KR20140128318A - 1,4-보호된 9-하이드록시-5-옥소-1,4-디아자-스피로 [5.5] 운데칸의 입체선택적 합성 방법 - Google Patents
1,4-보호된 9-하이드록시-5-옥소-1,4-디아자-스피로 [5.5] 운데칸의 입체선택적 합성 방법 Download PDFInfo
- Publication number
- KR20140128318A KR20140128318A KR1020147021922A KR20147021922A KR20140128318A KR 20140128318 A KR20140128318 A KR 20140128318A KR 1020147021922 A KR1020147021922 A KR 1020147021922A KR 20147021922 A KR20147021922 A KR 20147021922A KR 20140128318 A KR20140128318 A KR 20140128318A
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- compound
- optionally
- reaction
- tautomeric
- 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.)
- Withdrawn
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- 238000000034 method Methods 0.000 title claims abstract description 27
- 230000000707 stereoselective effect Effects 0.000 title claims abstract description 7
- 230000015572 biosynthetic process Effects 0.000 title description 6
- 238000003786 synthesis reaction Methods 0.000 title description 6
- CGBQPXGVSMMBHA-UHFFFAOYSA-N 9-hydroxy-1,4-diazaspiro[5.5]undecan-5-one Chemical class C1CC(O)CCC21C(=O)NCCN2 CGBQPXGVSMMBHA-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 35
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 150000003839 salts Chemical group 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
- 239000000543 intermediate Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- -1 2,2,2-trifluoro-acetyl Chemical group 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- YELXTWKVTZTDCM-UHFFFAOYSA-N pentadecan-3-one Chemical compound CCCCCCCCCCCCC(=O)CC YELXTWKVTZTDCM-UHFFFAOYSA-N 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 238000011916 stereoselective reduction Methods 0.000 description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000009904 heterogeneous catalytic hydrogenation reaction Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- WVQMXZJDJKIJCB-UHFFFAOYSA-N spiro[5.5]undecane-4-carboxylic acid Chemical compound C1C(C(=O)O)CCCC11CCCCC1 WVQMXZJDJKIJCB-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- IPSGFPBMDIFDNY-UHFFFAOYSA-N tert-butyl 5,9-dioxo-1-(2,2,2-trifluoroacetyl)-1,4-diazaspiro[5.5]undecane-4-carboxylate Chemical compound O=C1N(C(=O)OC(C)(C)C)CCN(C(=O)C(F)(F)F)C11CCC(=O)CC1 IPSGFPBMDIFDNY-UHFFFAOYSA-N 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12154688.1 | 2012-02-09 | ||
| EP12154688 | 2012-02-09 | ||
| PCT/EP2013/052287 WO2013117568A1 (de) | 2012-02-09 | 2013-02-06 | Verfahren zur stereoselektiven synthese von 1,4-geschützten 9-hydroxy-5-oxo-1,4-diaza-spiro [5.5] undecane |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20140128318A true KR20140128318A (ko) | 2014-11-05 |
Family
ID=47678813
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020147021922A Withdrawn KR20140128318A (ko) | 2012-02-09 | 2013-02-06 | 1,4-보호된 9-하이드록시-5-옥소-1,4-디아자-스피로 [5.5] 운데칸의 입체선택적 합성 방법 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US8629146B2 (enExample) |
| EP (1) | EP2812317B1 (enExample) |
| JP (1) | JP6105631B2 (enExample) |
| KR (1) | KR20140128318A (enExample) |
| CN (1) | CN104080775A (enExample) |
| AU (1) | AU2013218119A1 (enExample) |
| BR (1) | BR112014019196A8 (enExample) |
| CA (1) | CA2862520A1 (enExample) |
| CL (1) | CL2014001823A1 (enExample) |
| EA (1) | EA201400882A1 (enExample) |
| IL (1) | IL233370A (enExample) |
