，产率82%)，为固体，经HPLC分析不含脱磺酰基杂质，残余的Pd含量为46ppm。

Claims (8)

1.一种制备离子盐形式的式(I)化合物的方法：
Figure FDA00001613338500011
所述方法包括：
i)利用金属催化剂在0-100℃用氢气将式(II)化合物氢化2-20小时，和
ii)滤去催化剂，然后用酸溶液或气体处理，其中该反应在选自下列的溶剂中进行：醇溶剂、酯溶剂、水性酸、醚和甲苯或其他芳香烃溶剂，从而提供式(I)化合物：
Figure FDA00001613338500012
其中R为氢或C1-10烷基。
2.权利要求1的方法，其中：
所述金属催化剂为基于Pd或Ni的催化剂；
所述氢气的压力为15-1000psi；
时间为7小时；
温度为25℃；
所述酸为浓盐酸水溶液；
所述溶剂选自甲醇、乙醇、异丙醇和乙酸；
所述离子盐为盐酸盐。
3.权利要求1或2的方法，其中：
所述金属催化剂为钯/炭；
所述氢气的压力为100-200psi；
所述溶剂为甲醇。
4.权利要求1-3中任一项的方法，其中：
所述金属催化剂为含水的10%钯/炭。
5.权利要求1-4中任一项的方法，其中：
所述金属催化剂为含50%水的10%钯/炭。
6.权利要求1-5中任一项的方法，其中：
式(II)的腈在4位：
Figure FDA00001613338500021
且所得的氨基在式(I)的4位
Figure FDA00001613338500022
7.权利要求1-6中任一项的方法，其中R为C1-5烷基。
8.权利要求1-6中任一项的方法，其中R为甲基。
CN2010800504234A 2009-12-08 2010-12-01 用于制备取代的吲唑和氮杂吲唑化合物的中间体的合成方法 Pending CN102596908A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US26753809P 2009-12-08 2009-12-08
US61/267,538 2009-12-08
PCT/US2010/058594 WO2011071730A1 (en) 2009-12-08 2010-12-01 Process for synthesis of intermediates useful for making substituted indazole and azaindazole compounds

Publications (1)

Publication Number Publication Date
CN102596908A true CN102596908A (zh) 2012-07-18

Family

ID=43416915

Family Applications (1)

Application Number Title Priority Date Filing Date
CN2010800504234A Pending CN102596908A (zh) 2009-12-08 2010-12-01 用于制备取代的吲唑和氮杂吲唑化合物的中间体的合成方法

Country Status (17)

Country Link
US (1) US20110137042A1 (zh)
EP (1) EP2509952A1 (zh)
JP (1) JP2013512954A (zh)
KR (1) KR20120101667A (zh)
CN (1) CN102596908A (zh)
AR (1) AR079324A1 (zh)
AU (1) AU2010328480A1 (zh)
BR (1) BR112012013582A2 (zh)
CA (1) CA2782384A1 (zh)
CL (1) CL2012001300A1 (zh)
EA (1) EA201200820A1 (zh)
IL (1) IL219274A0 (zh)
IN (1) IN2012DN05081A (zh)
MX (1) MX2012006524A (zh)
PH (1) PH12012501153A1 (zh)
TW (1) TW201144282A (zh)
WO (1) WO2011071730A1 (zh)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5216912B2 (ja) 2008-04-29 2013-06-19 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｃｃｒ１受容体拮抗薬としてのインダゾール化合物
CA2722811C (en) * 2008-05-06 2016-07-05 Boehringer Ingelheim International Gmbh Pyrazole compounds as ccr1 antagonists
KR20110060904A (ko) 2008-09-26 2011-06-08 베링거 인겔하임 인터내셔날 게엠베하 Ｃｃｒ1 수용체 길항제로서의 아자인다졸 화합물
DK2491028T3 (da) 2009-10-21 2014-01-13 Boehringer Ingelheim Int Indazol og pyrazolopyridine forbindelser som CCR1 receptor antagonister
EP2493875B1 (en) 2009-10-27 2014-08-06 Boehringer Ingelheim International GmbH Heterocyclic compounds as ccr1 receptor antagonists
EP2563787B1 (en) 2010-04-30 2014-11-26 Boehringer Ingelheim International GmbH Azaindazole amide compounds as ccr1 receptor antagonists
EP2655371B1 (en) 2010-12-23 2015-02-25 Boehringer Ingelheim International GmbH Pyrazolopiperidine compounds as ccr1 receptor antagonists

