TW201144282A - Process for synthesis of intermediates useful for making substituted indazole and azaindazole compounds - Google Patents
Process for synthesis of intermediates useful for making substituted indazole and azaindazole compounds Download PDFInfo
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- TW201144282A TW201144282A TW099142648A TW99142648A TW201144282A TW 201144282 A TW201144282 A TW 201144282A TW 099142648 A TW099142648 A TW 099142648A TW 99142648 A TW99142648 A TW 99142648A TW 201144282 A TW201144282 A TW 201144282A
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- 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
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- 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
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- 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]
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- 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
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- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pain & Pain Management (AREA)
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- Materials Engineering (AREA)
- Rheumatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
201144282 六、發明說明: 【發明所屬之技術領域】 本發明係關於一種製備式(I)化合物之新穎的方法:
/、、0 其作係用於製備經取代吲唑及氮雜吲唑化合物之中間物。 本申請案主張於2009年12月8曰申請之美國臨時申請案 第61/267,538號之權益。 【先前技術】 式II之經取代吲唑及氮雜吲唑化合物已描述為CCR1之抑 制劑。該等化合物之實例揭示於WO 2009/1 34666及WO 2010/036632中。該等化合物係用於治療經由CCR1活性調 節或維持之各種疾病及失調症,包括自身免疫疾病,例如 類風濕性關節炎及多發性硬化。
Ο R. R
II(X=C 或 N) 合成此等化合物之關鍵步驟係形成醯胺鍵。已揭示若干 方法以完成此。例如,參考文獻WO 2010/036632中所揭 示,其中所描述之式II化合物可藉由使(V)及式(VI)胺反應 151427.doc 201144282 而製備’如下圖所示:
V VI 上述合成經取代吲唑及氮雜吲唑化合物之中間物實質上 係胺中間物V卜已知的中間物VI之合成包括使下述氰基化 合物轉化為對應的胺並通過2個步驟方法完成,該2個步驟 方法包括1)減少硼氫化鈉/三氟乙酸/溴化鋅並原位進行丁 氧基幾基化作用,
NHPG 、'0 —s'丨 R 々ο 气 1 · NaBH4 2. t護基 of。 及2)利用含於異丙醇之濃鹽酸脫去叔丁氧基羰基之保護。 NHPG Η 酸 nh2 °1"° 〇t〇 【發明内容】 本發明之合成方法較之已知方法具有以下優點: 1) 需要1個步驟而非兩個步驟,因此減少勞動力成本及週 期時間; 2) 由於無需Boe gf、》臭化鋅、仏卵4、或tfa減少成 151427.doc 201144282 本; 3) 由於其可在使用Na BH4/TFA時避免㈣形成之可能性, 故提高安全性; 4) 可於工業、商業規模下使用氫化作用。 t本發月之目的係、提供—種製備式⑴之胺中間物具有 上述優點之常規方法。 【實施方式】 於最廣泛通用之實施例中,提供_種製備離子鹽形式之 式(I)化合物之方法: nh2
其包括: i)於0至loot,較佳25。(:下,利用金屬觸媒,較佳以以或 Νι為主之觸媒,更佳鈀覆碳,最佳含水之1〇% ,尤佳 10% Pd/50。/。水之觸媒,以氫氣,較佳壓力為15至1〇〇〇 (較佳100至200psi)之氫氣,歷時2至2〇小時,最佳7小時, 將式(II)化合物氫化,並濾去該觸媒,然後以酸溶液或氣 體,較佳以濃鹽酸水溶液處理,該反應係在選自醇溶劑、 酯溶劑、酸之水溶液、醚及甲苯或其他芳香烴溶劑之溶劑 (較佳為曱醇、乙醇、異丙醇或乙酸,更佳為甲醇)中進 行’以提供式(I)化合物: 151427.doc 201144282
觸媒/¾
其中R係氫或C1-10烷基,較佳為C1_5烷基,更佳為甲基β 於本發明之另一實施例中提供一種根據上述實施例製備 式⑴化合物之方法,且其中 式(Π)之腈係在4之位置:
(II), 且所得之胺基係在式(I)之4位置 ΝΗ.
