CN1038127C - 氨基－取代硫醚的制备方法 - Google Patents
氨基－取代硫醚的制备方法 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims description 24
- -1 amino-substituted thioethers Chemical class 0.000 title description 8
- 238000002360 preparation method Methods 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 20
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 7
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- VWIIJDNADIEEDB-UHFFFAOYSA-N 3-methyl-1,3-oxazolidin-2-one Chemical compound CN1CCOC1=O VWIIJDNADIEEDB-UHFFFAOYSA-N 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims description 3
- NCTCGHLIHJJIBK-UHFFFAOYSA-N 3-phenyl-1,3-oxazolidin-2-one Chemical compound O=C1OCCN1C1=CC=CC=C1 NCTCGHLIHJJIBK-UHFFFAOYSA-N 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims 1
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 239000002904 solvent Substances 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
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- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- QPUYECUOLPXSFR-UHFFFAOYSA-N 1-methylnaphthalene Chemical compound C1=CC=C2C(C)=CC=CC2=C1 QPUYECUOLPXSFR-UHFFFAOYSA-N 0.000 description 2
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 2
- QIMMUPPBPVKWKM-UHFFFAOYSA-N 2-methylnaphthalene Chemical compound C1=CC=CC2=CC(C)=CC=C21 QIMMUPPBPVKWKM-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
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- ZWXPDGCFMMFNRW-UHFFFAOYSA-N N-methylcaprolactam Chemical compound CN1CCCCCC1=O ZWXPDGCFMMFNRW-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
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- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
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- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical class 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- NQIZDFMZAXUZCZ-UHFFFAOYSA-N carbifene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OCC)C(=O)N(C)CCN(C)CCC1=CC=CC=C1 NQIZDFMZAXUZCZ-UHFFFAOYSA-N 0.000 description 1
