HRP20130099T1 - POSTUPAK PRIPREME [(1R), 2S]-2-AMINOPROPIONSKA KISELINA-2-[4-(4-FLUORO-2-METIL-1H-INDOL-5-ILOKSI)-5-METILPIROLO]2,1-f-[1,2,4-TRIAZIN-6-ILOKSI]-1-METILETIL ESTERA - Google Patents
POSTUPAK PRIPREME [(1R), 2S]-2-AMINOPROPIONSKA KISELINA-2-[4-(4-FLUORO-2-METIL-1H-INDOL-5-ILOKSI)-5-METILPIROLO]2,1-f-[1,2,4-TRIAZIN-6-ILOKSI]-1-METILETIL ESTERA Download PDFInfo
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- HRP20130099T1 HRP20130099T1 HRP20130099TT HRP20130099T HRP20130099T1 HR P20130099 T1 HRP20130099 T1 HR P20130099T1 HR P20130099T T HRP20130099T T HR P20130099TT HR P20130099 T HRP20130099 T HR P20130099T HR P20130099 T1 HRP20130099 T1 HR P20130099T1
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- Prior art keywords
- compound
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- process according
- reaction
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Links
- 238000000034 method Methods 0.000 title claims 17
- 238000002360 preparation method Methods 0.000 title claims 3
- 150000001875 compounds Chemical class 0.000 claims 28
- 238000006243 chemical reaction Methods 0.000 claims 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 6
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 2
- 229940126062 Compound A Drugs 0.000 claims 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 2
- GOOHAUXETOMSMM-GSVOUGTGSA-N R-propylene oxide Chemical compound C[C@@H]1CO1 GOOHAUXETOMSMM-GSVOUGTGSA-N 0.000 claims 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 239000003638 chemical reducing agent Substances 0.000 claims 2
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 claims 2
- 239000007822 coupling agent Substances 0.000 claims 2
- TYRGLVWXHJRKMT-QMMMGPOBSA-N n-benzyloxycarbonyl-l-serine-betalactone Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-QMMMGPOBSA-N 0.000 claims 2
- 230000003647 oxidation Effects 0.000 claims 2
- 238000007254 oxidation reaction Methods 0.000 claims 2
- 239000000376 reactant Substances 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 claims 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical group Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims 1
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 238000005660 chlorination reaction Methods 0.000 claims 1
- 238000001816 cooling Methods 0.000 claims 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims 1
- 229940098779 methanesulfonic acid Drugs 0.000 claims 1
- 239000012022 methylating agents Substances 0.000 claims 1
- 238000010791 quenching Methods 0.000 claims 1
- 230000000171 quenching effect Effects 0.000 claims 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Claims (16)
1. Postupak pripreme Spoja I formule
[image]
koji obuhvaća korake
a) reakcije Spoja A formule
[image]
Spoj A
sa sredstvom za metiliranje u odgovarajućem otapalu radi dobivanja Spoja B formule
[image]
Spoj B
b) koji reagira u kontinuiranoj oksidaciji nakon čega slijedi reakcija gašenja radi pripreme Spoja C formule
[image]
Spoj C
i zaštita da se Spoj C prevede u Spoj D formule
[image]
Spoj D
c) kloriranje Spoja D radi dobivanja Spoja E formule
[image]
Spoj E
d) koji se veže sa Spojem F formule
[image]
Spoj F
da se dobije Spoj G formule, koji po izboru može kristalizirati radi poboljšanja kvalitete, i
[image]
Spoj G
e) s kojeg se zatim uklanja zaštita i reagira s (R)-(+)-propilen oksidom u odgovarajućem otapalu, i po izboru se rekristalizira radi poboljšanja kvalitete, a da se dobije Spoj H formule
[image]
Spoj H
f) koji reagira s Cbz-L-alaninom i sredstvom za spajanje radi dobivanja Spoja J formule
[image]
Spoj J
g) s kojeg se uklanja zaštita i rekristalizira se da se dobije kristalni Spoj I.
2. Postupak kontinuirane reakcije za pripremu Spoja C formule
[image]
Spoj C
iz Spoja B formule
[image]
Spoj B
koji obuhvaća oksidaciju Spoja B u kontinuiranom reaktoru kroz koji u doticaj dolaze otopina Spoja B i vodikov peroksid i kiselina, dok se istodobno hlade, i dok kontinuirano prolaze kroz reaktor.
3. Postupak prema zahtjevu 2 gdje se Spoj C, koji nije izoliran, zaštićuje pivaloil kloridom i bazom radi dobivanja Spoja D.
4. Postupak prema zahtjevu 2 gdje kontinuirani reakcijski postupak obuhvaća protok reakcije kroz zonu niske temperature i zonu visoke temperature pod strogom kontrolom da bi se izbjegao gubitak topline.
5. Postupak prema zahtjevu 4 gdje se temperatura reaktanata u zoni niske temperature održava u rasponu od oko 0-5°C.
6. Postupak prema zahtjevu 4 gdje gdje se temperatura reaktanata u zoni visoke temperature održava u rasponu od oko 12-18°C.
