NZ524159A - Gem-substituted alpha v beta 3 integrin antagonists - Google Patents

Info

Publication number

NZ524159A

NZ524159A NZ524159A NZ52415901A NZ524159A NZ 524159 A NZ524159 A NZ 524159A NZ 524159 A NZ524159 A NZ 524159A NZ 52415901 A NZ52415901 A NZ 52415901A NZ 524159 A NZ524159 A NZ 524159A

Authority

NZ

New Zealand

Prior art keywords

group

phenyl

solution

product

alkyl

Prior art date

2000-08-30

Links

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• Global Dossier
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• 239000005557 antagonist Substances 0.000 title claims description 22
• 102000008607 Integrin beta3 Human genes 0.000 title description 2
• 108010020950 Integrin beta3 Proteins 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 146
• 108010044426 integrins Proteins 0.000 claims abstract description 37
• 102000006495 integrins Human genes 0.000 claims abstract description 37
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 33
• 239000003814 drug Substances 0.000 claims abstract description 18
• 230000004614 tumor growth Effects 0.000 claims abstract description 14
• 206010027476 Metastases Diseases 0.000 claims abstract description 13
• 230000033115 angiogenesis Effects 0.000 claims abstract description 13
• 230000009401 metastasis Effects 0.000 claims abstract description 12
• 208000001132 Osteoporosis Diseases 0.000 claims abstract description 11
• 208000002780 macular degeneration Diseases 0.000 claims abstract description 11
• 238000004519 manufacturing process Methods 0.000 claims abstract description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
• 208000037803 restenosis Diseases 0.000 claims abstract description 10
• 208000017442 Retinal disease Diseases 0.000 claims abstract description 9
• 206010038923 Retinopathy Diseases 0.000 claims abstract description 9
• 206010003246 arthritis Diseases 0.000 claims abstract description 9
• 230000015590 smooth muscle cell migration Effects 0.000 claims abstract description 9
• 208000008750 humoral hypercalcemia of malignancy Diseases 0.000 claims abstract description 8
• 230000001404 mediated effect Effects 0.000 claims abstract description 6
• 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 86
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 69
• -1 polyethylene Polymers 0.000 claims description 68
• 125000003118 aryl group Chemical group 0.000 claims description 57
• 125000003545 alkoxy group Chemical group 0.000 claims description 44
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 41
• 125000001072 heteroaryl group Chemical group 0.000 claims description 40
• 229910052717 sulfur Inorganic materials 0.000 claims description 40
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 37
• 125000001188 haloalkyl group Chemical group 0.000 claims description 35
• 238000000034 method Methods 0.000 claims description 34
• 229910052760 oxygen Inorganic materials 0.000 claims description 34
• 229910052757 nitrogen Inorganic materials 0.000 claims description 33
• 239000007787 solid Substances 0.000 claims description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims description 29
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 25
• 229920006395 saturated elastomer Polymers 0.000 claims description 25
• 239000002253 acid Substances 0.000 claims description 22
• 125000000304 alkynyl group Chemical group 0.000 claims description 21
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 21
• 229910052736 halogen Inorganic materials 0.000 claims description 21
• 150000002367 halogens Chemical class 0.000 claims description 21
• 125000003342 alkenyl group Chemical group 0.000 claims description 20
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
• 125000002252 acyl group Chemical group 0.000 claims description 18
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
• 125000002950 monocyclic group Chemical group 0.000 claims description 18
• 150000003839 salts Chemical class 0.000 claims description 18
• 125000005842 heteroatom Chemical group 0.000 claims description 17
• 125000003282 alkyl amino group Chemical group 0.000 claims description 16
• 238000003556 assay Methods 0.000 claims description 16
• 125000004001 thioalkyl group Chemical group 0.000 claims description 15
