JP2015505827A5 - - Google Patents
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- JP2015505827A5 JP2015505827A5 JP2014543996A JP2014543996A JP2015505827A5 JP 2015505827 A5 JP2015505827 A5 JP 2015505827A5 JP 2014543996 A JP2014543996 A JP 2014543996A JP 2014543996 A JP2014543996 A JP 2014543996A JP 2015505827 A5 JP2015505827 A5 JP 2015505827A5
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- JP
- Japan
- Prior art keywords
- compound
- formula
- group
- benzyl
- iii
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims description 142
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 56
- 238000000034 method Methods 0.000 claims description 49
- 150000003839 salts Chemical class 0.000 claims description 39
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 37
- 229940124530 sulfonamide Drugs 0.000 claims description 33
- 150000003456 sulfonamides Chemical class 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 239000003638 chemical reducing agent Substances 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 25
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 20
- 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 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 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
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 150000007513 acids Chemical class 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 229910052725 zinc Inorganic materials 0.000 claims description 9
- 239000011701 zinc Substances 0.000 claims description 9
- 150000003460 sulfonic acids Chemical class 0.000 claims description 8
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 claims description 7
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 7
- 239000011707 mineral Substances 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 claims description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052987 metal hydride Inorganic materials 0.000 claims description 6
- 150000004681 metal hydrides Chemical class 0.000 claims description 6
- 150000001735 carboxylic acids Chemical class 0.000 claims description 5
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 3
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
- 229910001092 metal group alloy Inorganic materials 0.000 claims description 2
- 150000002739 metals Chemical class 0.000 claims 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 238000006243 chemical reaction Methods 0.000 description 44
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 40
- 239000003054 catalyst Substances 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 0 CC1(C)C2(CS)*(*)(*)CC1CC2 Chemical compound CC1(C)C2(CS)*(*)(*)CC1CC2 0.000 description 33
- 239000000243 solution Substances 0.000 description 32
- 239000000203 mixture Substances 0.000 description 30
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 25
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 23
- 150000003573 thiols Chemical class 0.000 description 23
- 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 21
- 238000003786 synthesis reaction Methods 0.000 description 18
- ZDJVMVOTNCGCHC-PGCMWVOQSA-N [(1r,3r,4s)-7,7-dimethyl-3-morpholin-4-yl-4-bicyclo[2.2.1]heptanyl]methanethiol;hydrochloride Chemical compound Cl.N1([C@H]2[C@@]3(CC[C@](C2)(C3(C)C)[H])CS)CCOCC1 ZDJVMVOTNCGCHC-PGCMWVOQSA-N 0.000 description 17
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 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
- 238000000746 purification Methods 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 150000002019 disulfides Chemical class 0.000 description 10
- 150000002081 enamines Chemical class 0.000 description 10
- 239000003446 ligand Substances 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 238000007259 addition reaction Methods 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 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 8
- 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 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 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 7
- 238000005755 formation reaction Methods 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 7
- 150000002894 organic compounds Chemical class 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- AGOIXAWNNBQPGF-JYARDEAWSA-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;hydrochloride Chemical compound Cl.C([C@@]12CC[C@](C[C@H]2N2CCOCC2)(C1(C)C)[H])SSCC1(C2(C)C)CCC2CC1N1CCOCC1 AGOIXAWNNBQPGF-JYARDEAWSA-N 0.000 description 6
- QTUXJUFXEFPEEW-WBVHZDCISA-N CC(C)([C@H](CC1)CC2(N3CCOCC3)N3CCOCC3)[C@@]12NS(C)(=O)=O Chemical compound CC(C)([C@H](CC1)CC2(N3CCOCC3)N3CCOCC3)[C@@]12NS(C)(=O)=O QTUXJUFXEFPEEW-WBVHZDCISA-N 0.000 description 6
- 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
