NO874467L - Fremgangsmaate for fremstilling av 3-pyrrolidinoler. - Google Patents
Fremgangsmaate for fremstilling av 3-pyrrolidinoler.Info
- Publication number
- NO874467L NO874467L NO874467A NO874467A NO874467L NO 874467 L NO874467 L NO 874467L NO 874467 A NO874467 A NO 874467A NO 874467 A NO874467 A NO 874467A NO 874467 L NO874467 L NO 874467L
- Authority
- NO
- Norway
- Prior art keywords
- lower alkyl
- compound
- hydrogen
- formula
- phenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 42
- 238000002360 preparation method Methods 0.000 title claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- -1 pyrrolidinol compound Chemical class 0.000 claims description 49
- 150000001875 compounds Chemical class 0.000 claims description 47
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 42
- 239000002253 acid Substances 0.000 claims description 39
- 239000001257 hydrogen Substances 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 28
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 26
- 239000003054 catalyst Substances 0.000 claims description 25
- 239000007868 Raney catalyst Substances 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 15
- 230000003287 optical effect Effects 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 239000003929 acidic solution Substances 0.000 claims description 9
- 239000012458 free base Substances 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000006242 amine protecting group Chemical group 0.000 claims description 8
- CWLUFVAFWWNXJZ-UHFFFAOYSA-N 1-hydroxypyrrolidine Chemical compound ON1CCCC1 CWLUFVAFWWNXJZ-UHFFFAOYSA-N 0.000 claims description 7
- NPJZGNFGBMXLGQ-UHFFFAOYSA-N 3-hydroxy-4-(methylamino)butanenitrile Chemical compound CNCC(O)CC#N NPJZGNFGBMXLGQ-UHFFFAOYSA-N 0.000 claims description 7
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 7
- 238000010511 deprotection reaction Methods 0.000 claims description 7
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 230000002452 interceptive effect Effects 0.000 claims description 7
- 239000002585 base Substances 0.000 claims description 5
- 239000007810 chemical reaction solvent Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 claims description 4
- 239000002002 slurry Substances 0.000 claims description 4
- FLVFPAIGVBQGET-UHFFFAOYSA-N 1-methylpyrrolidin-3-ol Chemical compound CN1CCC(O)C1 FLVFPAIGVBQGET-UHFFFAOYSA-N 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 238000005292 vacuum distillation Methods 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims 2
- 239000004593 Epoxy Substances 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 11
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000005984 hydrogenation reaction Methods 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical class OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- AFSJSMGLWQBMPX-UHFFFAOYSA-N 4-amino-3-hydroxybutanenitrile Chemical compound NCC(O)CC#N AFSJSMGLWQBMPX-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 238000006476 reductive cyclization reaction Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 5
- HBRGVTLYZNPAFJ-UHFFFAOYSA-N 4-azido-3-hydroxybutanenitrile Chemical compound N#CCC(O)CN=[N+]=[N-] HBRGVTLYZNPAFJ-UHFFFAOYSA-N 0.000 description 4
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 4
- YQMXOIAIYXXXEE-UHFFFAOYSA-N 1-benzylpyrrolidin-3-ol Chemical compound C1C(O)CCN1CC1=CC=CC=C1 YQMXOIAIYXXXEE-UHFFFAOYSA-N 0.000 description 3