本說明書中所使用之所有術語(除另外說明之外)應理解 為相關技術中所知之其等的普通含義β 術語「院基」係指包含丨至10個碳原子之飽和脂肪族基 團。「烧基」同時指支鏈或無支鏈烷基。 本發明之該等化合物僅係熟習此項技術者所瞭解之視為 「化學穩定」之彼等。 闡述以下實例以使此發明得以更充分為人理解。此等實 151427.doc •6- 201144282 例係出於闡明此發明較佳實施例之目的,而並非意欲以任 何方式限制本發明範圍。 合成實例
以 2-(曱基橫 gf 基)-4·氰基°比〇定(8.00 g,43.9 mmol)、1〇 重量 % Pd/C(50%水)(800 mg,0.377 mmol)及 MeOH(48 ml) 注滿一氫化管。於25°C 100 psi氫氣下歷時7小時使該混合 物氫化。過濾該反應混合物以移除該觸媒,用Me〇H沖洗 並濃縮該濾液至體積為24 m卜添加異丙醇(48 ml),然後 濃鹽酸(4.03 ml,48.3 mmlo ’ 1.1 eq)。攪拌所得漿歷時18 小時,過濾’並以異丙醇沖洗所得固體並於真空下乾燥。 獲得呈固體(8.10 g,產率82%)之產物2-(甲基磺醯基)吡啶_ 4-基)曱胺鹽酸鹽,其經HPLC分析不含脫磺醯基雜質,且 具有46 ppm殘餘Pd含量。 151427.doc
Claims (1)
- 201144282 七、申請專利範圍: 1· 一種製備離子鹽形式之式(I)化合物之方法:其包括: i) 利用金屬觸媒於0至100°C下以氫氣使式(II)化合物氫化 2至20小時,及 ii) 濾去該觸媒然後以酸性溶液或氣體處理,其中該反應 係在選自醇溶劑、酯溶劑、酸之水溶液、醚及甲醇或其 他芳香烴溶劑之溶劑中進行,以提供式(I)化合物:其中R係氫或C1-10烷基。 2.如請求項1之方法,其中: 該金屬觸媒係以Pd或Ni為主之觸媒; 該氫氣係在15至lOOOpsi之壓力下; 時間為7小時; 溫度為25°C ; 該酸係濃鹽酸水溶液; 151427.doc 201144282 該溶劑係選自甲醇、乙醇、異丙醇及乙酸; 該離子鹽係氫氣化物。 3. 如請求項1或2之方法,其中: 該金屬觸媒為鈀覆碳; 該氫氣係在1〇〇至200psi之壓力下; 該溶劑係曱醇。 4. 如請求項1或2之方法,其中: 該金屬觸媒為10%鈀覆碳,其含水; 5. 如請求項1或2之方法,其中: 該金屬觸媒10%鈀覆碳,其含5〇%水; 6. 如請求項1或2之方法,其中: 式(Π)之腈係在4之位置:且所得之胺基係在式(I)之4位置7. 如請求項1或2之方法,其中尺係^乃烷基。 8. 如睛求項1或2之方法,其中r係甲基。 151427.doc 201144282 四、指定代表圖: (一) 本案指定代表圖為:(無) (二) 本代表圖之元件符號簡單說明: 五、本案若有化學式時,請揭示最能顯示發明特徵的化學式:(I) 151427.doc
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US26753809P | 2009-12-08 | 2009-12-08 |
Publications (1)
Publication Number | Publication Date |
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TW201144282A true TW201144282A (en) | 2011-12-16 |
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Application Number | Title | Priority Date | Filing Date |
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TW099142648A TW201144282A (en) | 2009-12-08 | 2010-12-07 | Process for synthesis of intermediates useful for making substituted indazole and azaindazole compounds |
Country Status (16)
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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) |
TW (1) | TW201144282A (zh) |
WO (1) | WO2011071730A1 (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2722923C (en) | 2008-04-29 | 2016-08-02 | Boehringer Ingelheim International Gmbh | Indazole compounds as ccr1 receptor antagonists |
US8293917B2 (en) * | 2008-05-06 | 2012-10-23 | Boehringer Ingelheim International Gmbh | Pyrazole compounds as CCR1 antagonists |
CN102227425A (zh) | 2008-09-26 | 2011-10-26 | 贝林格尔·英格海姆国际有限公司 | 作为ccr1受体拮抗剂的氮杂吲唑化合物 |
EP2491028B1 (en) | 2009-10-21 | 2013-12-11 | Boehringer Ingelheim International GmbH | Indazole and pyrazolopyridine compounds as ccr1 receptor antagonists |
JP5542214B2 (ja) | 2009-10-27 | 2014-07-09 | 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受容体アンタゴニストとしての複素環化合物 |
JP5793182B2 (ja) | 2010-04-30 | 2015-10-14 | 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受容体アンタゴニストとしてのアザインダゾールアミド化合物 |
WO2012087782A1 (en) | 2010-12-23 | 2012-06-28 | Boehringer Ingelheim International Gmbh | Pyrazolopiperidine compounds as ccr1 receptor antagonists |
Family Cites Families (47)
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 |
BR9305569A (pt) * | 1992-07-03 | 1995-12-26 | Kumiai Chemical Industry Co | Derivados heterocíclicos condensados e herbicidas |
GB9304919D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
EP0657450B1 (en) * | 1993-06-25 | 1998-09-09 | KumaiI Chemical Industry Co., Ltd. | Indazolesulfonylurea derivative, use thereof, and intermediate for production thereof |
AU699281B2 (en) * | 1994-12-06 | 1998-11-26 | Merck Sharp & Dohme Limited | 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 |
WO2000076971A2 (en) * | 1999-06-14 | 2000-12-21 | Eli Lilly And Company | Serine protease inhibitors |
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 |
GB0030305D0 (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 |
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 |