- 238000011914 asymmetric synthesis Methods 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 150000001728 carbonyl compounds Chemical class 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- 239000005909 Kieselgur Substances 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- 235000010755 mineral Nutrition 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 230000009466 transformation Effects 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
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-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
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 238000007294 asymmetric addition reaction Methods 0.000 description 4
- LUFPJJNWMYZRQE-UHFFFAOYSA-N benzylsulfanylmethylbenzene Chemical compound C=1C=CC=CC=1CSCC1=CC=CC=C1 LUFPJJNWMYZRQE-UHFFFAOYSA-N 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 238000011097 chromatography purification Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 150000003840 hydrochlorides Chemical class 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- WPKPEWUGTSGLPD-KBXCAEBGSA-N n-[(1r,4s)-7,7-dimethyl-2,3-dimorpholin-4-yl-4-bicyclo[2.2.1]hept-2-enyl]methanesulfonamide Chemical compound C=1([C@@]2(CC[C@@](C=1N1CCOCC1)(C2(C)C)[H])NS(C)(=O)=O)N1CCOCC1 WPKPEWUGTSGLPD-KBXCAEBGSA-N 0.000 description 4
- 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 4
- NUQVQAFTAAEOOG-RHSMWYFYSA-N n-benzyl-1-[(1r,4s)-3-hydroxyimino-7,7-dimethyl-4-bicyclo[2.2.1]heptanyl]methanesulfonamide Chemical compound C([C@@]12CC[C@](CC2=NO)(C1(C)C)[H])S(=O)(=O)NCC1=CC=CC=C1 NUQVQAFTAAEOOG-RHSMWYFYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 125000001424 substituent group Chemical group 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
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- CYPSAVQLHRECFC-UHFFFAOYSA-N CC(C)C(C(C1)C2)C1(CS)C2N1CCOCC1 Chemical compound CC(C)C(C(C1)C2)C1(CS)C2N1CCOCC1 CYPSAVQLHRECFC-UHFFFAOYSA-N 0.000 description 3
- 229910010082 LiAlH Inorganic materials 0.000 description 3
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical group [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000004587 chromatography analysis 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
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 238000004305 normal phase HPLC Methods 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- ABOYDMHGKWRPFD-UHFFFAOYSA-N phenylmethanesulfonamide Chemical class NS(=O)(=O)CC1=CC=CC=C1 ABOYDMHGKWRPFD-UHFFFAOYSA-N 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- 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
- SKVBDSLAVOGEQE-UHFFFAOYSA-N CC(C)(C(C1)C2)C1(CSSCC1(C3)C(C)(C)C3CC1N1CCOCC1)C2N1CCOCC1 Chemical compound CC(C)(C(C1)C2)C1(CSSCC1(C3)C(C)(C)C3CC1N1CCOCC1)C2N1CCOCC1 SKVBDSLAVOGEQE-UHFFFAOYSA-N 0.000 description 2
- KQCZHEAGLXKWRD-UHFFFAOYSA-N CC(C)C(C(C1)C2)C1(CS(NCc1ccccc1)(=O)=O)C2N1CCOCC1 Chemical compound CC(C)C(C(C1)C2)C1(CS(NCc1ccccc1)(=O)=O)C2N1CCOCC1 KQCZHEAGLXKWRD-UHFFFAOYSA-N 0.000 description 2
- RMJGXAPCCPYPJO-UHFFFAOYSA-N CC(C)C(C(C1)C2)C1(CSSCC1(C3)C(C)(C)C3CC1N1CCOCC1)C2N1CCOCC1 Chemical compound CC(C)C(C(C1)C2)C1(CSSCC1(C3)C(C)(C)C3CC1N1CCOCC1)C2N1CCOCC1 RMJGXAPCCPYPJO-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
- 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
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-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
- 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
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 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
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- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 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
- 230000035945 sensitivity Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 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 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- CMWCOKOTCLFJOP-UHFFFAOYSA-N titanium(3+) Chemical class [Ti+3] CMWCOKOTCLFJOP-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000009901 transfer hydrogenation reaction Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000006886 vinylation reaction Methods 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
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| PCT/IB2012/002910 WO2013080049A2 (en) | 2011-11-30 | 2012-11-29 | A process for the manufacture of chiral catalysts and their salts |
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| 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 |
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| TW201136904A (en) * | 2010-04-30 | 2011-11-01 | Nat Univ Tsing Hua | Method for preparing 2-morpholinoisobornane-10-thiol and intermediates formed therein |
| 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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