TWI483926B - 掌性催化劑及其鹽之製造方法 - Google Patents
掌性催化劑及其鹽之製造方法 Download PDFInfo
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- TWI483926B TWI483926B TW101145127A TW101145127A TWI483926B TW I483926 B TWI483926 B TW I483926B TW 101145127 A TW101145127 A TW 101145127A TW 101145127 A TW101145127 A TW 101145127A TW I483926 B TWI483926 B TW I483926B
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- Prior art keywords
- compound
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- group
- benzyl
- enantiomers
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- 238000000034 method Methods 0.000 title claims description 58
- 150000003839 salts Chemical class 0.000 title claims description 39
- 239000003054 catalyst Substances 0.000 title description 36
- 230000008569 process Effects 0.000 title description 17
- 238000004519 manufacturing process Methods 0.000 title description 13
- 150000001875 compounds Chemical class 0.000 claims description 144
- -1 disulfide compound Chemical class 0.000 claims description 63
- 238000006243 chemical reaction Methods 0.000 claims description 53
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 39
- 229940124530 sulfonamide Drugs 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 150000003456 sulfonamides Chemical class 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 27
- 239000003638 chemical reducing agent Substances 0.000 claims description 26
- 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 24
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 150000003573 thiols Chemical class 0.000 claims description 19
- 229910052751 metal Inorganic materials 0.000 claims description 17
- 239000002184 metal Substances 0.000 claims description 17
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 14
- 150000007513 acids Chemical class 0.000 claims description 13
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 150000003460 sulfonic acids Chemical class 0.000 claims description 9
- 150000001735 carboxylic acids Chemical class 0.000 claims description 8
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 8
- 239000011707 mineral Substances 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 238000011914 asymmetric synthesis Methods 0.000 claims description 7
- 229910052987 metal hydride Inorganic materials 0.000 claims description 6
- 150000004681 metal hydrides Chemical class 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 239000000376 reactant Substances 0.000 claims description 6
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical group [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 claims description 5
- 238000007294 asymmetric addition reaction Methods 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical group [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 claims description 3
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 2
- 229910001092 metal group alloy Inorganic materials 0.000 claims description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 40
- 239000000243 solution Substances 0.000 description 40
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 31
- 239000000203 mixture Substances 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
- 230000015572 biosynthetic process Effects 0.000 description 28
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical class SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 27
- 239000000047 product Substances 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- 238000003786 synthesis reaction Methods 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- 150000003840 hydrochlorides Chemical class 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- 150000002019 disulfides Chemical class 0.000 description 14
- 239000007787 solid Substances 0.000 description 13
- 239000010410 layer Substances 0.000 description 12
- LSDPWZHWYPCBBB-UHFFFAOYSA-N methyl mercaptane Natural products SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 238000006722 reduction reaction Methods 0.000 description 12
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 11
- 150000002081 enamines Chemical class 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 10
- 239000003446 ligand Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 238000007259 addition reaction Methods 0.000 description 9