• 150000003457 sulfones Chemical class 0.000 claims description 14
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
• 230000005764 inhibitory process Effects 0.000 claims description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
• 125000001424 substituent group Chemical group 0.000 claims description 13
• 229940124530 sulfonamide Drugs 0.000 claims description 13
• 150000003456 sulfonamides Chemical class 0.000 claims description 13
• 125000002619 bicyclic group Chemical group 0.000 claims description 12
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
• RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 12
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 11
• 125000004442 acylamino group Chemical group 0.000 claims description 11
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
• 229910052799 carbon Inorganic materials 0.000 claims description 11
• 125000000623 heterocyclic group Chemical group 0.000 claims description 11
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
• 239000001257 hydrogen Substances 0.000 claims description 10
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 10
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 9
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 9
• 230000009826 neoplastic cell growth Effects 0.000 claims description 9
• YVHAIVPPUIZFBA-UHFFFAOYSA-N Cyclopentylacetic acid Chemical compound OC(=O)CC1CCCC1 YVHAIVPPUIZFBA-UHFFFAOYSA-N 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 8
• 238000012360 testing method Methods 0.000 claims description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
• 241000282414 Homo sapiens Species 0.000 claims description 7
• 150000001336 alkenes Chemical group 0.000 claims description 7
• 150000001345 alkine derivatives Chemical class 0.000 claims description 7
• 125000001769 aryl amino group Chemical group 0.000 claims description 7
• 210000004369 blood Anatomy 0.000 claims description 7
• 239000008280 blood Substances 0.000 claims description 7
• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 7
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 6
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 6
• 150000003857 carboxamides Chemical class 0.000 claims description 6
• 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 6
• 125000004122 cyclic group Chemical group 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 5
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
• 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 5
• 125000003368 amide group Chemical group 0.000 claims description 5
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 5
• 125000004104 aryloxy group Chemical group 0.000 claims description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 125000005518 carboxamido group Chemical group 0.000 claims description 5
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
• 125000004993 haloalkoxycarbonyl group Chemical group 0.000 claims description 5
• 125000004692 haloalkylcarbonyl group Chemical group 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• WJSYFMVFTAGCMV-UHFFFAOYSA-N 3-methyl-3-[[4-[3-(pyridin-2-ylamino)propoxy]phenyl]methyl]pent-4-enoic acid Chemical compound C1=CC(CC(CC(O)=O)(C)C=C)=CC=C1OCCCNC1=CC=CC=N1 WJSYFMVFTAGCMV-UHFFFAOYSA-N 0.000 claims description 4
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000000524 functional group Chemical group 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 4
• 210000002381 plasma Anatomy 0.000 claims description 4
• 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 4
• ZCZVGQCBSJLDDS-UHFFFAOYSA-N 1,2,3,4-tetrahydro-1,8-naphthyridine Chemical compound C1=CC=C2CCCNC2=N1 ZCZVGQCBSJLDDS-UHFFFAOYSA-N 0.000 claims description 3
• LZYZWYOPJANCRQ-UHFFFAOYSA-N 2-[1-[2-oxo-2-[4-[2-(pyridin-2-ylamino)ethoxy]phenyl]ethyl]cyclopentyl]acetic acid Chemical compound C=1C=C(OCCNC=2N=CC=CC=2)C=CC=1C(=O)CC1(CC(=O)O)CCCC1 LZYZWYOPJANCRQ-UHFFFAOYSA-N 0.000 claims description 3
• KVVDRQDTODKIJD-UHFFFAOYSA-N 2-cyclopropylacetic acid Chemical compound OC(=O)CC1CC1 KVVDRQDTODKIJD-UHFFFAOYSA-N 0.000 claims description 3
• 229930194542 Keto Natural products 0.000 claims description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