- XDLVSDROHPIIHF-UHFFFAOYSA-N 4-[benzyl(methyl)amino]-3-hydroxybutanenitrile Chemical compound N#CCC(O)CN(C)CC1=CC=CC=C1 XDLVSDROHPIIHF-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 239000013067 intermediate product Substances 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 150000002924 oxiranes Chemical class 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- ARXKVVRQIIOZGF-UHFFFAOYSA-N 1,2,4-butanetriol Chemical compound OCCC(O)CO ARXKVVRQIIOZGF-UHFFFAOYSA-N 0.000 description 2
- HXJHQHHJIQEZLD-UHFFFAOYSA-N 1,4-dimethylpyrrolidin-3-ol Chemical compound CC1CN(C)CC1O HXJHQHHJIQEZLD-UHFFFAOYSA-N 0.000 description 2
- IDBNECMSCRAUNU-UHFFFAOYSA-N 1-ethylpyrrolidin-3-ol Chemical compound CCN1CCC(O)C1 IDBNECMSCRAUNU-UHFFFAOYSA-N 0.000 description 2
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 2
- MHCQKHPTDGIEFT-UHFFFAOYSA-N 4-(ethylamino)-3-hydroxybutanenitrile Chemical compound CCNCC(O)CC#N MHCQKHPTDGIEFT-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000001743 benzylic group Chemical group 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 238000006264 debenzylation reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000002574 poison Substances 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- BRLQWZUYTZBJKN-GSVOUGTGSA-N (+)-Epichlorohydrin Chemical compound ClC[C@@H]1CO1 BRLQWZUYTZBJKN-GSVOUGTGSA-N 0.000 description 1
- MHRSSQGDFHPZPL-UHFFFAOYSA-N (3-cyano-2-hydroxypropyl) 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCC(O)CC#N)C=C1 MHRSSQGDFHPZPL-UHFFFAOYSA-N 0.000 description 1
- HBRGVTLYZNPAFJ-SCSAIBSYSA-N (3R)-4-azido-3-hydroxybutanenitrile Chemical compound N#CC[C@@H](O)CN=[N+]=[N-] HBRGVTLYZNPAFJ-SCSAIBSYSA-N 0.000 description 1
- FLVFPAIGVBQGET-RXMQYKEDSA-N (3r)-1-methylpyrrolidin-3-ol Chemical compound CN1CC[C@@H](O)C1 FLVFPAIGVBQGET-RXMQYKEDSA-N 0.000 description 1
- XDLVSDROHPIIHF-GFCCVEGCSA-N (3r)-4-[benzyl(methyl)amino]-3-hydroxybutanenitrile Chemical compound N#CC[C@@H](O)CN(C)CC1=CC=CC=C1 XDLVSDROHPIIHF-GFCCVEGCSA-N 0.000 description 1
- FLVFPAIGVBQGET-YFKPBYRVSA-N (3s)-1-methylpyrrolidin-3-ol Chemical compound CN1CC[C@H](O)C1 FLVFPAIGVBQGET-YFKPBYRVSA-N 0.000 description 1
- JHHZLHWJQPUNKB-BYPYZUCNSA-N (3s)-pyrrolidin-3-ol Chemical compound O[C@H]1CCNC1 JHHZLHWJQPUNKB-BYPYZUCNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- HYHQPNCVYMROQX-UHFFFAOYSA-N 1,2-dimethylpyrrolidin-3-ol Chemical compound CC1C(O)CCN1C HYHQPNCVYMROQX-UHFFFAOYSA-N 0.000 description 1
- LZCLRPYCYCEKBS-UHFFFAOYSA-N 1,3-dimethylpyrrolidin-3-ol Chemical compound CN1CCC(C)(O)C1 LZCLRPYCYCEKBS-UHFFFAOYSA-N 0.000 description 1
- PSSRAPMBSMSACN-UHFFFAOYSA-N 1,4-dibromobutan-2-ol Chemical compound BrCC(O)CCBr PSSRAPMBSMSACN-UHFFFAOYSA-N 0.000 description 1
- VCPKAWKGCQTPCR-UHFFFAOYSA-N 1-benzyl-3-hydroxypyrrolidine-2,5-dione Chemical compound O=C1C(O)CC(=O)N1CC1=CC=CC=C1 VCPKAWKGCQTPCR-UHFFFAOYSA-N 0.000 description 1
- LWCYKKRWFZZFMA-UHFFFAOYSA-N 1-hydroxy-3-methylpyrrolidine Chemical compound CC1CCN(O)C1 LWCYKKRWFZZFMA-UHFFFAOYSA-N 0.000 description 1
- MOBNLCPBAMKACS-UHFFFAOYSA-N 2-(1-chloroethyl)oxirane Chemical compound CC(Cl)C1CO1 MOBNLCPBAMKACS-UHFFFAOYSA-N 0.000 description 1
- VVHFXJOCUKBZFS-UHFFFAOYSA-N 2-(chloromethyl)-2-methyloxirane Chemical compound ClCC1(C)CO1 VVHFXJOCUKBZFS-UHFFFAOYSA-N 0.000 description 1
- MMTOSBCMFDNOIY-UHFFFAOYSA-N 2-(chloromethyl)-3-methyloxirane Chemical compound CC1OC1CCl MMTOSBCMFDNOIY-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MCFIDBIXPWJFER-UHFFFAOYSA-N 3-hydroxy-2-methyl-4-(methylamino)butanenitrile Chemical compound CNCC(O)C(C)C#N MCFIDBIXPWJFER-UHFFFAOYSA-N 0.000 description 1