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1671700A (zh) * 2001-01-12 2005-09-21 安姆根有限公司 取代的烷基胺衍生物和使用方法
CN101141878A (zh) * 2005-03-16 2008-03-12 巴斯福股份公司 联苯-n-（4-吡啶基）甲基磺酰胺
CN101258131A (zh) * 2005-09-01 2008-09-03 伊莱利利公司 作为5－HT<sub>2c</sub>受体激动剂的6－芳烷基氨基－2,3,4,5－四氢－1H－苯并[d]氮杂䓬
CN101410397A (zh) * 2006-03-31 2009-04-15 诺瓦提斯公司 有机化合物
WO2009057827A1 (en) * 2007-10-31 2009-05-07 Nissan Chemical Industries, Ltd. Pyridazinone derivatives and use thereof as p2x7 receptor inhibitors
US20100093724A1 (en) * 2008-09-26 2010-04-15 Boehringer Ingelheim International Gmbh Azaindazole Compounds As CCR1 Receptor Antagonists

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5242931A (en) * 1988-06-09 1993-09-07 Kyowa Hakko Kogyo Co., Ltd. Tricyclic compounds as TXA2 antagonists
CA1338625C (en) * 1988-06-09 1996-10-01 Kyowa Hakko Kogyo Co., Ltd. Tricyclic compounds
US5750542A (en) * 1993-09-28 1998-05-12 Pfizer Benzisoxazole and benzisothizole derivatives as cholinesterase inhibitors
US5612360A (en) * 1992-06-03 1997-03-18 Eli Lilly And Company Angiotensin II antagonists
WO1994001415A1 (fr) * 1992-07-03 1994-01-20 Kumiai Chemical Industry Co., Ltd. Derive heterocyclique condense et desherbant
GB9304919D0 (en) * 1993-03-10 1993-04-28 Celltech Ltd Chemical compounds
BR9405488A (pt) * 1993-06-25 1999-06-01 Kumiai Chemical Industry Co Derivado de indazolsulfoniluréia seu uso e intermediário para sua produção
US6025374A (en) * 1994-12-06 2000-02-15 Merck Sharp & Dohme, Ltd. Azetidine, pyrrolidine and piperidine derivatives as 5HT1 receptor agonists
GB9519563D0 (en) * 1995-09-26 1995-11-29 Merck Sharp & Dohme Therapeutic agents
GB9523583D0 (en) * 1995-11-17 1996-01-17 Merck Sharp & Dohme Therapeutic agents
US5760028A (en) * 1995-12-22 1998-06-02 The Dupont Merck Pharmaceutical Company Integrin receptor antagonists
GB9615449D0 (en) * 1996-07-23 1996-09-04 Merck Sharp & Dohme Therapeutic agents
EA200000385A1 (ru) * 1997-11-04 2000-10-30 Пфайзер Продактс Инк. Терапевтически активные соединения на основе индазольной биоизостерической замены катехина в ингибиторах фосфодиэстеразы типа vi (pde4)
US6331640B1 (en) * 1998-10-13 2001-12-18 Hoffmann-La Roche Inc. Diaminopropionic acid derivatives
ATE303988T1 (de) * 1999-06-14 2005-09-15 Lilly Co Eli Inhibitoren von serin proteasen
AU5895500A (en) * 1999-06-29 2001-01-31 Cor Therapeutics, Inc. Novel indazole peptidomimetics as thrombin receptor antagonists
GB0030303D0 (en) * 2000-12-13 2001-01-24 Lilly Co Eli Compounds
GB0030304D0 (en) * 2000-12-13 2001-01-24 Lilly Co Eli Compounds
GB0030306D0 (en) * 2000-12-13 2001-01-24 Lilly Co Eli Compounds
GB0030305D0 (en) * 2000-12-13 2001-01-24 Lilly Co Eli Compounds
US20050009876A1 (en) * 2000-07-31 2005-01-13 Bhagwat Shripad S. Indazole compounds, compositions thereof and methods of treatment therewith
US7211594B2 (en) * 2000-07-31 2007-05-01 Signal Pharmaceuticals, Llc Indazole compounds and compositions thereof as JNK inhibitors and for the treatment of diseases associated therewith