• 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 3
• 125000005038 alkynylalkyl group Chemical group 0.000 claims description 3
• 125000001246 bromo group Chemical group Br* 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 229910001873 dinitrogen Inorganic materials 0.000 claims description 3
• 230000009977 dual effect Effects 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 150000002431 hydrogen Chemical class 0.000 claims description 3
• 125000000468 ketone group Chemical group 0.000 claims description 3
• 150000002596 lactones Chemical class 0.000 claims description 3
• 238000002156 mixing Methods 0.000 claims description 3
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 3
• 150000003568 thioethers Chemical group 0.000 claims description 3
• XYNHCZVSWZBUJW-UHFFFAOYSA-N 2-[1-[[4-[3-(pyridin-2-ylamino)propoxy]phenyl]methyl]cyclobutyl]acetic acid Chemical compound C=1C=C(OCCCNC=2N=CC=CC=2)C=CC=1CC1(CC(=O)O)CCC1 XYNHCZVSWZBUJW-UHFFFAOYSA-N 0.000 claims description 2
• RMKCCAWNOBHOKM-UHFFFAOYSA-N 2-[1-acetyl-3-[[4-[3-(pyridin-2-ylamino)propoxy]phenyl]methyl]piperidin-3-yl]acetic acid Chemical compound C1N(C(=O)C)CCCC1(CC(O)=O)CC(C=C1)=CC=C1OCCCNC1=CC=CC=N1 RMKCCAWNOBHOKM-UHFFFAOYSA-N 0.000 claims description 2
• KGMWOJCHZPZNQZ-UHFFFAOYSA-N 3,3-dimethyl-4-[4-[3-(pyridin-2-ylamino)propoxy]phenyl]butanoic acid Chemical compound C1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 KGMWOJCHZPZNQZ-UHFFFAOYSA-N 0.000 claims description 2
• QGIRZMVNVDLIKQ-UHFFFAOYSA-N 3-benzyl-3-methyl-4-[4-[3-(pyridin-2-ylamino)propoxy]phenyl]butanoic acid Chemical compound C=1C=C(OCCCNC=2N=CC=CC=2)C=CC=1CC(CC(O)=O)(C)CC1=CC=CC=C1 QGIRZMVNVDLIKQ-UHFFFAOYSA-N 0.000 claims description 2
• SAJQLKDAKITQMK-UHFFFAOYSA-N 4-N-(1,3-oxazol-2-yl)-2-N-pyrimidin-2-yl-3-N-(1,3-thiazol-2-yl)quinoline-2,3,4-triamine Chemical compound N=1C=CSC=1NC=1C(NC=2N=CC=CN=2)=NC2=CC=CC=C2C=1NC1=NC=CO1 SAJQLKDAKITQMK-UHFFFAOYSA-N 0.000 claims description 2
• VITTYGWUOFXKLZ-UHFFFAOYSA-N 4-[2-bromo-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound C1=C(Br)C(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 VITTYGWUOFXKLZ-UHFFFAOYSA-N 0.000 claims description 2
• HCWTVUOVODBGBH-UHFFFAOYSA-N 4-[2-ethynyl-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound C1=C(C#C)C(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 HCWTVUOVODBGBH-UHFFFAOYSA-N 0.000 claims description 2
• IZDGOARRQXXAQG-UHFFFAOYSA-N 4-[3-chloro-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound ClC1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 IZDGOARRQXXAQG-UHFFFAOYSA-N 0.000 claims description 2
• UOACMCWVCLVCAD-UHFFFAOYSA-N 4-[3-fluoro-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound FC1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 UOACMCWVCLVCAD-UHFFFAOYSA-N 0.000 claims description 2
• KMERJFNZURFHFM-UHFFFAOYSA-N 4-[3-methoxy-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound COC1=CC(CC(C)(C)CC(O)=O)=CC=C1OCCCNC1=CC=CC=N1 KMERJFNZURFHFM-UHFFFAOYSA-N 0.000 claims description 2
• 239000005711 Benzoic acid Substances 0.000 claims description 2
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
• GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 claims description 2
• 125000006524 alkoxy alkyl amino group Chemical group 0.000 claims description 2
• 150000003973 alkyl amines Chemical class 0.000 claims description 2
• 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 2
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 2
• 125000005265 dialkylamine group Chemical group 0.000 claims description 2
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 2
• SBOJXQVPLKSXOG-UHFFFAOYSA-N o-amino-hydroxylamine Chemical group NON SBOJXQVPLKSXOG-UHFFFAOYSA-N 0.000 claims description 2
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Chemical group CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 2
• 239000013641 positive control Substances 0.000 claims description 2
• LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 2
• 230000004044 response Effects 0.000 claims description 2
• 239000011780 sodium chloride Substances 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 21
• 210000004623 platelet-rich plasma Anatomy 0.000 claims 4
• 239000004698 Polyethylene Substances 0.000 claims 2