- 238000005755 formation reaction Methods 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000011701 zinc Substances 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 238000006555 catalytic reaction Methods 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 229910052725 zinc Inorganic materials 0.000 description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 150000001728 carbonyl compounds Chemical class 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- RXWAXIDATPTAOS-YRGRVCCFSA-N [(1r,3r,4s)-7,7-dimethyl-3-morpholin-4-yl-4-bicyclo[2.2.1]heptanyl]methanethiol Chemical compound N1([C@H]2[C@@]3(CC[C@](C2)(C3(C)C)[H])CS)CCOCC1 RXWAXIDATPTAOS-YRGRVCCFSA-N 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- AUVQSFSCHVUYTC-CTMQZQKCSA-N (s)-[(1r)-7,7-dimethyl-3-morpholin-4-yl-4-bicyclo[2.2.1]heptanyl]-morpholin-4-ylmethanesulfonamide Chemical compound N1([C@H](C23CC[C@](CC3N3CCOCC3)(C2(C)C)[H])S(N)(=O)=O)CCOCC1 AUVQSFSCHVUYTC-CTMQZQKCSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 235000010755 mineral Nutrition 0.000 description 5
- 150000002894 organic compounds Chemical class 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- LFQVGNAGJXFDGR-VVXOQCHWSA-N N1C(=CC2=CC=CC=C12)N.C(C1=CC=CC=C1)N[C@H]1[C@]2(CC[C@H](C1)C2(C)C)C Chemical compound N1C(=CC2=CC=CC=C12)N.C(C1=CC=CC=C1)N[C@H]1[C@]2(CC[C@H](C1)C2(C)C)C LFQVGNAGJXFDGR-VVXOQCHWSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- 125000003367 polycyclic group Chemical group 0.000 description 4
- 229920001296 polysiloxane Polymers 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- DYUQAZSOFZSPHD-SECBINFHSA-N (1r)-1-phenylpropan-1-ol Chemical compound CC[C@@H](O)C1=CC=CC=C1 DYUQAZSOFZSPHD-SECBINFHSA-N 0.000 description 3
- 238000011925 1,2-addition Methods 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- IGDZKSSYCRMBJW-RJYMGMSLSA-N 4-[(1r,3r,4s)-4-[[(7,7-dimethyl-3-morpholin-4-yl-4-bicyclo[2.2.1]heptanyl)methyldisulfanyl]methyl]-7,7-dimethyl-3-bicyclo[2.2.1]heptanyl]morpholine Chemical compound C([C@@]12CC[C@](C[C@H]2N2CCOCC2)(C1(C)C)[H])SSCC1(C2(C)C)CCC2CC1N1CCOCC1 IGDZKSSYCRMBJW-RJYMGMSLSA-N 0.000 description 3
- 239000005909 Kieselgur Substances 0.000 description 3
- 229910010082 LiAlH Inorganic materials 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000011097 chromatography purification Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- ZUBZATZOEPUUQF-UHFFFAOYSA-N isopropylhexane Natural products CCCCCCC(C)C ZUBZATZOEPUUQF-UHFFFAOYSA-N 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 238000004305 normal phase HPLC Methods 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- ABOYDMHGKWRPFD-UHFFFAOYSA-N phenylmethanesulfonamide Chemical class NS(=O)(=O)CC1=CC=CC=C1 ABOYDMHGKWRPFD-UHFFFAOYSA-N 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 125000006413 ring segment Chemical group 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000000707 stereoselective effect Effects 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 3
- DUGVPFYWJVLYJY-BFYDXBDKSA-N 1-[(1r,3r,4s)-3-amino-7,7-dimethyl-4-bicyclo[2.2.1]heptanyl]-n-benzylmethanesulfonamide Chemical compound C([C@@]12CC[C@](C[C@H]2N)(C1(C)C)[H])S(=O)(=O)NCC1=CC=CC=C1 DUGVPFYWJVLYJY-BFYDXBDKSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- HQPJVYTYFKOCHO-UHFFFAOYSA-N CC1(C2(C(=CC1CC2)N2CCOCC2)CS(=O)(=O)N)C Chemical compound CC1(C2(C(=CC1CC2)N2CCOCC2)CS(=O)(=O)N)C HQPJVYTYFKOCHO-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- LUFPJJNWMYZRQE-UHFFFAOYSA-N benzylsulfanylmethylbenzene Chemical compound C=1C=CC=CC=1CSCC1=CC=CC=C1 LUFPJJNWMYZRQE-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 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 2
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 230000000779 depleting effect Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 229940071870 hydroiodic acid Drugs 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 150000002484 inorganic compounds Chemical class 0.000 description 2
- 229910010272 inorganic material Inorganic materials 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
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- ULEWNLVMPPCOGC-SFHLNBCPSA-N n-benzyl-1-[(1r,3r,4s)-7,7-dimethyl-3-morpholin-4-yl-4-bicyclo[2.2.1]heptanyl]methanesulfonamide Chemical compound C([C@@]12CC[C@](C[C@H]2N2CCOCC2)(C1(C)C)[H])S(=O)(=O)NCC1=CC=CC=C1 ULEWNLVMPPCOGC-SFHLNBCPSA-N 0.000 description 2
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- FTIMWVSQXCWTAW-UHFFFAOYSA-N ruthenium Chemical compound [Ru].[Ru] FTIMWVSQXCWTAW-UHFFFAOYSA-N 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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- 150000003455 sulfinic acids Chemical class 0.000 description 1