US7058826B2 (en) * 2000-09-27 2006-06-06 Amphus, Inc. System, architecture, and method for logical server and other network devices in a dynamically configurable multi-server network environment
US20020052373A1 (en) * 2000-10-26 2002-05-02 Zorn Stevin H. Combination treatment for dementia or cognitive deficits associated with alzheimer's disease and parkinson's disease
ES2338539T3 (es) * 2001-11-01 2010-05-10 Icagen, Inc. Pirazolamidas para uso en el tratamiento del dolor.
IL164209A0 (en) * 2002-05-31 2005-12-18 Eisai Co Ltd Pyrazole derivatives and pharmaceutical compositions containing the same
TW200500341A (en) * 2002-11-12 2005-01-01 Astrazeneca Ab Novel compounds
SE0203825D0 (sv) * 2002-12-20 2002-12-20 Astrazeneca Ab Novel fused heterocycles and uses thereof
BRPI0408223A (pt) * 2003-03-12 2006-03-01 Celgene Corp composto, isÈmeros, composição farmacêutica, e, métodos de inibir pde4 e mmp, de modular a produção de tnf-alfa em um mamìfero e de tratar, previnir ou controlar uma doença ou condição
US7129264B2 (en) * 2003-04-16 2006-10-31 Bristol-Myers Squibb Company Biarylmethyl indolines and indoles as antithromboembolic agents
US20040220170A1 (en) * 2003-05-01 2004-11-04 Atkinson Robert N. Pyrazole-amides and sulfonamides as sodium channel modulators
US7371757B2 (en) * 2003-08-15 2008-05-13 Astrazeneca Ab Fused heterocycles as inhibitors of glutamate racemase(MURI)
SE0302487D0 (sv) * 2003-09-18 2003-09-18 Astrazeneca Ab Novel compounds
SE0302486D0 (sv) * 2003-09-18 2003-09-18 Astrazeneca Ab Novel compounds
GB0504828D0 (en) * 2005-03-09 2005-04-13 Merck Sharp & Dohme Therapeutic agents
PT1881823E (pt) * 2005-05-17 2015-03-02 Sarcode Bioscience Inc Composições e métodos para o tratamento de transtornos oculares
WO2007102883A2 (en) * 2005-10-25 2007-09-13 Smithkline Beecham Corporation Chemical compounds
PE20081775A1 (es) * 2006-12-20 2008-12-18 Bristol Myers Squibb Co Compuestos macrociclicos como inhibidores del factor viia
GB0716292D0 (en) * 2007-08-21 2007-09-26 Biofocus Dpi Ltd Imidazopyrazine compounds
JP5216912B2 (ja) 2008-04-29 2013-06-19 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｃｃｒ１受容体拮抗薬としてのインダゾール化合物
CA2722811C (en) * 2008-05-06 2016-07-05 Boehringer Ingelheim International Gmbh Pyrazole compounds as ccr1 antagonists

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1671700A (zh) * 2001-01-12 2005-09-21 安姆根有限公司 取代的烷基胺衍生物和使用方法
CN101141878A (zh) * 2005-03-16 2008-03-12 巴斯福股份公司 联苯-n-（4-吡啶基）甲基磺酰胺
CN101258131A (zh) * 2005-09-01 2008-09-03 伊莱利利公司 作为5－HT<sub>2c</sub>受体激动剂的6－芳烷基氨基－2,3,4,5－四氢－1H－苯并[d]氮杂䓬
CN101410397A (zh) * 2006-03-31 2009-04-15 诺瓦提斯公司 有机化合物
WO2009057827A1 (en) * 2007-10-31 2009-05-07 Nissan Chemical Industries, Ltd. Pyridazinone derivatives and use thereof as p2x7 receptor inhibitors
US20100093724A1 (en) * 2008-09-26 2010-04-15 Boehringer Ingelheim International Gmbh Azaindazole Compounds As CCR1 Receptor Antagonists

