CN112500419A - Epoxy fused 2-methylene pyrrolidine compound and preparation method thereof - Google Patents
Epoxy fused 2-methylene pyrrolidine compound and preparation method thereof Download PDFInfo
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- CN112500419A CN112500419A CN202011321553.9A CN202011321553A CN112500419A CN 112500419 A CN112500419 A CN 112500419A CN 202011321553 A CN202011321553 A CN 202011321553A CN 112500419 A CN112500419 A CN 112500419A
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- methylene
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- azabicyclo
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- hexane
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- -1 2-methylene pyrrolidine compound Chemical class 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000004593 Epoxy Substances 0.000 title claims description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- CPHUUWJMAOTJLB-UHFFFAOYSA-N 2-methylidenepyrrolidine Chemical class C=C1CCCN1 CPHUUWJMAOTJLB-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- 150000001335 aliphatic alkanes Chemical class 0.000 claims abstract 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 96
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 11
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 239000002585 base Substances 0.000 claims description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 8
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 238000010898 silica gel chromatography Methods 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- SSVFMICWXDVRQN-UHFFFAOYSA-N ethanol;sodium Chemical compound [Na].CCO SSVFMICWXDVRQN-UHFFFAOYSA-N 0.000 claims 1
- BHLUERUPCAAQGF-UHFFFAOYSA-N prop-2-yne-1-thiol Chemical class SCC#C BHLUERUPCAAQGF-UHFFFAOYSA-N 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 125000000524 functional group Chemical group 0.000 abstract 1
- PKDGTVRRRFCLLK-UHFFFAOYSA-N 4-methyl-n-phenacylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NCC(=O)C1=CC=CC=C1 PKDGTVRRRFCLLK-UHFFFAOYSA-N 0.000 description 20
- 238000000034 method Methods 0.000 description 18
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- WUHKVBHEWPBWAS-UHFFFAOYSA-M dimethyl(prop-2-ynyl)sulfanium;bromide Chemical compound [Br-].C[S+](C)CC#C WUHKVBHEWPBWAS-UHFFFAOYSA-M 0.000 description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000001308 synthesis method Methods 0.000 description 5
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 229930014626 natural product Natural products 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- YFEYDNAKCSOOOG-YCXOGWGTSA-N (2S,3R,4S,5S)-3-tert-butyl-4-[[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1[C@H](N([C@H]([C@H]1OCC=1C(=NC=C(C=1)C(F)(F)F)OC)C1=C(C=CC=C1)C)C(=O)[C@H]1OCCCC1)C(=O)O YFEYDNAKCSOOOG-YCXOGWGTSA-N 0.000 description 1
- DTEAMMSJXLXUOQ-UHFFFAOYSA-N 1-hydroxyaziridine Chemical compound ON1CC1 DTEAMMSJXLXUOQ-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- BOWRPOPAWLWONG-UHFFFAOYSA-M [Br-].C[S+](CC#CC1=CC=CC=C1)C Chemical compound [Br-].C[S+](CC#CC1=CC=CC=C1)C BOWRPOPAWLWONG-UHFFFAOYSA-M 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 238000006535 aza-Payne rearrangement reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 238000005913 hydroamination reaction Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- NGWSFRIPKNWYAO-SHTIJGAHSA-N salinosporamide A Chemical compound C([C@@H]1[C@H](O)[C@]23C(=O)O[C@]2([C@H](C(=O)N3)CCCl)C)CCC=C1 NGWSFRIPKNWYAO-SHTIJGAHSA-N 0.000 description 1
- NGWSFRIPKNWYAO-UHFFFAOYSA-N salinosporamide A Natural products N1C(=O)C(CCCl)C2(C)OC(=O)C21C(O)C1CCCC=C1 NGWSFRIPKNWYAO-UHFFFAOYSA-N 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Abstract
本申请公开了一种环氧稠合的2‑亚甲基吡咯烷类化合物，其结构式为：所述R1为氢，甲基，苯基，R2为各种取代的苯基、烷烃基或者杂环芳基等。本发明还同时公开了上述环氧稠合的2‑亚甲基吡咯烷类化合物的制备方法，在一定温度下，磺酰基保护的β‑氨基酮衍生物及丙‑2‑炔基锍盐类化合物在相应碱的作用下发生反应合成环氧稠合的2‑亚甲基吡咯烷类化合物。本发明提供的制备方法具有操作简单，原料易得，反应条件温和，反应的官能团耐受性好，产物产率优良且分离等优点。The application discloses an epoxy-fused 2-methylene pyrrolidine compound, the structural formula of which is: 
The R1 is hydrogen, methyl, phenyl, and R2 is various substituted phenyl, alkane or heterocyclic aryl, etc. The invention also discloses a preparation method of the above epoxy-fused 2-methylene pyrrolidine compounds. At a certain temperature, the sulfonyl-protected β-amino ketone derivatives and prop-2-alkynyl sulfonium salts The compound reacts under the action of a corresponding base to synthesize epoxy-fused 2-methylenepyrrolidine compounds. The preparation method provided by the invention has the advantages of simple operation, readily available raw materials, mild reaction conditions, good tolerance of the reacted functional groups, excellent product yield and separation, and the like.