US20050009876A1 (en) * | 2000-07-31 | 2005-01-13 | Bhagwat Shripad S. | Indazole compounds, compositions thereof and methods of treatment 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 |
US6995162B2 (en) * | 2001-01-12 | 2006-02-07 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
ES2338539T3 (es) * | 2001-11-01 | 2010-05-10 | Icagen, Inc. | Pirazolamidas para uso en el tratamiento del dolor. |
US7429609B2 (en) * | 2002-05-31 | 2008-09-30 | Eisai R & D Management Co., Ltd. | Pyrazole compound and medicinal composition 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 |
NZ542671A (en) * | 2003-03-12 | 2008-12-24 | Celgene Corp | 7-Amido-isoindolyl compounds and their pharmaceutical uses |
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 |
WO2005016929A1 (en) * | 2003-08-15 | 2005-02-24 | Astrazeneca Ab | Fused heterocylcles 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 |
CA2599555A1 (en) * | 2005-03-16 | 2006-09-21 | Basf Aktiengesellschaft | Biphenyl-n-(4-pyridyl) methylsufonamides |
SI2444079T1 (sl) * | 2005-05-17 | 2017-05-31 | Sarcode Bioscience Inc. | Sestavki in postopki za zdravljenje očesnih motenj |
BRPI0615048A2 (pt) * | 2005-09-01 | 2010-03-30 | Lilly Co Eli | composto, composição farmacêutica, e, uso de um composto |
EP1940394A4 (en) * | 2005-10-25 | 2009-07-08 | Smithkline Beecham Corp | CHEMICAL COMPOUNDS |
BRPI0710110A2 (pt) * | 2006-03-31 | 2011-08-02 | Novartis Ag | compostos orgánicos |
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 |
WO2009057827A1 (en) * | 2007-10-31 | 2009-05-07 | Nissan Chemical Industries, Ltd. | Pyridazinone derivatives and use thereof as p2x7 receptor inhibitors |
CA2722923C (en) * | 2008-04-29 | 2016-08-02 | Boehringer Ingelheim International Gmbh | Indazole compounds as ccr1 receptor antagonists |
US8293917B2 (en) * | 2008-05-06 | 2012-10-23 | Boehringer Ingelheim International Gmbh | Pyrazole compounds as CCR1 antagonists |
CN102227425A (zh) | 2008-09-26 | 2011-10-26 | 贝林格尔·英格海姆国际有限公司 | 作为ccr1受体拮抗剂的氮杂吲唑化合物 |
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2010
- 2010-12-01 US US12/957,483 patent/US20110137042A1/en not_active Abandoned
- 2010-12-01 BR BR112012013582A patent/BR112012013582A2/pt not_active IP Right Cessation
- 2010-12-01 CN CN2010800504234A patent/CN102596908A/zh active Pending
- 2010-12-01 WO PCT/US2010/058594 patent/WO2011071730A1/en active Application Filing
- 2010-12-01 JP JP2012543154A patent/JP2013512954A/ja active Pending
- 2010-12-01 KR KR1020127014239A patent/KR20120101667A/ko not_active Application Discontinuation
- 2010-12-01 AU AU2010328480A patent/AU2010328480A1/en not_active Abandoned
- 2010-12-01 EP EP10787651A patent/EP2509952A1/en not_active Withdrawn
- 2010-12-01 CA CA2782384A patent/CA2782384A1/en not_active Abandoned
- 2010-12-01 MX MX2012006524A patent/MX2012006524A/es not_active Application Discontinuation
- 2010-12-01 EA EA201200820A patent/EA201200820A1/ru unknown
- 2010-12-01 IN IN5081DEN2012 patent/IN2012DN05081A/en unknown
- 2010-12-07 AR ARP100104528A patent/AR079324A1/es unknown
- 2010-12-07 TW TW099142648A patent/TW201144282A/zh unknown
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2012
- 2012-04-19 IL IL219274A patent/IL219274A0/en unknown
- 2012-05-18 CL CL2012001300A patent/CL2012001300A1/es unknown
Also Published As
Publication number | Publication date |
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JP2013512954A (ja) | 2013-04-18 |
AU2010328480A1 (en) | 2012-05-17 |
MX2012006524A (es) | 2012-07-17 |
BR112012013582A2 (pt) | 2016-07-05 |
AR079324A1 (es) | 2012-01-18 |
IN2012DN05081A (zh) | 2015-10-09 |
CA2782384A1 (en) | 2011-06-16 |
CN102596908A (zh) | 2012-07-18 |
EP2509952A1 (en) | 2012-10-17 |
WO2011071730A1 (en) | 2011-06-16 |
EA201200820A1 (ru) | 2013-01-30 |
KR20120101667A (ko) | 2012-09-14 |
US20110137042A1 (en) | 2011-06-09 |
IL219274A0 (en) | 2012-06-28 |
CL2012001300A1 (es) | 2012-09-07 |
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