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
蔡可迎,等: "吲唑的简便合成", 《化学试剂》, vol. 29, no. 1, 31 January 2007 (2007-01-31), pages 53 - 54 *

Also Published As

Publication number Publication date
AR079324A1 (es) 2012-01-18
EA201200820A1 (ru) 2013-01-30
EP2509952A1 (en) 2012-10-17
MX2012006524A (es) 2012-07-17
WO2011071730A1 (en) 2011-06-16
PH12012501153A1 (en) 2012-10-22
CL2012001300A1 (es) 2012-09-07
US20110137042A1 (en) 2011-06-09
IN2012DN05081A (zh) 2015-10-09
KR20120101667A (ko) 2012-09-14
JP2013512954A (ja) 2013-04-18
AU2010328480A1 (en) 2012-05-17
TW201144282A (en) 2011-12-16
CA2782384A1 (en) 2011-06-16
BR112012013582A2 (pt) 2016-07-05
IL219274A0 (en) 2012-06-28

Similar Documents

Publication Publication Date Title
CN102596908A (zh) 用于制备取代的吲唑和氮杂吲唑化合物的中间体的合成方法
EP2300431B1 (en) Process for the manufacture of an intermediate in the synthesis of dabigatran
CN102285891A (zh) 一种由芳香硝基化合物催化加氢制备芳胺的方法
CN105051031B (zh) 1‑([1,3]二氧戊环‑4‑基甲基)‑1h‑吡唑‑3‑胺的制备方法
CN103865964A (zh) 转氨酶法合成(r)-3-氨基哌啶的方法
WO2016055015A1 (zh) 一种不对称还原法制备西他列汀中间体的方法
CN104059021B (zh) 一种n‑羟基苯胺的制备方法
KR102319577B1 (ko) １-알킬-３-디플루오로메틸-５-플루오르-１ｈ-피라졸-４-카르브알데히드 및 １-알킬-３-디플루오로메틸-５-플루오르-１ｈ-피라졸-４-카르복실레이트의 제조 방법
CN108148044A (zh) 酰胺类化合物及该化合物制备富马酸沃诺拉赞的方法
CN117402083A (zh) 一种亚氨基腙中间体的制备方法
CN110963959B (zh) 一种合成n-保护及非保护的3-羟基-4,4-二甲基哌啶的制备方法
KR20150066777A (ko) 광학활성 인돌린 유도체 및 이의 제조방법
CN101155820B (zh) 6,7,8-三羟基-1-羟甲基-3-氧代-2-氧杂-4-氮杂双环[3.3.1]壬烷的制备方法
EP2961744B1 (en) Intermediates for use in the preparation of indazole derivatives and processes for the preparation thereof
TW200403222A (en) Process for the preparation of amino-pyrrolidine derivatives
JP6182507B2 (ja) ２，３−ジハロゲノアニリンの製造方法
JPH07138210A (ja) アミノプロパン誘導体の製造方法
CN111362824B (zh) 2-(氨甲基)-n,n-二乙基-1-苯基环丙烷甲酰胺及其盐的制备方法
JPH10101646A (ja) アミノメチルピリジン化合物の製造法
CN102766147B (zh) 一种芬司匹利及其氢卤酸盐的制备方法
JP2005170848A (ja) ２，３−ジアミノピリジン類の製造方法
CA2337544C (en) Methods for making optically active 3-aminopyrrolidine-2,5-dione derivative and optically active 3-aminopyrrolidine derivative
WO2020042841A1 (zh) 一种(1r,3s)-3-氨基-1-环戊醇及其盐的制备方法
Cho et al. Ruthenium‐catalyzed formal alkyl group transfer: Synthesis of quinolines from nitroarenes and alkylammonium halides
CN113292477A (zh) 一种铱催化的碳氢活化反应合成异吲哚-1-酮类似物的方法

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C02 Deemed withdrawal of patent application after publication (patent law 2001)
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20120718