HRP20141148T1 - Postupak proizvodnje i rastvaranja 2-acilamino-3-difenilpropanske kiseline - Google Patents
Postupak proizvodnje i rastvaranja 2-acilamino-3-difenilpropanske kiseline Download PDFInfo
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- HRP20141148T1 HRP20141148T1 HRP20141148AT HRP20141148T HRP20141148T1 HR P20141148 T1 HRP20141148 T1 HR P20141148T1 HR P20141148A T HRP20141148A T HR P20141148AT HR P20141148 T HRP20141148 T HR P20141148T HR P20141148 T1 HRP20141148 T1 HR P20141148T1
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- 238000000034 method Methods 0.000 title claims 26
- 238000004519 manufacturing process Methods 0.000 title claims 13
- 239000002253 acid Substances 0.000 title claims 4
- 150000001875 compounds Chemical class 0.000 claims 34
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 10
- 150000003839 salts Chemical class 0.000 claims 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 9
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 5
- 229910052736 halogen Inorganic materials 0.000 claims 5
- 150000002367 halogens Chemical class 0.000 claims 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 5
- 125000001424 substituent group Chemical group 0.000 claims 5
- 150000001412 amines Chemical class 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- 238000006114 decarboxylation reaction Methods 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- 239000001257 hydrogen Substances 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
- 239000012445 acidic reagent Substances 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims 2
- 150000002148 esters Chemical class 0.000 claims 2
- 238000010438 heat treatment Methods 0.000 claims 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 1
- 235000011054 acetic acid Nutrition 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 229940117389 dichlorobenzene Drugs 0.000 claims 1
- 238000004090 dissolution Methods 0.000 claims 1
- 235000019253 formic acid Nutrition 0.000 claims 1
- 150000007522 mineralic acids Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 235000006408 oxalic acid Nutrition 0.000 claims 1
- 235000011007 phosphoric acid Nutrition 0.000 claims 1
- 238000010992 reflux Methods 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 239000008096 xylene Substances 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/16—Preparation of optical isomers
- C07C231/20—Preparation of optical isomers by separation of optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/47—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/82—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/87—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (21)
1. Postupak za proizvodnju spoja formule (III) ili njegove soli,
[image]
gdje
R1 je C1-C7-alkil, kao što je metil ili etil; ili je nesupstituirani C6-C10-aril kao što je fenil; ili je C6-C10-aril supstituiran s jednim ili više supstituenata neovisno odabranih od sljedećih:
C1-C7-alkil, C1-C7-alkoksi-C1-C7-alkil, C1-C7-alkoksi ili halogen, kao što je para-klorofenil;
naznačen time, da se sastoji od
reakcije spoja formule (IV) ili njegove soli,
[image]
gdje R1 je kao što je definiran za spoj formule (III),
pod uvjetima dekarboksilacijske reakcije koja se postiže zagrijavanjem,
u svrhu dobivanja spoja formule (III).
2. Postupak prema zahtjevu 1, naznačen time, da se uvjeti za dekarboksilacijsku reakciju postižu zagrijavanjem na temperaturi od 80°C do 250°C.
3. Postupak prema zahtjevu 2, naznačen time, da se dekarboksilacijska reakcija provodi u otapalu odabranom od sljedećih: voda, toluen, ksilen, etilbenzen, klorobenzen, diklorobenzen, nitrobenzen, N,N-dimetil-formamid (DMF) i 1-metil-2-pirolidon (NMP) te na temperaturi refluksa navedenog otapala.
4. Postupak za proizvodnju kiralnog spoja formule (II),
[image]
gdje
R1 je C1-C7-alkil, kao što je metil ili etil; ili je nesupstituirani C6-C10-aril kao što je fenil; ili je C6-C10-aril supstituiran s jednim ili više supstituenata neovisno odabranih od sljedećih:
C1-C7-alkil, C1-C7-alkoksi-C1-C7-alkil, C1-C7-alkoksi ili halogen, kao što je para-klorofenil;
R2 je C1-C7-alkil, kao što je metil; ili je R3R4NC(=O)- ili R5OC(=O)-, pri čemu su R3 i R4 neovisno odabrani od vodika ili C1-C7-alkila; i R5 je C1-C7-alkil;
R6 je C6-C10-aril, kao što je fenil, i
“*” znači kiralni centar s apsolutnom stereokemijom (R) ili (S),
naznačen time, da se sastoji od
reakcije spoja formule (III) ili njegove soli,
[image]
gdje je R1 kao što je definiran za formulu (II), s kiralnim aminom formule (V)
[image]
gdje su R2 i R6 kao što su definirani za spoj formule (II), i
“*” znači kiralni centar s apsolutnom stereokemijom (R) ili (S);
te od rastavaranja rezultirajuće dijastereomerne smjese putem kristalizacije,
za dobivanje spoja formule (II).