- XLIDEAUKQVDNBH-UHFFFAOYSA-N 3-hydroxy-3-methyl-4-(methylamino)butanenitrile Chemical compound CNCC(C)(O)CC#N XLIDEAUKQVDNBH-UHFFFAOYSA-N 0.000 description 1
- HGHHUUMZJJCFLB-UHFFFAOYSA-N 3-hydroxy-4-(methylamino)butanenitrile;hydrochloride Chemical compound Cl.CNCC(O)CC#N HGHHUUMZJJCFLB-UHFFFAOYSA-N 0.000 description 1
- OKTHOHXKWKEPIF-UHFFFAOYSA-N 3-hydroxy-4-(n-methylanilino)butanenitrile Chemical compound N#CCC(O)CN(C)C1=CC=CC=C1 OKTHOHXKWKEPIF-UHFFFAOYSA-N 0.000 description 1
- YAUGXTMOISTUPX-UHFFFAOYSA-N 4-[benzyl(ethyl)amino]-3-hydroxybutanenitrile Chemical compound N#CCC(O)CN(CC)CC1=CC=CC=C1 YAUGXTMOISTUPX-UHFFFAOYSA-N 0.000 description 1
- MYIOODBUIKQFGN-UHFFFAOYSA-N 4-[benzyl(methyl)amino]-3-hydroxy-2-methylbutanenitrile Chemical compound N#CC(C)C(O)CN(C)CC1=CC=CC=C1 MYIOODBUIKQFGN-UHFFFAOYSA-N 0.000 description 1
- HQJQBIIYZAOYKT-UHFFFAOYSA-N 4-[benzyl(methyl)amino]-3-hydroxypentanenitrile Chemical compound N#CCC(O)C(C)N(C)CC1=CC=CC=C1 HQJQBIIYZAOYKT-UHFFFAOYSA-N 0.000 description 1
- LHBPNZDUNCZWFL-UHFFFAOYSA-N 4-chloro-3-hydroxybutanenitrile Chemical compound ClCC(O)CC#N LHBPNZDUNCZWFL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- YVZBCUPKAHWMOJ-RXMQYKEDSA-N [(2r)-3-cyano-2-hydroxypropyl] methanesulfonate Chemical compound CS(=O)(=O)OC[C@H](O)CC#N YVZBCUPKAHWMOJ-RXMQYKEDSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 230000003113 alkalizing effect Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000012351 deprotecting agent Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- SBPUJTNHAUBDKF-UHFFFAOYSA-N ethyl 2-(2-cyanoethylamino)acetate Chemical compound CCOC(=O)CNCCC#N SBPUJTNHAUBDKF-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- HVAAHUDGWQAAOJ-UHFFFAOYSA-N n-benzylethanamine Chemical compound CCNCC1=CC=CC=C1 HVAAHUDGWQAAOJ-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- NOQXXYIGRPAZJC-UHFFFAOYSA-N oxiran-2-ylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1OC1 NOQXXYIGRPAZJC-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 150000003673 urethanes Chemical class 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyrrole Compounds (AREA)
- Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US92354486A | 1986-10-27 | 1986-10-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO874467D0 NO874467D0 (no) | 1987-10-26 |
| NO874467L true NO874467L (no) | 1988-04-28 |
Family
ID=25448857
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO874467A NO874467L (no) | 1986-10-27 | 1987-10-26 | Fremgangsmaate for fremstilling av 3-pyrrolidinoler. |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0269258A3 (da) |
| JP (1) | JPS63122658A (da) |
| AU (1) | AU8015587A (da) |
| DK (1) | DK559387A (da) |
| FI (1) | FI874719A (da) |
| HU (2) | HU198009B (da) |
| IL (1) | IL83663A0 (da) |
| NO (1) | NO874467L (da) |
| PH (1) | PH23663A (da) |
| PT (1) | PT85993B (da) |
| ZA (1) | ZA876516B (da) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE62338B1 (en) * | 1988-06-22 | 1995-01-25 | Kanegafuchi Chemical Ind | Process for preparing 3-pyrrolidinol |
| JP2735326B2 (ja) * | 1989-12-02 | 1998-04-02 | 鐘淵化学工業株式会社 | ３‐ピロリジノールの製造法 |
| JPH0776209B2 (ja) * | 1990-04-11 | 1995-08-16 | 高砂香料工業株式会社 | 光学活性３―ヒドロキシピロリジン誘導体の製造方法 |
| DE4425071C2 (de) | 1994-07-15 | 1996-08-29 | Degussa | Verfahren zur Herstellung optisch aktiver Pyrrolidine mit hoher Enantiomerenreinheit |