• 238000004220 aggregation Methods 0.000 claims 2
• 230000002776 aggregation Effects 0.000 claims 2
• 231100000673 dose–response relationship Toxicity 0.000 claims 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims 2
• 229920000573 polyethylene Polymers 0.000 claims 2
• ZYDMKCSBAHXNSP-UHFFFAOYSA-N 2-[1-[2-oxo-2-[4-[3-(pyridin-2-ylamino)propoxy]phenyl]ethyl]cyclopentyl]acetic acid Chemical compound C=1C=C(OCCCNC=2N=CC=CC=2)C=CC=1C(=O)CC1(CC(=O)O)CCCC1 ZYDMKCSBAHXNSP-UHFFFAOYSA-N 0.000 claims 1
• NUWKCAMXYJOTPQ-UHFFFAOYSA-N 4-[3-bromo-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound BrC1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 NUWKCAMXYJOTPQ-UHFFFAOYSA-N 0.000 claims 1
• FUYKZCRCKXFKSE-UHFFFAOYSA-N 4-[3-bromo-5-fluoro-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound BrC1=CC(CC(C)(CC(O)=O)C)=CC(F)=C1OCCCNC1=CC=CC=N1 FUYKZCRCKXFKSE-UHFFFAOYSA-N 0.000 claims 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims 1
• 229960001138 acetylsalicylic acid Drugs 0.000 claims 1
• 238000005119 centrifugation Methods 0.000 claims 1
• 238000010790 dilution Methods 0.000 claims 1
• 239000012895 dilution Substances 0.000 claims 1
• 125000004992 haloalkylamino group Chemical group 0.000 claims 1
• 238000003306 harvesting Methods 0.000 claims 1
• 125000004585 polycyclic heterocycle group Chemical group 0.000 claims 1
• 239000013049 sediment Substances 0.000 claims 1
• 239000001509 sodium citrate Substances 0.000 claims 1
• HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims 1
• 229940038773 trisodium citrate Drugs 0.000 claims 1
• 239000003643 water by type Substances 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 481
• 239000000047 product Substances 0.000 description 277
• 239000000243 solution Substances 0.000 description 274
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 247
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 228
• 235000019439 ethyl acetate Nutrition 0.000 description 168
• 238000006243 chemical reaction Methods 0.000 description 156
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 153
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 146
• 229940093499 ethyl acetate Drugs 0.000 description 144
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 142
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 123
• 239000000203 mixture Substances 0.000 description 123
• 229910001868 water Inorganic materials 0.000 description 123
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 117
• 239000003921 oil Substances 0.000 description 91
• 235000019198 oils Nutrition 0.000 description 91
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 86
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
• 239000000741 silica gel Substances 0.000 description 74
• 229910002027 silica gel Inorganic materials 0.000 description 74
• 150000003254 radicals Chemical class 0.000 description 66
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 61
• 238000004587 chromatography analysis Methods 0.000 description 60
• 239000011541 reaction mixture Substances 0.000 description 58
• 239000012267 brine Substances 0.000 description 53
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 53
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 50
• 235000019441 ethanol Nutrition 0.000 description 49
• 238000005160 1H NMR spectroscopy Methods 0.000 description 47
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 47
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 46
• 239000002904 solvent Substances 0.000 description 45
• KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 43
• 239000012044 organic layer Substances 0.000 description 41
• 239000010410 layer Substances 0.000 description 40
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 38
• 239000000706 filtrate Substances 0.000 description 37
• 239000012043 crude product Substances 0.000 description 34
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 34
• ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
• 230000002829 reductive effect Effects 0.000 description 32
• 239000000284 extract Substances 0.000 description 31
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 31
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