5. Postupak prema zahtjevu 4, naznačen time, da kiralni amin formule (V) ima formulu (Va):
[image]
ili
formulu (Vb):
[image]
pri čemu su R2 i R6 kao što su definirani u zahtjevu 3.
6. Postupak prema zahtjevu 4, naznačen time, da kiralni spoj formule (II) ima formula:
[image]
[image]
[image]
ili
[image]
pri čemu su R1, R2 i R6 kao što su definirani u zahtjevu 3.
7. Postupak prema zahtjevu 4, naznačen time, da kiralni spoj formule (II) ima formulu (IIa):
[image]
pri čemu su R1, R2 i R6 kao što su definirani u zahtjevu 3; i
kiralni amin formule (V) ima formulu (Va):
[image]
pri čemu su R1, R2 i R6 kao što su definirani u zahtjevu 3.
8. Postupak prema zahtjevu 4, naznačen time, da kiralni spoj formule (II) ima formulu (IIb):
[image]
pri čemu su R1, R2 i R6 kao što su definirani u zahtjevu 3; i
kiralni amin formule (V) ima formulu (Vb):
[image]
pri čemu su R2 i R6 kao što su definirani u zahtjevu 3.
9. Postupak za proizvodnju spoja formule (I) ili njegove soli,
[image]
gdje
R1 je C1-C7-alkil, kao što je metil ili etil; ili je nesupstituirani C6-C10-aril kao što je fenil; ili je C6-C10-aril supstituiran s jednim ili više supstituenata neovisno odabranih od sljedećih:
C1-C7-alkil, C1-C7-alkoksi-C1-C7-alkil, C1-C7-alkoksi ili halogen, kao što je para-klorofenil; i
“*” znači kiralni centar s apsolutnom stereokemijom (R) ili (S),
naznačen time, da se sastoji od
obrade spoja formule (II),
[image]
gdje
R1 je C1-C7-alkil, kao što je metil ili etil; ili je nesupstituirani C6-C10-aril kao što je fenil; ili je C6-C10-aril supstituiran s jednim ili više supstituenata neovisno odabranih od sljedećih:
C1-C7-alkil, C1-C7-alkoksi-C1-C7-alkil, C1-C7-alkoksi ili halogen, kao što je para-klorofenil;
R2 je C1-C7-alkil, kao što je metil; ili je R3R4NC(=O)- ili R5OC(=O)-, pri čemu su R3 i R4 neovisno odabrani od vodika ili C1-C7-alkila; i R5 je C1-C7-alkil;
R6 je C6-C10-aril, kao što je fenil, i
“*” znači kiralni centar s apsolutnom stereokemijom (R) ili (S),
s kiselinskim reagensom,
za dobivanje spoja formule (I).
10. Postupak prema zahtjevu 9, naznačen time, da kiselinski reagens je anorganska kiselina ili organska kiselina, kao što je klorovodična kiselina, sumporna kiselina, fosforna kiselina, oksalna kiselina, limunska kiselina, mravlja kiselina ili octena kiselina.
11. Postupak prema zahtjevima 9 ili 10, naznačen time, da kiralni spoj formule (I) ima formulu (Ia):
[image]
pri čemu je R1 kao što je definiran u zahtjevu 8; i
kiralni spoj formule (II) ima formulu (IIa):
[image]
pri čemu su R1, R2 i R6 kao što su definirani u zahtjevu 8.