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- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
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- XDLNRRRJZOJTRW-UHFFFAOYSA-N thiohypochlorous acid Chemical compound ClS XDLNRRRJZOJTRW-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
-
- 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
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161565449P | 2011-11-30 | 2011-11-30 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201335127A TW201335127A (zh) | 2013-09-01 |
| TWI483926B true TWI483926B (zh) | 2015-05-11 |
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| Application Number | Title | Priority Date | Filing Date |
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| TW101145127A TWI483926B (zh) | 2011-11-30 | 2012-11-30 | 掌性催化劑及其鹽之製造方法 |
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|---|---|
| US (1) | US8859765B2 (https=) |
| EP (1) | EP2785688B1 (https=) |
| JP (1) | JP5918386B2 (https=) |
| KR (1) | KR101647415B1 (https=) |
| CN (1) | CN103974932B (https=) |
| AU (1) | AU2012346860B2 (https=) |
| BR (1) | BR112014013285A8 (https=) |
| CA (1) | CA2855751C (https=) |
| IL (1) | IL232574A (https=) |
| TW (1) | TWI483926B (https=) |
| WO (1) | WO2013080049A2 (https=) |
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| JP6261111B2 (ja) * | 2013-07-17 | 2018-01-17 | 国立大学法人名古屋大学 | アレーンスルホンアミドの還元方法及びアレーンスルホン酸の製法 |
| KR20160000989U (ko) | 2014-09-18 | 2016-03-28 | 엘에스산전 주식회사 | 전기 커넥터 |
| CN114436911B (zh) * | 2022-03-17 | 2023-04-28 | 南京林业大学 | 一种樟脑磺酰苄胺类化合物的制备方法及其应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110269955A1 (en) * | 2010-04-30 | 2011-11-03 | Uang Biin-Jiun | Method for preparing 2-morpholinoisobornane- 10-thiol and intermediates formed therein |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8168835B2 (en) * | 2010-05-26 | 2012-05-01 | National Tsing Hua University | Method for preparing propargylic alcohol catalyzed by 2-morpholinoisobornane-10-thiol |
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2012
- 2012-11-29 WO PCT/IB2012/002910 patent/WO2013080049A2/en not_active Ceased
- 2012-11-29 KR KR1020147017924A patent/KR101647415B1/ko not_active Expired - Fee Related
- 2012-11-29 CA CA2855751A patent/CA2855751C/en not_active Expired - Fee Related
- 2012-11-29 AU AU2012346860A patent/AU2012346860B2/en not_active Ceased
- 2012-11-29 EP EP12853125.8A patent/EP2785688B1/en active Active
- 2012-11-29 BR BR112014013285A patent/BR112014013285A8/pt not_active IP Right Cessation
- 2012-11-29 JP JP2014543996A patent/JP5918386B2/ja not_active Expired - Fee Related
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- 2012-11-29 CN CN201280059398.5A patent/CN103974932B/zh not_active Expired - Fee Related
- 2012-11-30 TW TW101145127A patent/TWI483926B/zh not_active IP Right Cessation
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110269955A1 (en) * | 2010-04-30 | 2011-11-03 | Uang Biin-Jiun | Method for preparing 2-morpholinoisobornane- 10-thiol and intermediates formed therein |
Non-Patent Citations (3)
| Title |
|---|
| WU, H.-L. ET AL.: 'Asymmetric addition of dimethylzinc to alpha-ketoesters catalyzed by (-)-MITH' JOURNAL OF ORGANIC CHEMISTRY vol. 73, no. 16, 2008, pages 6445 - 6447 * |
| WU, P.-Y. ET AL.: 'Asymmetric synthesis of functionalized diarylmethanols catalyzed by a new gamma-amino thiol' JOURNAL OF ORGANIC CHEMISTRY vol. 71, 2006, pages 833 - 835 * |
| WU, P.-Y. ET AL.: 'Asymmetric synthesis of propargylic alcohols catalyzed by (-)-MITH' TETRAHEDRON: ASYMMETRY vol. 20, 2009, pages 1837 - 1841 * |
Also Published As
| Publication number | Publication date |
|---|---|
| BR112014013285A2 (pt) | 2017-06-13 |
| CA2855751C (en) | 2017-02-21 |
| EP2785688A4 (en) | 2015-07-15 |
| WO2013080049A3 (en) | 2013-08-08 |
| WO2013080049A2 (en) | 2013-06-06 |
| EP2785688A2 (en) | 2014-10-08 |
| US20130150574A1 (en) | 2013-06-13 |
| IL232574A (en) | 2017-02-28 |
| JP2015505827A (ja) | 2015-02-26 |
| EP2785688B1 (en) | 2017-09-13 |
| BR112014013285A8 (pt) | 2017-06-20 |
| KR101647415B1 (ko) | 2016-08-10 |
| CA2855751A1 (en) | 2013-06-06 |
| JP5918386B2 (ja) | 2016-05-18 |
| KR20140097517A (ko) | 2014-08-06 |
| CN103974932A (zh) | 2014-08-06 |
| AU2012346860A1 (en) | 2014-05-29 |
| AU2012346860B2 (en) | 2015-09-24 |
| US8859765B2 (en) | 2014-10-14 |
| IL232574A0 (en) | 2014-06-30 |
| CN103974932B (zh) | 2016-05-18 |
| TW201335127A (zh) | 2013-09-01 |
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