JP2018508549A5 - - Google Patents
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- JP2018508549A5 JP2018508549A5 JP2017549057A JP2017549057A JP2018508549A5 JP 2018508549 A5 JP2018508549 A5 JP 2018508549A5 JP 2017549057 A JP2017549057 A JP 2017549057A JP 2017549057 A JP2017549057 A JP 2017549057A JP 2018508549 A5 JP2018508549 A5 JP 2018508549A5
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- reaction step
- xxix
- reacting
- 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.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims 73
- 238000000034 method Methods 0.000 claims 20
- -1 allyl halide Chemical class 0.000 claims 10
- 229910052739 hydrogen Inorganic materials 0.000 claims 10
- 239000001257 hydrogen Substances 0.000 claims 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 6
- 239000002253 acid Substances 0.000 claims 6
- 239000002904 solvent Substances 0.000 claims 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 5
- 229930013930 alkaloid Natural products 0.000 claims 5
- 150000003797 alkaloid derivatives Chemical class 0.000 claims 5
- 150000002431 hydrogen Chemical class 0.000 claims 5
- 238000002360 preparation method Methods 0.000 claims 5
- 241000157855 Cinchona Species 0.000 claims 4
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims 4
- 239000003054 catalyst Substances 0.000 claims 4
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims 4
- 229910052763 palladium Inorganic materials 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 claims 4
- 150000003335 secondary amines Chemical class 0.000 claims 4
- 238000011282 treatment Methods 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 206010052428 Wound Diseases 0.000 claims 3
- 208000027418 Wounds and injury Diseases 0.000 claims 3
- 230000001684 chronic effect Effects 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 230000035876 healing Effects 0.000 claims 3
- 238000010438 heat treatment Methods 0.000 claims 3
- 239000012022 methylating agents Substances 0.000 claims 3
- 230000001737 promoting effect Effects 0.000 claims 3
- 230000029663 wound healing Effects 0.000 claims 3
- 241000156724 Antirhea Species 0.000 claims 2
- 235000021513 Cinchona Nutrition 0.000 claims 2
- 235000001258 Cinchona calisaya Nutrition 0.000 claims 2
- 201000003883 Cystic fibrosis Diseases 0.000 claims 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims 2
- 206010069351 acute lung injury Diseases 0.000 claims 2
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 claims 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims 2
- 210000000748 cardiovascular system Anatomy 0.000 claims 2
- 210000004072 lung Anatomy 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 230000000269 nucleophilic effect Effects 0.000 claims 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims 2
- 229960001404 quinidine Drugs 0.000 claims 2
- 229960000948 quinine Drugs 0.000 claims 2
- 239000012453 solvate Substances 0.000 claims 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 claims 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- 206010014561 Emphysema Diseases 0.000 claims 1
- 241001274216 Naso Species 0.000 claims 1
- 238000001237 Raman spectrum Methods 0.000 claims 1
- 238000002441 X-ray diffraction Methods 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 201000009267 bronchiectasis Diseases 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 239000013078 crystal Substances 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 239000012024 dehydrating agents Substances 0.000 claims 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000012074 organic phase Substances 0.000 claims 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 claims 1