12. Postupak prema zahtjevima 9 ili 10, naznačen time, da kiralni spoj formule (I) ima formulu (Ib):
[image]
pri čemu je R1 kao što je definiran u zahtjevu 8;
kiralni spoj formule (II) ima formulu (IIb):
[image]
pri čemu su R1, R2 i R6 kao što su definirani u zahtjevu 8.
13. Postupak za proizvodnju spoja formule (I), prema zahtjevu 9, naznačen time, da obuhvaća sljedeće korake:
proizvodnja spoja formule (III) prema zahtjevu 1, prema postupku definiranom u zahtjevima 1, 2 ili 3;
proizvodnja spoja formule (II) prema zahtjevu 4, prema bilo kojem postupku definiranom u zahtjevima 4 do 8, poželjno prema postupku definiranom u zahtjevu 7; i
dobivanje spoja formule (I), prema bilo kojem postupku definiranom u zahtjevima 9 do 12, poželjno prema postupku definiranom u zahtjevu 11.
14. Postupak za proizvodnju spoja formule (I), prema zahtjevu 9, naznačen time, da obuhvaća sljedeće korake:
proizvodnja spoja formule (II) prema zahtjevu 4, prema bilo kojem postupku definiranom u zahtjevima 4 do 8, poželjno prema postupku definiranom u zahtjevu 7; i
dobivanje spoja formule (I), prema bilo kojem postupku definiranom u zahtjevima 9 do 12, poželjno prema postupku definiranom u zahtjevu 11.
15. Kiralni spoj, naznačen time, da ima formulu (II)
[image]
gdje
R1 je C1-C7-alkil, kao što je metil ili etil; ili je nesupstituirani C6-C10-aril kao što je fenil; ili je C6-C10-aril supstituiran s jednim ili više supstituenata neovisno odabranih od sljedećih:
C1-C7-alkil, C1-C7-alkoksi-C1-C7-alkil, C1-C7-alkoksi ili halogen, kao što je para-klorofenil;
R2 je C1-C7-alkil, kao što je metil; ili je R3R4NC(=O)- ili R5OC(=O)-, pri čemu su R3 i R4 neovisno odabrani od vodika ili C1-C7-alkila; i R5 je C1-C7-alkil;
R6 je C6-C10-aril, kao što je fenil, i
“*” znači kiralni centar s apsolutnom stereokemijom (R) ili (S),
pri čemu poželjno spoj formule (II) ima formulu (IIa) ili (IIb):
[image]
[image]
gdje su R1, R2 i R6 kao što su gore definirani.
16. Spoj prema zahtjevu 15, naznačen time, da R6 je fenil.
17. Uporaba spoja prema zahtjevima 15 ili 16, naznačena time, da je za sintezu spoja koji u kralježnici sadrži γ-amino-δ-bifenil-α-metilalkanoinsku kiselinu, ili ester γ-amino-δ-bifenil-α-metilalkanoinske kiseline.
18. Uporaba prema zahtjevu 17, naznačena time, da spoj je N-(3-karboksi-1-oksopropil)-(4S)-(p-fenilfenilmetil)-4-amino-(2R)-metil-butanska kiselina ili njezina sol ili ester te kiseline.
19. Uporaba prema zahtjevu 17, naznačena time, da spoj je N-(3-karboksi-1-oksopropil)-(4S)-p-fenilfenilmetil)-4-amino-(2R)-metil-butanska kiselina-etilester ili njegova sol.
20. Postupak proizvodnje N-(3-karboksil-1-oksopropil)-(4S)-p-fenilfenilmetil)-4-amino-(2R)-metil-butanska kiselina-etilestera ili njegove soli, naznačen time, da obuhvaća proizvodnju spoja formule (II) ili njegove soli, kao što je definirano u zahtjevima 15 ili 16.
