JP2018508549A5 - - Google Patents
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- Publication number
- 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
Links
- 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 |
|---|---|---|---|
| EP15159570.9 | 2015-03-18 | ||
| EP15159570 | 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 (enExample) | 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 Active 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 Active 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 (enExample) |
| EP (1) | EP3271337B1 (enExample) |
| JP (4) | JP7390100B2 (enExample) |
| KR (1) | KR20170129191A (enExample) |
| CN (2) | CN110981815A (enExample) |
| AU (1) | AU2016232270B2 (enExample) |
| CA (1) | CA2980071A1 (enExample) |
| ES (1) | ES2877583T3 (enExample) |
| WO (1) | WO2016146607A1 (enExample) |
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 |
| EP3784657A4 (en) * | 2018-04-24 | 2022-02-09 | pH Pharma Co., Ltd. | USE OF NEUTROPHIL ELASTASE INHIBITORS IN LIVER DISEASE |
| EP4017497A4 (en) * | 2019-08-23 | 2024-01-10 | pH Pharma Co., Ltd. | USE OF A NEUTROPHIL ELASTASE INHIBITOR IN LUNG DISEASES |
| 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 |
| WO2004024701A1 (en) | 2002-09-10 | 2004-03-25 | Bayer Healthcare Ag | Heterocyclic derivatives |
| PL375647A1 (en) | 2002-09-10 | 2005-12-12 | Bayer Healthcare Ag | Pyrimidinone derivatives as therapeutic agents against acute and chronic inflammatory, ischaemic and remodelling processes |
| GB0220962D0 (en) * | 2002-09-10 | 2002-10-23 | Bayer Ag | Heterocyclic derivatives |
| AU2003290735A1 (en) | 2002-12-06 | 2004-06-30 | 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 |
| WO2005082863A2 (en) | 2004-02-26 | 2005-09-09 | Bayer Healthcare Ag | 1,4 diaryl-dihydropyrimidin-2 ones and their use as a human neutrophil elastase inhibitors |
| ES2394177T3 (es) | 2004-02-26 | 2013-01-23 | Bayer Intellectual Property Gmbh | 1,4-diaril-dihidropirimidin-2-onas y su uso como inhibidores de elastasa de neutrófilos humanos |
| 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 |
| WO2007067575A2 (en) | 2005-12-05 | 2007-06-14 | Wyeth | Process for preparing substituted aryl cycloalkanol derivatives |
| JP4999920B2 (ja) | 2006-05-04 | 2012-08-15 | プルマジェン セラピューティクス （インフラメーション） リミテッド | テトラヒドロピロロピリミジンジオン類およびヒト好中球エラスターゼ阻害薬としてのそれらの使用 |
| US20100010024A1 (en) | 2006-07-01 | 2010-01-14 | Bayer Healthcare Ag | Use of1,4-diaryl-dihydropyrimidine-2-on derivatives for treating pulmonary arterial hypertension |
| EP2064184A1 (en) | 2006-09-04 | 2009-06-03 | AstraZeneca AB | Multimeric heterocyclic compounds useful as neutrophil elastase inhibitors |
| MX2010006033A (es) | 2007-12-20 | 2010-07-16 | Bayer Schering Pharma Ag | 4-(4-ciano-2-tioaril)dihidropirimidinonas y su uso. |
| DE102008022521A1 (de) | 2008-05-07 | 2009-11-12 | Bayer Schering Pharma Aktiengesellschaft | 1,4-Diaryl-pyrimidopyridazin-2,5-dione und ihre Verwendung |
| 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 |
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2016
- 2016-03-15 CN CN201911315571.3A patent/CN110981815A/zh active Pending
- 2016-03-15 JP JP2017549057A patent/JP7390100B2/ja active Active
- 2016-03-15 KR KR1020177029441A patent/KR20170129191A/ko not_active Ceased
- 2016-03-15 ES ES16713747T patent/ES2877583T3/es active Active
- 2016-03-15 WO PCT/EP2016/055498 patent/WO2016146607A1/de not_active Ceased
- 2016-03-15 AU AU2016232270A patent/AU2016232270B2/en not_active Ceased
- 2016-03-15 US US15/559,385 patent/US10316001B2/en active Active
- 2016-03-15 CA CA2980071A patent/CA2980071A1/en active Pending
- 2016-03-15 EP EP16713747.0A patent/EP3271337B1/de active Active
- 2016-03-15 CN CN201680028214.7A patent/CN107635972A/zh active Pending
-
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 active Active
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2022
- 2022-08-12 JP JP2022128861A patent/JP2022145951A/ja active Pending