- 0 C*S(c1cc(C#N)ccc1C1N(*)C2OC2N(c2cc(C)ccc2)C(C)=C1C(O*)=*)(=*)=O Chemical compound C*S(c1cc(C#N)ccc1C1N(*)C2OC2N(c2cc(C)ccc2)C(C)=C1C(O*)=*)(=*)=O 0.000 description 1
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2021081100A JP7117415B2 (ja) | 2015-03-18 | 2021-05-12 | （４ｓ）－４－［４－シアノ－２－（メチルスルホニル）フェニル］－３，６－ジメチル－２－オキソ－１－［３－（トリフルオロメチル）フェニル］－１，２，３，４－テトラヒドロピリミジン－５－カルボニトリルの製造方法 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15159570 | 2015-03-18 | ||
| EP15159570.9 | 2015-03-18 | ||
| PCT/EP2016/055498 WO2016146607A1 (de) | 2015-03-18 | 2016-03-15 | Verfahren zur herstellung von (4s)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluormethyl)phenyl]-1,2,3,4-tetrahydro pyrimidin-5-carbonitril |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020115899A Division JP7125450B2 (ja) | 2015-03-18 | 2020-07-03 | （４ｓ）－４－［４－シアノ－２－（メチルスルホニル）フェニル］－３，６－ジメチル－２－オキソ－１－［３－（トリフルオロメチル）フェニル］－１，２，３，４－テトラヒドロピリミジン－５－カルボニトリルの製造方法 |
| JP2021081100A Division JP7117415B2 (ja) | 2015-03-18 | 2021-05-12 | （４ｓ）－４－［４－シアノ－２－（メチルスルホニル）フェニル］－３，６－ジメチル－２－オキソ－１－［３－（トリフルオロメチル）フェニル］－１，２，３，４－テトラヒドロピリミジン－５－カルボニトリルの製造方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018508549A JP2018508549A (ja) | 2018-03-29 |
| JP2018508549A5 true JP2018508549A5 (https=) | 2019-04-25 |
| JP7390100B2 JP7390100B2 (ja) | 2023-12-01 |
Family
ID=52684127
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017549057A Active JP7390100B2 (ja) | 2015-03-18 | 2016-03-15 | （４ｓ）－４－［４－シアノ－２－（メチルスルホニル）フェニル］－３，６－ジメチル－２－オキソ－１－［３－（トリフルオロメチル）フェニル］－１，２，３，４－テトラヒドロピリミジン－５－カルボニトリルの製造方法 |
| JP2020115899A Active JP7125450B2 (ja) | 2015-03-18 | 2020-07-03 | （４ｓ）－４－［４－シアノ－２－（メチルスルホニル）フェニル］－３，６－ジメチル－２－オキソ－１－［３－（トリフルオロメチル）フェニル］－１，２，３，４－テトラヒドロピリミジン－５－カルボニトリルの製造方法 |
| JP2021081100A Expired - Fee Related JP7117415B2 (ja) | 2015-03-18 | 2021-05-12 | （４ｓ）－４－［４－シアノ－２－（メチルスルホニル）フェニル］－３，６－ジメチル－２－オキソ－１－［３－（トリフルオロメチル）フェニル］－１，２，３，４－テトラヒドロピリミジン－５－カルボニトリルの製造方法 |
| JP2022128861A Pending JP2022145951A (ja) | 2015-03-18 | 2022-08-12 | （４ｓ）－４－［４－シアノ－２－（メチルスルホニル）フェニル］－３，６－ジメチル－２－オキソ－１－［３－（トリフルオロメチル）フェニル］－１，２，３，４－テトラヒドロピリミジン－５－カルボニトリルの製造方法 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020115899A Active JP7125450B2 (ja) | 2015-03-18 | 2020-07-03 | （４ｓ）－４－［４－シアノ－２－（メチルスルホニル）フェニル］－３，６－ジメチル－２－オキソ－１－［３－（トリフルオロメチル）フェニル］－１，２，３，４－テトラヒドロピリミジン－５－カルボニトリルの製造方法 |
| JP2021081100A Expired - Fee Related JP7117415B2 (ja) | 2015-03-18 | 2021-05-12 | （４ｓ）－４－［４－シアノ－２－（メチルスルホニル）フェニル］－３，６－ジメチル－２－オキソ－１－［３－（トリフルオロメチル）フェニル］－１，２，３，４－テトラヒドロピリミジン－５－カルボニトリルの製造方法 |
| JP2022128861A Pending JP2022145951A (ja) | 2015-03-18 | 2022-08-12 | （４ｓ）－４－［４－シアノ－２－（メチルスルホニル）フェニル］－３，６－ジメチル－２－オキソ－１－［３－（トリフルオロメチル）フェニル］－１，２，３，４－テトラヒドロピリミジン－５－カルボニトリルの製造方法 |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US10316001B2 (https=) |
| EP (1) | EP3271337B1 (https=) |
| JP (4) | JP7390100B2 (https=) |
| KR (1) | KR20170129191A (https=) |
| CN (2) | CN110981815A (https=) |
| AU (1) | AU2016232270B2 (https=) |
| CA (1) | CA2980071A1 (https=) |
| ES (1) | ES2877583T3 (https=) |
| WO (1) | WO2016146607A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110981815A (zh) | 2015-03-18 | 2020-04-10 | Ph制药有限公司 | 用于生产化合物的方法 |
| CA3101274A1 (en) * | 2018-04-24 | 2019-10-31 | Ph Pharma Co., Ltd. | Use of neutrophil elastase inhibitors in liver disease |
| TW202122086A (zh) * | 2019-08-23 | 2021-06-16 | 韓商Ｐｈ製藥公司 | 嗜中性白血球彈性蛋白酶抑制劑在肺部疾病中之使用 |
| CN112304919B (zh) * | 2020-09-18 | 2022-07-05 | 公安部物证鉴定中心 | 一种乌头碱类植物毒素的定性定量检测方法 |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9214053D0 (en) | 1992-07-02 | 1992-08-12 | Ici Plc | Heterocyclic amides |
| US6372936B1 (en) * | 1999-06-09 | 2002-04-16 | Eli Lilly And Company | Optical resolution of aminoisobobutyric acid |