21. Postupak proizvodnje N-(3-karboksil-1-oksopropil)-(4S)-p-fenilfenilmetil)-4-amino-(2R)-metil-butanska kiselina-etilestera ili njegove soli, naznačen time, da obuhvaća proizvodnju spoja formule (IIa) ili njegove soli, kao što je definirano u zahtjevima 15 ili 16.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910045210A CN101774941A (zh) | 2009-01-13 | 2009-01-13 | 2-酰基氨基-3-联苯基丙酸的制备及拆分方法 |
| PCT/CN2010/070144 WO2010081410A1 (en) | 2009-01-13 | 2010-01-12 | Process for manufacture and resolution of 2-acylamino-3-diphenylpropanoic acid |
| EP10731044.3A EP2387558B1 (en) | 2009-01-13 | 2010-01-12 | Process for manufacture and resolution of 2-acylamino-3-diphenylpropanoic acid |
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| Publication Number | Publication Date |
|---|---|
| HRP20141148T1 true HRP20141148T1 (hr) | 2015-01-30 |
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| Application Number | Title | Priority Date | Filing Date |
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| HRP20141148AT HRP20141148T1 (hr) | 2009-01-13 | 2014-11-25 | Postupak proizvodnje i rastvaranja 2-acilamino-3-difenilpropanske kiseline |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US8703990B2 (hr) |
| EP (1) | EP2387558B1 (hr) |
| JP (1) | JP5687205B2 (hr) |
| KR (1) | KR101699095B1 (hr) |
| CN (4) | CN101774941A (hr) |
| AU (1) | AU2010205973B2 (hr) |
| BR (1) | BRPI1007367A2 (hr) |
| CA (1) | CA2749092C (hr) |
| ES (1) | ES2524971T3 (hr) |
| HR (1) | HRP20141148T1 (hr) |
| MX (1) | MX2011007445A (hr) |
| PL (1) | PL2387558T3 (hr) |
| PT (1) | PT2387558E (hr) |
| RU (1) | RU2520215C2 (hr) |
| SI (1) | SI2387558T1 (hr) |
| WO (1) | WO2010081410A1 (hr) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101684077B (zh) | 2008-09-24 | 2013-01-02 | 浙江九洲药业股份有限公司 | N-酰基联苯丙氨酸的制备方法 |
| CN101774941A (zh) * | 2009-01-13 | 2010-07-14 | 浙江九洲药业股份有限公司 | 2-酰基氨基-3-联苯基丙酸的制备及拆分方法 |
| KR20120093227A (ko) * | 2009-09-23 | 2012-08-22 | 노파르티스 아게 | Ｎ-아실비페닐 알라닌의 제조 방법 |
| EP2744779A1 (en) * | 2011-08-19 | 2014-06-25 | DSM IP Assets B.V. | Synthesis of r-biphenylalaninol |
| CN102952029B (zh) * | 2011-09-30 | 2015-07-08 | 北京海步国际医药科技发展有限公司 | 将苄胺衍生物用于拆分2-羟基-3-甲氧基-3,3-二-苯基丙酸消旋物及拆分方法 |
| CN105085321B (zh) * | 2012-03-07 | 2017-11-24 | 浙江九洲药业股份有限公司 | 一种n‑甲氧羰基‑l‑叔亮氨酸的制备方法 |
| WO2016037098A1 (en) | 2014-09-04 | 2016-03-10 | Concert Pharmaceuticals, Inc. | Deuterated sacubitril |
| TW201632493A (zh) | 2015-02-13 | 2016-09-16 | 諾華公司 | 新穎方法 |
| CN105017082B (zh) * | 2015-07-31 | 2017-09-19 | 上海皓元医药股份有限公司 | 一种心衰药Entresto 关键中间体(R)‑叔丁基 (1‑([1,1`‑联苯]‑4‑基)‑3‑羟基丙烷‑2‑基)氨基甲酸酯的制备方法 |
| CN105085322B (zh) * | 2015-08-15 | 2017-10-03 | 浙江永宁药业股份有限公司 | Ahu‑377中间体的制备方法及其中间体和中间体的制备方法 |
| CN105168205A (zh) * | 2015-08-18 | 2015-12-23 | 泰力特医药（湖北）有限公司 | 一种血管紧张素ii受体和脑啡肽酶受体双重抑制剂lcz696的制备方法 |
| WO2017051326A1 (en) | 2015-09-23 | 2017-03-30 | Novartis Ag | New processes and intermediates useful in synthesis of nep inhibitors |