| AU2003236065A1 (en) * | 2002-04-23 | 2003-11-10 | Kaneka Corporation | Process for producing 1-(lower alkyl)-3-hydroxypyrrolidine compound |
| JP2004244418A (ja) * | 2003-01-21 | 2004-09-02 | Toray Fine Chemicals Co Ltd | Ｎ−メチル含窒素環状アルコールの製造方法 |
| EP1926709A4 (en) * | 2005-08-25 | 2009-06-24 | Rstech Corp | PROCESS FOR THE SYNTHESIS OF A 3-HYDROXYPYRROLIDINE CHIRAL COMPOUND AND DERIVATIVES OF SAID HIGH OPTICAL PURITY COMPOUND |
| CA2744987C (en) | 2008-12-02 | 2018-01-16 | Chiralgen, Ltd. | Method for the synthesis of phosphorus atom modified nucleic acids |
| AU2010270714B2 (en) | 2009-07-06 | 2015-08-13 | Wave Life Sciences Ltd. | Novel nucleic acid prodrugs and methods use thereof |
| EP2620428B1 (en) | 2010-09-24 | 2019-05-22 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
| SG10201700554VA (en) | 2011-07-19 | 2017-03-30 | Wave Life Sciences Pte Ltd | Methods for the synthesis of functionalized nucleic acids |
| WO2014012081A2 (en) | 2012-07-13 | 2014-01-16 | Ontorii, Inc. | Chiral control |
| SG11201500239VA (en) | 2012-07-13 | 2015-03-30 | Wave Life Sciences Japan | Asymmetric auxiliary group |
| BR112015000723A2 (pt) | 2012-07-13 | 2017-06-27 | Shin Nippon Biomedical Laboratories Ltd | adjuvante de ácido nucléico quiral |
| EP3095461A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
| US10149905B2 (en) | 2014-01-15 | 2018-12-11 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having antitumor effect and antitumor agent |
| JPWO2015108046A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗アレルギー作用を有するキラル核酸アジュバンド及び抗アレルギー剤 |
| MX2016009290A (es) | 2014-01-16 | 2017-02-28 | Wave Life Sciences Ltd | Diseño quiral. |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2838521A (en) * | 1956-05-17 | 1958-06-10 | Robins Co Inc A H | Esters of amino alcohols |
| PT82077B (fr) * | 1985-02-26 | 1987-09-25 | Sanofi Sa | Procede pour l'obtention des derives aminoalcools peptidiques inhibiteurs de la renine et des proteases acides |
-
1987
- 1987-08-27 IL IL83663A patent/IL83663A0/xx unknown
- 1987-09-01 ZA ZA876516A patent/ZA876516B/xx unknown
- 1987-10-26 PH PH35981A patent/PH23663A/en unknown
- 1987-10-26 HU HU874395A patent/HU198009B/hu not_active IP Right Cessation
- 1987-10-26 PT PT85993A patent/PT85993B/pt not_active IP Right Cessation
- 1987-10-26 DK DK559387A patent/DK559387A/da not_active Application Discontinuation
- 1987-10-26 HU HU874768A patent/HU199413B/hu not_active IP Right Cessation
- 1987-10-26 NO NO874467A patent/NO874467L/no unknown
- 1987-10-27 EP EP87309475A patent/EP0269258A3/en not_active Withdrawn
- 1987-10-27 FI FI874719A patent/FI874719A/fi not_active IP Right Cessation
- 1987-10-27 AU AU80155/87A patent/AU8015587A/en not_active Abandoned
- 1987-10-27 JP JP62271594A patent/JPS63122658A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| FI874719A0 (fi) | 1987-10-27 |
| HU199413B (en) | 1990-02-28 |
| DK559387D0 (da) | 1987-10-26 |
| ZA876516B (en) | 1988-03-03 |
| EP0269258A2 (en) | 1988-06-01 |
| HUT47080A (en) | 1989-01-30 |
| IL83663A0 (en) | 1988-01-31 |
| EP0269258A3 (en) | 1989-11-15 |
| AU8015587A (en) | 1988-04-28 |
| PH23663A (en) | 1989-09-27 |
| NO874467D0 (no) | 1987-10-26 |
| HU198009B (en) | 1989-07-28 |
| HUT46304A (en) | 1988-10-28 |
| DK559387A (da) | 1988-04-28 |
| PT85993A (en) | 1987-11-01 |
| JPS63122658A (ja) | 1988-05-26 |
| PT85993B (pt) | 1990-08-31 |
| FI874719A (fi) | 1988-04-28 |
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