7. Postupak prema zahtjevu 2 gdje se reakcijski tok neutralizira reducensom i podešava pH.
8. Postupak prema zahtjevu 7 gdje se kao reducens koristi natrijev bisulfit.
9. Postupak prema zahtjevu 2 gdje se kao kiselina koristi metansulfonska kiselina.
10. Postupak prema zahtjevu 7 gdje se pH ugašene reakcije kontinuirano podešava između 6.3 i 8.5 pomoću amonijaka.
11. Postupak prema zahtjevu 1 gdje Spoj H reagira s Cbz-L-alaninom u prisutnosti THF-a ili etil acetata i sredstva za vezanje na -5 do 5°C da se dobije Spoj J, s kojeg se zatim uklanja zaštita da se dobije Spoj I.
12. Postupak prema zahtjevu 11 gdje je sredstvo za vezanje EDAC-HCl.
13. Postupak prema zahtjevu 1 gdje se Spoj I kristalizira iz etil acetata/heptana ili butil acetata/heptana.
14. Postupak prema zahtjevu 1 gdje se u koraku e) NaOMe u acetonitrilu i (R)-(+)-propilen oksid u vodi koriste za dobivanje Spoja H.
15. Postupak prema zahtjevu 14 gdje se sa Spoja G uklanja zaštita i zatim reagira s propilen oksidom da se dobije Spoj H.
16. Postupak prema zahtjevu 14 gdje se Spoj H po izboru rekristalizira pomoću acetona i vode.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74530006P | 2006-04-21 | 2006-04-21 | |
| PCT/US2007/066911 WO2007124332A1 (en) | 2006-04-21 | 2007-04-19 | PROCESS FOR THE PREPARATION OF [(1R), 2S]-2-AMINOPROPIONIC ACID 2-[4-(4-FLUORO-2-METHYL-1H-INDOL-5-YLOXY)-5-METHYLPYRROLO[2,1-f][1,2,4]TRIAZIN-6-YLOXY]-1-METHYLETHYL ESTER |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20130099T1 true HRP20130099T1 (hr) | 2013-03-31 |
Family
ID=38357966
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20130099TT HRP20130099T1 (hr) | 2006-04-21 | 2013-02-05 | POSTUPAK PRIPREME [(1R), 2S]-2-AMINOPROPIONSKA KISELINA-2-[4-(4-FLUORO-2-METIL-1H-INDOL-5-ILOKSI)-5-METILPIROLO]2,1-f-[1,2,4-TRIAZIN-6-ILOKSI]-1-METILETIL ESTERA |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US7671199B2 (hr) |
| EP (1) | EP2010538B1 (hr) |
| JP (1) | JP5203353B2 (hr) |
| KR (1) | KR101423789B1 (hr) |
| CN (1) | CN101472927B (hr) |
| AR (1) | AR060622A1 (hr) |
| AU (1) | AU2007240453B2 (hr) |
| BR (1) | BRPI0710691A2 (hr) |
| CA (1) | CA2650059A1 (hr) |
| CL (2) | CL2007001141A1 (hr) |
| DK (1) | DK2010538T3 (hr) |
| EA (1) | EA019693B1 (hr) |
| ES (1) | ES2399379T3 (hr) |
| HR (1) | HRP20130099T1 (hr) |
| IL (1) | IL194715A (hr) |
| MX (1) | MX2008013232A (hr) |
| NO (1) | NO20084326L (hr) |
| PE (1) | PE20080193A1 (hr) |
| PL (1) | PL2010538T3 (hr) |
| PT (1) | PT2010538E (hr) |
| SI (1) | SI2010538T1 (hr) |
| TW (1) | TWI378100B (hr) |
| WO (1) | WO2007124332A1 (hr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007038648A1 (en) * | 2005-09-27 | 2007-04-05 | Bristol-Myers Squibb Company | Crystalline forms of [(1r), 2s]-2-aminopropionic acid 2-[4-(4-fluoro-2-methyl-1h-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-1-methylethyl ester |
| US20120135875A1 (en) * | 2008-02-29 | 2012-05-31 | Bristol-Myers Squibb Company | Methods for determining sensitivity to vascular endothelial growth factor receptor-2 modulators |
| EP2376491B1 (en) | 2008-12-19 | 2015-03-04 | Cephalon, Inc. | Pyrrolotriazines as alk and jak2 inhibitors |
| US11860139B2 (en) | 2018-10-08 | 2024-01-02 | Applied Photophysics Limited | System and method for analysing the composition of a quenched flow reaction liquid |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6982265B1 (en) * | 1999-05-21 | 2006-01-03 | Bristol Myers Squibb Company | Pyrrolotriazine inhibitors of kinases |
| TWI329112B (en) * | 2002-07-19 | 2010-08-21 | Bristol Myers Squibb Co | Novel inhibitors of kinases |
| TWI272271B (en) * | 2002-07-19 | 2007-02-01 | Bristol Myers Squibb Co | Process for preparing certain pyrrolotriazine compounds |