- 229950003365 carbifene Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000011342 chemoimmunotherapy Methods 0.000 description 1
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 1
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- 239000003814 drug Substances 0.000 description 1
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- 239000000975 dye Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 150000003947 ethylamines Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000012943 hotmelt Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- QQVIHTHCMHWDBS-UHFFFAOYSA-N perisophthalic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/24—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/24—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/29—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
通过2-巯基乙醇与通式(Ⅱ)的化合物反应制备式(Ⅰ)化合物，
取代基同说明书中的定义。
Description
本发明涉及氨基-取代硫醚的新的制备方法。这类化合物及其制备是基本上已知的，见Journal of Medicinal Chemistry，1977，Vol.20，Soloway，Chemo-Immuno-Therapy of Cancer，pp.1357 ff.在J.Org.Chem.1992；57.Poindexter，pp.6257-6265中该文献公开了2-噁唑烷酮对芳香族化合物的氨基乙基化作用。
本发明涉及通式(I)化合物的制备方法，
其中R、R1-R6各自独立地表示氢，C1-C4-烷基，由羟基、C1
-C4-烷氧基或SO3H取代的C1-C4-烷基，苯基，苄
基，或由卤素、C1-C4-烷氧基或SO3H取代的苯基或
苄基；且n 代表0或1；该方法的特征在于将2-硫基乙醇与通式(II)化合物反应，
其中R，R1-R6和n，为以上给出的定义。
本反应优选在50℃-250℃，更优选在60℃-200℃的温度下进行。
本反应可选择地在溶剂中进行。
可使用的溶剂是那些pK8值明显比2-巯基乙醇低，且其本身不与2-巯基乙醇反应的所有溶剂，例如烃类、醚类、醇类、羧酰胺类、亚砜类和砜类；胺类除外。
尽管2-噁唑烷酮与苯硫酚的反应是已知的，但至今还没有与烷硫醇成功的反应以生成2-(烷硫基)乙胺化合物(见G.S.Poindexter et al.，J.Org.Chem.1992，57，6257-6265)。
一些式(II)化合物是已知的，可采用Houben-Weyl，Vol.E4(1983)，192-211页中所述的方法制备这些化合物。
式(II)化合物的适当的实例为：
n＝2时：
1-氧代-1，3-噁唑烷(2-噁唑烷酮)，
5-甲基-2-氧代-1，3-噁唑烷，
3-甲基-2-氧代-1，3-噁唑烷，
3-苯基-2-氧代-1，3-噁唑烷，
3-苄基-2-氧代-1，3-噁唑烷，
4-苯基-2-氧代-1，3-噁唑烷，
5-苯基-2-氧代-1，3-噁唑烷，
3，4-二苯基-2-氧代-1，3-噁唑烷，
3，5-二苯基-2-氧代-1，3-噁唑烷，
3，4-二甲基-5-苯基-2-氧代-1，3-噁唑烷，
3-苯基-4-羟甲基-2-氧代-1，3-噁唑烷，
3，5-二甲基-2-氧代-1，3-噁唑烷，
3-乙基-2-氢代-1，3-噁唑烷，
4-乙基-2-氧代-1，3-噁唑烷；
当n＝1时：
四氢[1，3]噁嗪-2-酮，
3-甲基-四氢[1，3]噁嗪-2-酮，
3-苯基-四氢[1，3]噁嗪-2-酮，
3-苄基-四氢[1，3]噁嗪-2-酮，
4-甲基-四氢[1，3]噁嗪-2-酮，
6-甲基-四氢[1，3]噁嗪-2-酮。
优选的方法是制备下述式(I)化合物的方法：其中R 代表氢、甲基、乙基、苯基或苄基；且R1-R6各自独立地表示氢、甲基和苯基，特别是代表氢。
本发明方法更优选实例的特征在于：将式(II)化合物与2-巯基乙醇和碱进行反应，最好用与式(II)化合物等摩尔量的碱，式(II)中R，R1-R6和n具有上述定义。可使用的碱的实例为碱金属或碱土金属碳酸盐、碱金属醇盐或叔胺，优选醇钠和醇钾。