| CN105198775B (zh) | 2015-10-10 | 2017-11-14 | 凯瑞斯德生化(苏州)有限公司 | 一种手性N‑Boc联苯丙氨醇的制备方法 |
| JP7001597B2 (ja) | 2015-12-10 | 2022-01-19 | ノバルティス アーゲー | 新規なプロセスおよび中間体 |
| KR20170119447A (ko) | 2016-04-19 | 2017-10-27 | 주식회사 아미노로직스 | Dl-4,4'-바이페닐알라닌 알킬에스터로부터 d-4,4'-바이페닐알라닌 알킬에스터 또는 l-4,4'-바이페닐알라닌 알킬에스터를 제조하는 방법 |
| US20190256454A1 (en) | 2016-07-05 | 2019-08-22 | Novartis Ag | New process for early sacubitril intermediates |
| WO2018033866A1 (en) | 2016-08-17 | 2018-02-22 | Novartis Ag | New processes and intermediates for nep inhibitor synthesis |
| WO2018116203A1 (en) | 2016-12-23 | 2018-06-28 | Novartis Ag | New process for early sacubitril intermediates |
| JP6843696B2 (ja) * | 2017-04-28 | 2021-03-17 | キヤノン株式会社 | 電源装置及び画像形成装置 |
| UY38072A (es) | 2018-02-07 | 2019-10-01 | Novartis Ag | Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos |
| CN110183357B (zh) * | 2019-06-13 | 2021-09-24 | 甘肃皓天医药科技有限责任公司 | 一种用于制备沙库比曲中间体的制备方法 |
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| JPS61227555A (ja) | 1985-04-02 | 1986-10-09 | Mitsui Toatsu Chem Inc | Ｎ−アシルフエニルアラニン類の製造方法 |
| US5217996A (en) * | 1992-01-22 | 1993-06-08 | Ciba-Geigy Corporation | Biaryl substituted 4-amino-butyric acid amides |
| IL123986A (en) * | 1997-04-24 | 2011-10-31 | Organon Nv | Medicinal compounds |
| FR2833949B1 (fr) | 2001-12-21 | 2005-08-05 | Galderma Res & Dev | NOUVEAUX LIGANDS ACTIVATEURS DES RECEPTEURS PPARy, LEUR PROCEDE DE PREPARATION ET LEUR UTILISATION EN MEDECINE HUMAINE AINSI QU'EN COSMETIQUE |
| SI1467728T1 (sl) | 2002-01-17 | 2008-02-29 | Novartis Ag | Farmacevtski sestavki vkljucujoci valsartan in NEP inhibitorje |
| JP4270484B2 (ja) * | 2002-03-08 | 2009-06-03 | 第一ファインケミカル株式会社 | 光学活性フェニルアラニン誘導体の製造方法 |
| CN100336803C (zh) * | 2003-12-04 | 2007-09-12 | 上海药明康德新药开发有限公司 | 一种光学纯N－叔丁基氧羰基－β－二氟苯丙氨酸的制备方法 |
| GB0329584D0 (en) | 2003-12-20 | 2004-01-28 | Tanabe Seiyaku Co | Novel compounds |
| US7321055B2 (en) | 2005-08-04 | 2008-01-22 | Ajinomoto Co., Inc. | Production method of optically active dephenylalanine compounds |
| JP2007063267A (ja) * | 2005-08-04 | 2007-03-15 | Ajinomoto Co Inc | 光学活性なジフェニルアラニン化合物の製造方法 |
| CN101774941A (zh) * | 2009-01-13 | 2010-07-14 | 浙江九洲药业股份有限公司 | 2-酰基氨基-3-联苯基丙酸的制备及拆分方法 |
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| PL2387558T3 (pl) | 2015-03-31 |
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| US9181175B2 (en) | 2015-11-10 |
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| US20140179947A1 (en) | 2014-06-26 |
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| US8703990B2 (en) | 2014-04-22 |
| KR101699095B1 (ko) | 2017-01-23 |
| CN104557599A (zh) | 2015-04-29 |
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| EP2387558A4 (en) | 2012-08-08 |
| AU2010205973A1 (en) | 2011-08-04 |
| JP5687205B2 (ja) | 2015-03-18 |
| CN102482202A (zh) | 2012-05-30 |
| CN101774941A (zh) | 2010-07-14 |
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