| US7432373B2 (en) * | 2004-06-28 | 2008-10-07 | Bristol-Meyers Squibb Company | Processes and intermediates useful for preparing fused heterocyclic kinase inhibitors |
| US7173031B2 (en) * | 2004-06-28 | 2007-02-06 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
| WO2006130657A2 (en) * | 2005-05-31 | 2006-12-07 | Bristol-Myers Squibb Company | Stereoselective reduction process for the preparation of pyrrolotriazine compounds |
| WO2007038648A1 (en) * | 2005-09-27 | 2007-04-05 | Bristol-Myers Squibb Company | Crystalline forms of [(1r), 2s]-2-aminopropionic acid 2-[4-(4-fluoro-2-methyl-1h-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-1-methylethyl ester |
-
2007
- 2007-04-19 SI SI200731167T patent/SI2010538T1/sl unknown
- 2007-04-19 BR BRPI0710691-2A patent/BRPI0710691A2/pt not_active IP Right Cessation
- 2007-04-19 CN CN2007800232897A patent/CN101472927B/zh active Active
- 2007-04-19 CA CA002650059A patent/CA2650059A1/en not_active Abandoned
- 2007-04-19 KR KR1020087025577A patent/KR101423789B1/ko active IP Right Grant
- 2007-04-19 AU AU2007240453A patent/AU2007240453B2/en not_active Ceased
- 2007-04-19 EP EP07760872A patent/EP2010538B1/en active Active
- 2007-04-19 JP JP2009506761A patent/JP5203353B2/ja not_active Expired - Fee Related
- 2007-04-19 MX MX2008013232A patent/MX2008013232A/es active IP Right Grant
- 2007-04-19 WO PCT/US2007/066911 patent/WO2007124332A1/en active Application Filing
- 2007-04-19 DK DK07760872.7T patent/DK2010538T3/da active
- 2007-04-19 ES ES07760872T patent/ES2399379T3/es active Active
- 2007-04-19 PL PL07760872T patent/PL2010538T3/pl unknown
- 2007-04-19 EA EA200802171A patent/EA019693B1/ru not_active IP Right Cessation
- 2007-04-19 PT PT77608727T patent/PT2010538E/pt unknown
- 2007-04-20 CL CL2007001141A patent/CL2007001141A1/es unknown
- 2007-04-20 TW TW096114144A patent/TWI378100B/zh not_active IP Right Cessation
- 2007-04-20 US US11/737,787 patent/US7671199B2/en active Active
- 2007-04-20 AR ARP070101727A patent/AR060622A1/es unknown
- 2007-04-20 PE PE2007000492A patent/PE20080193A1/es not_active Application Discontinuation
-
2008
- 2008-10-12 IL IL194715A patent/IL194715A/en not_active IP Right Cessation
- 2008-10-16 NO NO20084326A patent/NO20084326L/no not_active Application Discontinuation
-
2010
- 2010-05-28 CL CL2010000554A patent/CL2010000554A1/es unknown
-
2013
- 2013-02-05 HR HRP20130099TT patent/HRP20130099T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL194715A (en) | 2013-10-31 |
| AU2007240453A1 (en) | 2007-11-01 |
| ES2399379T3 (es) | 2013-04-01 |
| CN101472927A (zh) | 2009-07-01 |
| MX2008013232A (es) | 2008-10-21 |
| AR060622A1 (es) | 2008-07-02 |
| JP5203353B2 (ja) | 2013-06-05 |
| US20070249610A1 (en) | 2007-10-25 |
| JP2009534413A (ja) | 2009-09-24 |
| KR20090008246A (ko) | 2009-01-21 |
| EA019693B1 (ru) | 2014-05-30 |
| CL2010000554A1 (es) | 2010-10-15 |
| CN101472927B (zh) | 2012-07-04 |
| US7671199B2 (en) | 2010-03-02 |
| CA2650059A1 (en) | 2007-11-01 |
| DK2010538T3 (da) | 2013-03-18 |
| TW200808799A (en) | 2008-02-16 |
| BRPI0710691A2 (pt) | 2011-08-23 |
| NO20084326L (no) | 2008-11-18 |
| PT2010538E (pt) | 2013-02-22 |
| EP2010538B1 (en) | 2012-12-05 |
| PE20080193A1 (es) | 2008-03-10 |
| EP2010538A1 (en) | 2009-01-07 |
| WO2007124332A1 (en) | 2007-11-01 |
| TWI378100B (en) | 2012-12-01 |
| CL2007001141A1 (es) | 2008-01-18 |
| SI2010538T1 (sl) | 2013-06-28 |
| PL2010538T3 (pl) | 2013-04-30 |
| KR101423789B1 (ko) | 2014-07-30 |
| AU2007240453B2 (en) | 2012-04-12 |
| EA200802171A1 (ru) | 2009-08-28 |
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