在此碱诱导的不同方法中，优选的温度是50-150℃，特别是60-110℃，且使用的溶剂的实例为N-甲基吡咯烷酮、己内酰胺，N-甲基己内酰胺、环己醇、二甲基亚砜、二甲基砜、环丁砜、甲醇、乙醇、正丙醇、异丙醇、正丁醇、仲丁醇、异丁醇、叔丁醇、水，或所述溶剂的任意混合物。优选甲醇、乙醇、异丙醇和/或水。
这种碱诱导的不同方法特别优选地是用于制备其中n＝D的式(I)化合物。
制备其中n＝0且R和R1-R6为上述给定定义的式(I)化合物的更优选的实例，其特征是将2-巯基乙醇与其中n＝0且R和R1-R6为上述给定定义的式(II)化合物反应。
本发明方法的变异方法优选在100～250℃，特别在150～200℃温度下，可在溶剂中但优选无溶剂存在下进行。对后一方法可使用的适合溶剂的实例为：、萘、1-甲基萘、2-甲基萘、萘烷、1，2，3，4-四氢化萘、对氯苯、硝基苯、联苯、二苯基醚、1-己醇、1-庚醇、1-辛醇、2-辛醇、乙二醇、二甘醇、二甘醇单甲醚、二甘醇单乙基醚、甘油、N-甲基吡咯烷酮、己内酰胺、N-甲基己内酰胺、环己醇、二甲基亚砜、二甲基砜和环丁砜，特别是N-甲基吡咯烷醇、己内酰胺和环丁砜。
根据本发明制备的2-(2′-氨基烷硫基)-乙醇可用作药物和农药的中间体，特别是染料中间体。
本发明的方法特别优选地使用下述式(II)化合物：3-苯基-2-噁唑烷酮、3-甲基-2-噁唑烷酮、2-噁唑烷酮、3-甲基-四氢[1，3]-噁嗪-2-酮或3-苯基-四氢[1，3]噁嗪-2-酮。
实施例1
在160℃，充N2条件下将78.1g 2-巯基乙醇和163g3-苯基-2-噁唑烷酮加热5小时，获得几乎定量产率的2-(2′-苯基氨基乙硫基)乙醇，为浅黄色油，1H NMR谱显示出下述信号：(溶剂D5-DMSO)δ2.58-2.75ppm，6H，m：δ3.22ppm，2H，t：δ4.80ppm，1H，s：δ6.50-6.61ppm，3H，m：δ7.05ppm，2H，d。
实施例2
在160℃，充N2条件下，将156.2g 2-巯基乙醇和202g 3-甲基-2-噁唑烷酮加热5小时。减压蒸馏2-(2′-甲基氨基乙硫基)乙醇，获得无色油；b.p.124℃-130℃/5-6.5mm。
实施例3
将78.1g2-巯基乙醇和87g 2-噁唑烷酮在沸腾的100ml二甘醇单甲醚中加热5小时，减压条件下先蒸馏出溶剂，然后蒸馏2-(2′-氨基乙硫基)乙醇；b.p.117℃-119℃/3mm。
实施例4
将117g 3-苯基-四氢[1，3]噁嗪-2-酮与200ml乙醇一起搅拌，加入70g乙醇钠和80g巯基乙醇，回流条件下加热混合物7小时。反应结束后，蒸馏掉乙醇，剩余物与200ml水一起搅拌。分离出浅黄色油，并鉴定为2-(3′-苯基氨基-正丙基硫基)乙醇。1H NMR(D5-DMSO)：δ1.8ppm，2H，m；δ2.6ppm，4H，m：δ3.09ppm，2H，q：δ3.55ppm，2H，q：δ4.8ppm，1H，1：δ5.56ppm，1H，t；δ6.54ppm，3H，m：δ7.09ppm，2H，m。
实施例5
将74g N-甲基-1，2-乙醇胺，130g碳酸二乙酯和15g乙醇钠，在90℃于50ml乙醇中缓慢加热随后蒸馏掉乙醇，直至残留物的温度达到110℃。将72g巯基乙醇加入到该热熔的混合物中，且混合物在160℃下加热四小时。在140-145℃/20mm蒸馏纯化新得的2-(2′-甲氨基乙硫基)乙醇。1H NMR(D6-DMSO/D2O)：δ2.26ppm，3H，s；δ2.52-2.65，6H，m；δ3.50，2H，t。
Claims (11)
1.制备通式(I)化合物的方法，
其中R、R1-R6各自独立地表示氢，C1-C4-烷基，由羟基C1
-C4-烷氧基或SO3H取代的C1-C4-烷基，苯基，苄
基，或由卤素、C1-C4-烷氧基或SO3H取代的苯基或
苄基：且n 代表0或1：该方法的特征在于将2-巯基乙醇与通式(II)化合物反应，
其中R，R1-R6和n为以上给出的定义。
2.根据权利要求1的方法，其特征在于其中R代表氢、甲基、乙基、苯基或苄基，且R1-R6各自独立地代表氢，甲基和苯基。
3.根据权利要求1的方法，其特征在于取代基R1-R6代表氢.
4.根据权利要求1的方法，其特征在于用碱进行反应.
5.根据权利要求4的方法，其特征在于反应在50-150℃的温度下进行.
6.根据权利要求1的方法，其特征在于用n＝0的式(II)化合物进行反应.
7.根据权利要求6的方法，其特征在于反应在100-250℃的温度下进行.
8.根据权利要求1的方法，其特征在于用与式(II)化合物等摩尔量的碱进行反应.
9.根据权利要求4的方法，其特征在于反应在60-100℃的温度下进行.
10.根据权利要求6的方法，其特征在于反应在150-200℃的温度下进行.
11.根据上述任一权利要求的方法，其特征在于使用的式(II)化合物为3-苯基-2-噁唑烷酮、3-甲基-2-噁唑烷酮、2-噁唑烷酮、3-甲基-四氢[1，3]噁嗪-2-酮或3-苯基-四氢[1，3]噁嗪-2-酮.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19934322053 DE4322053A1 (de) | 1993-07-02 | 1993-07-02 | Verfahren zur Herstellung von aminosubstituierten Thioethern |
| DEP4322053.3 | 1993-07-02 | ||
| DE19934332978 DE4332978A1 (de) | 1993-09-28 | 1993-09-28 | Verfahren zur Herstellung von aminosubstituierten Thioethern |
| DEP4332978.0 | 1993-09-28 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1097739A CN1097739A (zh) | 1995-01-25 |
| CN1038127C true CN1038127C (zh) | 1998-04-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN94108118A Expired - Fee Related CN1038127C (zh) | 1993-07-02 | 1994-07-02 | 氨基－取代硫醚的制备方法 |
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| Country | Link |
|---|---|
| US (1) | US5410081A (zh) |
| EP (1) | EP0632022B1 (zh) |
| JP (1) | JPH0717946A (zh) |
| KR (1) | KR100286845B1 (zh) |
| CN (1) | CN1038127C (zh) |
| DE (1) | DE59401383D1 (zh) |
| TW (1) | TW280812B (zh) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0568876B1 (de) * | 1992-05-04 | 1996-08-28 | Bayer Ag | Reaktivfarbstoffe, deren Herstellung und Verwendung |
| DE4441147A1 (de) * | 1994-11-18 | 1996-05-23 | Hoechst Ag | Verfahren zur Herstellung von 3-(N-Aryl-amino)-propyl-2'-sulfatoethyl-sulfonyl-Verbindungen |
| CN1049623C (zh) * | 1994-12-06 | 2000-02-23 | 叶元龙 | 聚乙烯类板材的熔接方法及其装置 |
| WO1998004534A1 (fr) | 1996-07-31 | 1998-02-05 | Nikken Chemicals Co., Ltd. | Derives de 6-phenyltetrahydro-1,3-oxazine-2-one et compositions medicinales a base de ces composes |
| AR057218A1 (es) * | 2005-12-15 | 2007-11-21 | Astra Ab | Compuestos de oxazolidinona y su uso como pontenciadores del receptor metabotropico de glutamato |
| JP5486928B2 (ja) * | 2007-02-26 | 2014-05-07 | ヴァイティー ファーマシューティカルズ，インコーポレイテッド | １１β−ヒドロキシステロイドデヒドロゲナーゼ１のサイクリックウレアおよびカルバメートインヒビター |
| ES2395081T3 (es) * | 2007-07-26 | 2013-02-08 | Vitae Pharmaceuticals, Inc. | Síntesis de inhibidores de la 11beta-hidroxiesteroide deshidrogenasa de tipo 1 |
| AR069207A1 (es) * | 2007-11-07 | 2010-01-06 | Vitae Pharmaceuticals Inc | Ureas ciclicas como inhibidores de la 11 beta - hidroxi-esteroide deshidrogenasa 1 |
| EP2229368A1 (en) | 2007-12-11 | 2010-09-22 | Vitae Pharmaceuticals, Inc. | Cyclic urea inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| TW200934490A (en) * | 2008-01-07 | 2009-08-16 | Vitae Pharmaceuticals Inc | Lactam inhibitors of 11 &abgr;-hydroxysteroid dehydrogenase 1 |
| JP5490020B2 (ja) * | 2008-01-24 | 2014-05-14 | ヴァイティー ファーマシューティカルズ，インコーポレイテッド | １１β−ヒドロキシステロイドデヒドロゲナーゼ１の環状カルバゼート及びセミカルバジドインヒビター |
| WO2009102428A2 (en) * | 2008-02-11 | 2009-08-20 | Vitae Pharmaceuticals, Inc. | 1,3-OXAZEPAN-2-ONE AND 1,3-DIAZEPAN-2-ONE INHIBITORS OF 11β -HYDROXYSTEROID DEHYDROGENASE 1 |
| CA2715290A1 (en) * | 2008-02-15 | 2009-08-20 | Vitae Pharmaceuticals, Inc. | Inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| JP5538356B2 (ja) * | 2008-03-18 | 2014-07-02 | ヴァイティー ファーマシューティカルズ，インコーポレイテッド | １１β−ヒドロキシステロイドデヒドロゲナーゼ１型の阻害剤 |
| WO2009134387A1 (en) | 2008-05-01 | 2009-11-05 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| WO2009134384A1 (en) * | 2008-05-01 | 2009-11-05 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| WO2009134392A1 (en) | 2008-05-01 | 2009-11-05 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| JP5301563B2 (ja) | 2008-05-01 | 2013-09-25 | ヴァイティー ファーマシューティカルズ，インコーポレイテッド | １１β−ヒドロキシステロイドデヒドロゲナーゼ１の環状インヒビター |
| EP2324018B1 (en) | 2008-07-25 | 2013-09-04 | Boehringer Ingelheim International GmbH | Cyclic inhibitors of 11 beta-hydroxysteroid dehydrogenase 1 |
| CA2729998A1 (en) | 2008-07-25 | 2010-01-28 | Boehringer Ingelheim International Gmbh | Inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| EP2393807B1 (en) | 2009-02-04 | 2013-08-14 | Boehringer Ingelheim International GmbH | Cyclic inhibitors of 11 -hydroxysteroid dehydrogenase 1 |
| TW201039034A (en) * | 2009-04-27 | 2010-11-01 | Chunghwa Picture Tubes Ltd | Pixel structure and the method of forming the same |
| MA33216B1 (fr) | 2009-04-30 | 2012-04-02 | Boehringer Ingelheim Int | Inhibiteurs cycliques de la 11béta-hydroxysteroïde déshydrogénase 1 |
| KR20120061771A (ko) * | 2009-04-30 | 2012-06-13 | 비타이 파마슈티컬즈, 인코포레이티드 | 11베타-하이드록시스테로이드 탈수소효소 1의 고리형 억제제 |
| US8927539B2 (en) | 2009-06-11 | 2015-01-06 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11β-hydroxysteroid dehydrogenase 1 based on the 1,3-oxazinan-2-one structure |
| EP2448928B1 (en) | 2009-07-01 | 2014-08-13 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| EP2582698B1 (en) | 2010-06-16 | 2016-09-14 | Vitae Pharmaceuticals, Inc. | Substituted 5-,6- and 7-membered heterocycles, medicaments containing such compounds, and their use |
| EP2585444B1 (en) | 2010-06-25 | 2014-10-22 | Boehringer Ingelheim International GmbH | Azaspirohexanones as inhibitors of 11-beta-hsd1 for the treatment of metabolic disorders |
| EA201300522A1 (ru) | 2010-11-02 | 2013-11-29 | Бёрингер Ингельхайм Интернациональ Гмбх | Фармацевтические комбинации для лечения метаболических нарушений |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0498765A1 (de) * | 1991-02-04 | 1992-08-12 | Ciba-Geigy Ag | Verfahren zur Herstellung von Alkyl- und Arylthiocarbonsäuren und deren Estern |
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| US3950542A (en) * | 1967-02-21 | 1976-04-13 | L'oreal | Cysteamine derivatives for oral treatment of seborrhea |
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- 1994-06-03 TW TW083105060A patent/TW280812B/zh active
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- 1994-06-21 EP EP94109543A patent/EP0632022B1/de not_active Expired - Lifetime
- 1994-06-24 US US08/265,525 patent/US5410081A/en not_active Expired - Lifetime
- 1994-06-27 JP JP6165760A patent/JPH0717946A/ja active Pending
- 1994-07-01 KR KR1019940015725A patent/KR100286845B1/ko not_active IP Right Cessation
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0498765A1 (de) * | 1991-02-04 | 1992-08-12 | Ciba-Geigy Ag | Verfahren zur Herstellung von Alkyl- und Arylthiocarbonsäuren und deren Estern |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0632022A3 (en) | 1995-02-01 |
| EP0632022B1 (de) | 1996-12-27 |
| KR100286845B1 (ko) | 2001-04-16 |
| KR950003267A (ko) | 1995-02-16 |
| JPH0717946A (ja) | 1995-01-20 |
| US5410081A (en) | 1995-04-25 |
| DE59401383D1 (de) | 1997-02-06 |
| EP0632022A2 (de) | 1995-01-04 |
| TW280812B (zh) | 1996-07-11 |
| CN1097739A (zh) | 1995-01-25 |
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