| MY125533A (en) | 1999-12-06 | 2006-08-30 | Bristol Myers Squibb Co | Heterocyclic dihydropyrimidine compounds |
| GB0219896D0 (en) | 2002-08-27 | 2002-10-02 | Bayer Ag | Dihydropyridine derivatives |
| GB0220962D0 (en) * | 2002-09-10 | 2002-10-23 | Bayer Ag | Heterocyclic derivatives |
| EP1546113B1 (en) | 2002-09-10 | 2013-05-01 | Bayer Intellectual Property GmbH | Pyrimidinone derivatives as therapeutic agents against acute and chronic inflammatory, ischaemic and remodelling processes |
| US7566723B2 (en) | 2002-09-10 | 2009-07-28 | Bayer Healthcare Ag | 1-phenyl1-3,4-dihydropyrimidin-2(1H)-one derivatives and their use |
| WO2004052858A2 (en) | 2002-12-06 | 2004-06-24 | Eli Lilly And Company | Inhibitors of monoamine uptake |
| US7166603B2 (en) | 2003-07-23 | 2007-01-23 | Bristol-Myers Squibb Co. | Dihydropyrimidone inhibitors of calcium channel function |
| ES2428503T3 (es) | 2004-02-26 | 2013-11-08 | Bayer Intellectual Property Gmbh | 1,4-Diaril-dihidropirimidin-2-onas y su uso como inhibidores de elastasa de neutrófilos humanos |
| CA2557271C (en) | 2004-02-26 | 2012-08-21 | Bayer Healthcare Ag | 1,4-diaryl-dihydropyrimidin-2-ones and their use as human neutrophil elastase inhibitors |
| GB0502258D0 (en) | 2005-02-03 | 2005-03-09 | Argenta Discovery Ltd | Compounds and their use |
| GB0512940D0 (en) | 2005-06-24 | 2005-08-03 | Argenta Discovery Ltd | Compounds and their use |
| GB0520743D0 (en) | 2005-10-12 | 2005-11-23 | Argenta Discovery Ltd | Compounds and their use |
| CA2629807A1 (en) * | 2005-12-05 | 2007-06-14 | Wyeth | Process for preparing substituted aryl cycloalkanol derivatives |
| NZ572250A (en) | 2006-05-04 | 2011-10-28 | Pulmagen Therapeutics Inflammation Ltd | Tetrahydropyrrolopyrimidinediones and their use as human neutrophil elastase inhibitors |
| US20100010024A1 (en) | 2006-07-01 | 2010-01-14 | Bayer Healthcare Ag | Use of1,4-diaryl-dihydropyrimidine-2-on derivatives for treating pulmonary arterial hypertension |
| US20110003858A1 (en) | 2006-09-04 | 2011-01-06 | Bergstroem Lena | Multimeric heterocyclic compounds useful as neutrophil elastase inhibitors |
| DE102008022521A1 (de) | 2008-05-07 | 2009-11-12 | Bayer Schering Pharma Aktiengesellschaft | 1,4-Diaryl-pyrimidopyridazin-2,5-dione und ihre Verwendung |
| US8288402B2 (en) * | 2007-12-20 | 2012-10-16 | Bayer Intellectual Property Gmbh | 4-(4-cyano-2-thioaryl)dihydropyrimidinones and their use |
| DE102009016553A1 (de) | 2009-04-06 | 2010-10-07 | Bayer Schering Pharma Aktiengesellschaft | Sulfonamid- und Sulfoximin-substituierte Diaryldihydropyrimidinone und ihre Verwendung |
| CN110981815A (zh) | 2015-03-18 | 2020-04-10 | Ph制药有限公司 | 用于生产化合物的方法 |
-
2016
- 2016-03-15 CN CN201911315571.3A patent/CN110981815A/zh active Pending
- 2016-03-15 ES ES16713747T patent/ES2877583T3/es active Active
- 2016-03-15 KR KR1020177029441A patent/KR20170129191A/ko not_active Ceased
- 2016-03-15 JP JP2017549057A patent/JP7390100B2/ja active Active
- 2016-03-15 AU AU2016232270A patent/AU2016232270B2/en not_active Ceased
- 2016-03-15 CN CN201680028214.7A patent/CN107635972A/zh active Pending
- 2016-03-15 CA CA2980071A patent/CA2980071A1/en active Pending
- 2016-03-15 US US15/559,385 patent/US10316001B2/en active Active
- 2016-03-15 WO PCT/EP2016/055498 patent/WO2016146607A1/de not_active Ceased
- 2016-03-15 EP EP16713747.0A patent/EP3271337B1/de active Active
-
2019
- 2019-04-25 US US16/394,811 patent/US10676443B2/en active Active
-
2020
- 2020-07-03 JP JP2020115899A patent/JP7125450B2/ja active Active
-
2021
- 2021-05-12 JP JP2021081100A patent/JP7117415B2/ja not_active Expired - Fee Related
-
2022
- 2022-08-12 JP JP2022128861A patent/JP2022145951A/ja active Pending
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