| MX (1) | MX2014009033A (enExample) |
| PH (1) | PH12014501760A1 (enExample) |
| WO (1) | WO2013117568A1 (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2289881A1 (de) * | 2009-08-06 | 2011-03-02 | Boehringer Ingelheim International GmbH | Verfahren zur stereoselektiven Synthese bicyclischer Heterocyclen |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4575507A (en) * | 1985-05-29 | 1986-03-11 | Pfizer Inc. | Spiro-imidazolidines as aldose reductase inhibitors and their pharmaceutical use |
| ATE557008T1 (de) | 2002-03-30 | 2012-05-15 | Boehringer Ingelheim Pharma | 4- ( n-phenylamino ) -chinazoline/chinoline als tyrosinkinaseinhibitoren |
| US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| CA2631813A1 (en) | 2005-12-12 | 2007-06-21 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, medicaments containing said compounds, use thereof, and method for the production thereof |
| PT2245026E (pt) | 2008-02-07 | 2012-10-15 | Boehringer Ingelheim Int | Heterociclos espirocíclicos, produtos farmacêuticos contendo estes compostos, sua utilização e processo para a sua preparação |
| EP2289881A1 (de) | 2009-08-06 | 2011-03-02 | Boehringer Ingelheim International GmbH | Verfahren zur stereoselektiven Synthese bicyclischer Heterocyclen |
| PE20141012A1 (es) * | 2011-02-01 | 2014-09-10 | Boehringer Ingelheim Int | Dimaleato de 9-[4-(3-cloro-2-fluoro-fenilamino)-7-metoxi-quinazolin-6-iloxi]-1,4-diaza-espiro[5.5]undecan-5-ona, su uso como medicamento y su preparacion |
-
2013
- 2013-02-06 JP JP2014556029A patent/JP6105631B2/ja active Active
- 2013-02-06 KR KR1020147021922A patent/KR20140128318A/ko not_active Withdrawn
- 2013-02-06 EP EP13703045.8A patent/EP2812317B1/de active Active
- 2013-02-06 CA CA2862520A patent/CA2862520A1/en not_active Abandoned
- 2013-02-06 MX MX2014009033A patent/MX2014009033A/es not_active Application Discontinuation
- 2013-02-06 WO PCT/EP2013/052287 patent/WO2013117568A1/de not_active Ceased
- 2013-02-06 EA EA201400882A patent/EA201400882A1/ru unknown
- 2013-02-06 BR BR112014019196A patent/BR112014019196A8/pt not_active IP Right Cessation
- 2013-02-06 CN CN201380006918.0A patent/CN104080775A/zh active Pending
- 2013-02-06 AU AU2013218119A patent/AU2013218119A1/en not_active Abandoned
- 2013-02-07 US US13/761,211 patent/US8629146B2/en active Active
-
2014
- 2014-06-25 IL IL233370A patent/IL233370A/en not_active IP Right Cessation
- 2014-07-09 CL CL2014001823A patent/CL2014001823A1/es unknown
- 2014-08-05 PH PH12014501760A patent/PH12014501760A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP2812317B1 (de) | 2016-02-03 |
| BR112014019196A8 (pt) | 2017-07-11 |
| PH12014501760B1 (en) | 2014-11-10 |
| US8629146B2 (en) | 2014-01-14 |
| BR112014019196A2 (enExample) | 2017-06-20 |
| WO2013117568A1 (de) | 2013-08-15 |
| EP2812317A1 (de) | 2014-12-17 |
| CN104080775A (zh) | 2014-10-01 |
| CA2862520A1 (en) | 2013-08-15 |
| US20130211081A1 (en) | 2013-08-15 |
| EA201400882A1 (ru) | 2015-01-30 |
| JP6105631B2 (ja) | 2017-03-29 |
| AU2013218119A1 (en) | 2014-07-17 |
| IL233370A (en) | 2015-04-30 |
| IL233370A0 (en) | 2014-08-31 |
| PH12014501760A1 (en) | 2014-11-10 |
| MX2014009033A (es) | 2014-10-17 |
| CL2014001823A1 (es) | 2015-03-06 |
| JP2015506966A (ja) | 2015-03-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20140805 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |