TW202317140A - 4-((r)-2-{[6-((s)-3-甲氧基-吡咯啶-1-基)-2-苯基-嘧啶-4-羰基]-胺基}-3-膦醯基-丙醯基)-哌-1-羧酸丁酯的合成方法 - Google Patents
4-((r)-2-{[6-((s)-3-甲氧基-吡咯啶-1-基)-2-苯基-嘧啶-4-羰基]-胺基}-3-膦醯基-丙醯基)-哌-1-羧酸丁酯的合成方法 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 146
- 230000015572 biosynthetic process Effects 0.000 title abstract description 15
- 238000003786 synthesis reaction Methods 0.000 title abstract description 15
- FYXHWMQPCJOJCH-GMAHTHKFSA-N selatogrel Chemical compound C1CN(C(=O)OCCCC)CCN1C(=O)[C@H](CP(O)(O)=O)NC(=O)C1=CC(N2C[C@H](CC2)OC)=NC(C=2C=CC=CC=2)=N1 FYXHWMQPCJOJCH-GMAHTHKFSA-N 0.000 title abstract description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 214
- 150000001875 compounds Chemical class 0.000 claims description 203
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 138
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 138
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 137
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 94
- 239000000203 mixture Substances 0.000 claims description 73
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- 238000006243 chemical reaction Methods 0.000 claims description 48
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- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 239000003960 organic solvent Substances 0.000 claims description 31
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 24
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 claims description 23
- 238000011065 in-situ storage Methods 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 239000012038 nucleophile Substances 0.000 claims description 21
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
- -1 hydrochloride Compound Chemical class 0.000 claims description 10
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 47
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- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
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- 235000019260 propionic acid Nutrition 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
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- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 4
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
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- 239000003153 chemical reaction reagent Substances 0.000 description 4
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
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- 238000002360 preparation method Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- SJSCDCIOCOARJQ-YDALLXLXSA-M sodium 6-[(3S)-3-methoxypyrrolidin-1-yl]-2-phenylpyrimidine-4-carboxylate Chemical compound CO[C@@H]1CN(CC1)C1=CC(=NC(=N1)C1=CC=CC=C1)C(=O)[O-].[Na+] SJSCDCIOCOARJQ-YDALLXLXSA-M 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
- BDFAOUQQXJIZDG-UHFFFAOYSA-N 2-methylpropane-1-thiol Chemical compound CC(C)CS BDFAOUQQXJIZDG-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
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- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
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- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- AUYBSFAHQLKXSW-UHFFFAOYSA-N 1,2-dichloroethane;3-(ethyliminomethylideneamino)-n,n-dimethylpropan-1-amine;hydrochloride Chemical compound Cl.ClCCCl.CCN=C=NCCCN(C)C AUYBSFAHQLKXSW-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- DXDJODNRRDUGCN-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2lambda5,4lambda5,6lambda5-trioxatriphosphonane 2,4,6-trioxide Chemical compound C(CC)P1(OCCCP(OP(O1)(CCC)=O)(CCC)=O)=O DXDJODNRRDUGCN-UHFFFAOYSA-N 0.000 description 1
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- 238000004364 calculation method Methods 0.000 description 1
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- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
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- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
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- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940121495 selatogrel Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WMXCDAVJEZZYLT-UHFFFAOYSA-N tert-butylthiol Chemical compound CC(C)(C)S WMXCDAVJEZZYLT-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
-
- 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
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP2021069486 | 2021-07-13 | ||
| WOPCT/EP2021/069486 | 2021-07-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202317140A true TW202317140A (zh) | 2023-05-01 |
Family
ID=82748669
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW111126010A TW202317140A (zh) | 2021-07-13 | 2022-07-12 | 4-((r)-2-{[6-((s)-3-甲氧基-吡咯啶-1-基)-2-苯基-嘧啶-4-羰基]-胺基}-3-膦醯基-丙醯基)-哌-1-羧酸丁酯的合成方法 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20240317784A1 (https=) |
| EP (1) | EP4370525A2 (https=) |
| JP (1) | JP2024524658A (https=) |
| KR (1) | KR20240033005A (https=) |
| CN (1) | CN117616033A (https=) |
| CA (1) | CA3223733A1 (https=) |
| IL (1) | IL309948A (https=) |
| MX (1) | MX2024000653A (https=) |
| TW (1) | TW202317140A (https=) |
| WO (1) | WO2023285342A2 (https=) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2225253B1 (en) * | 2007-11-29 | 2012-06-27 | Actelion Pharmaceuticals Ltd. | Phosphonic acid derivates and their use as p2y12 receptor antagonists |
| EP3515924B1 (en) * | 2016-09-22 | 2021-12-15 | Idorsia Pharmaceuticals Ltd | Crystalline forms |
| MA49887A (fr) | 2017-03-15 | 2020-06-24 | Idorsia Pharmaceuticals Ltd | Administration sous-cutanée d'un antagoniste du récepteur p2y12 |
-
2022
- 2022-07-11 MX MX2024000653A patent/MX2024000653A/es unknown
- 2022-07-11 JP JP2024501708A patent/JP2024524658A/ja active Pending
- 2022-07-11 US US18/579,110 patent/US20240317784A1/en active Pending
- 2022-07-11 KR KR1020247004672A patent/KR20240033005A/ko active Pending
- 2022-07-11 WO PCT/EP2022/069238 patent/WO2023285342A2/en not_active Ceased
- 2022-07-11 EP EP22748321.1A patent/EP4370525A2/en active Pending
- 2022-07-11 CA CA3223733A patent/CA3223733A1/en active Pending
- 2022-07-11 CN CN202280048853.5A patent/CN117616033A/zh active Pending
- 2022-07-11 IL IL309948A patent/IL309948A/en unknown
- 2022-07-12 TW TW111126010A patent/TW202317140A/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2024524658A (ja) | 2024-07-05 |
| KR20240033005A (ko) | 2024-03-12 |
| IL309948A (en) | 2024-03-01 |
| WO2023285342A3 (en) | 2023-04-13 |
| WO2023285342A2 (en) | 2023-01-19 |
| CN117616033A (zh) | 2024-02-27 |
| CA3223733A1 (en) | 2023-01-19 |
| EP4370525A2 (en) | 2024-05-22 |
| US20240317784A1 (en) | 2024-09-26 |
| MX2024000653A (es) | 2024-01-31 |
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