Description
Technical Field
The application relates to a synthesis method of a compound, in particular to an epoxy fused 2-methylene pyrrolidine compound and a preparation method thereof.
Background
Five-membered nitrogen heterocycles (pyrrolidine and pyrrole) are important structures in many natural products and bioactive molecules, such as (-) -slaflumamine, ABBV-3221 and the like, all have pyrrolidine or pyrrole mother nuclei, and the structural formula is as follows:
in particular, epoxy fused 2-methylene pyrrolidine is a very important skeleton structure and can be used as a fast-constructed synthon of natural products containing pyrrolidine and pyrrolidone structures. Currently, only the Borhan group reported a strategy for constructing epoxy-fused 2-methylenepyrrolidine units from aziridinol via a one-pot tandem aza Payne/hydroamination reaction, and used this strategy in the total synthesis of the natural product (-) -Salinosporamide A, as shown below:
but the preparation of the initial raw material is relatively complex, a Grignard reagent is needed to participate, and the preparation conditions are strict; the raw materials have the requirement of three-dimensional configuration; the post-reaction treatment process is relatively complicated. Therefore, the development of new strategies for simpler construction of these epoxy-fused 2-methylenepyrrolidines using commercial reagents has certain value and significance.
Disclosure of Invention
The embodiment of the application aims to provide an epoxy fused 2-methylene pyrrolidine compound and a preparation method thereof, so as to solve the problems of difficult obtainment of raw materials and complex post-treatment process in the related art.
According to a first aspect of embodiments herein there is provided an epoxy-fused 2-methylenepyrrolidine compound of the formula:
wherein R is1Is hydrogen, methyl or phenyl, R2Is various substituted phenyl, alkyl or heterocyclic aryl.
According to a second aspect of embodiments herein, there is provided a process for the preparation of an epoxy-fused 2-methylenepyrrolidine compound comprising the steps of:
dissolving sulfonyl protected beta-aminoketone derivative, alkali and a prop-2-alkynyl sulfonium salt compound in a solvent, and stirring overnight at the temperature of 0-100 ℃ until the reaction of the raw materials is finished;
the structural formula of the propyl-2-alkynyl sulfonium salt compound is as follows:
the R is1Is hydrogen, methyl or phenyl;
the structural formula of the sulfonyl protected beta-aminoketone derivative is as follows:
the R is2Is various substituted phenyl, alkyl or heterocyclic aryl;
and (2) filtering the reaction system obtained in the step (1), and concentrating the filtrate under reduced pressure to obtain a residue. Separating and purifying the residue by silica gel column chromatography to obtain epoxy fused 2-methylene pyrrolidine compounds, wherein the structural formula of the epoxy fused 2-methylene pyrrolidine compounds is as follows:
further, in the step (1), 1.0 equivalent of the sulfonyl group-protected β -aminoketone derivative, the base, and the prop-2-ynylsulfonium salt compound are dissolved in a solvent.
Further, in the step (1), the mixture is stirred at 0 ℃, 0-10 ℃, 30 ℃, 40 ℃, 80 ℃ and 100 ℃, preferably 0-10 ℃.
Further, the solvent is toluene, 1, 4-dioxane, tetrahydrofuran, dichloromethane, acetonitrile, N, N-dimethylformamide, dimethyl sulfoxide and methanol; the solvent is preferably dichloromethane.
Further, the base is potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, sodium ethoxide, 1, 8-diazabicycloundecen-7-ene (DBU), pyridine, N-Diisopropylethylamine (DIEA), triethylamine, 4-Dimethylaminopyridine (DMAP), with cesium carbonate being preferred.
Further, the base is used in an amount of 1.5 to 7.0 equivalents, of the sulfonyl group-protected β -aminoketone derivative, with 2.0 equivalents being preferred.
Further, the prop-2-ynylsulfonium salt compound is used in an amount of 1.5 to 7.0 equivalents, of the sulfonyl group-protected β -aminoketone derivative, with an equivalent of 2.0 equivalents being preferred.
Further, the petroleum ether in the silica gel column chromatography, ethyl acetate, is 10: 1.
The technical scheme provided by the embodiment of the application can have the following beneficial effects:
from the above examples, it can be seen that the epoxy fused 2-methylene pyrrolidine compounds with novel structure can be obtained by dissolving the sulfonyl protected beta-aminoketone derivative, the base and the propyl-2-alkynyl sulfonium salt compound in dichloromethane, and stirring at 0-10 ℃ until the raw materials are reacted. The synthesis method has the advantages of high yield, convenient post-treatment, no need of heavy/noble metal catalyst, mild reaction conditions and easily obtained reaction raw materials, and provides a simple, easy and efficient synthesis method for obtaining the epoxy fused 2-methylene pyrrolidine compound. In addition, the synthesis method of the invention is not reported in the literature.
The synthesis method of the epoxy fused 2-methylene pyrrolidine compound provided by the invention has the following characteristics: 1. no heavy/noble metal catalyst is needed; 2. the reaction condition is mild; 3. the reaction yield is high, the separation is easy, and the separation yield of most products is over 70 percent; 4. the substrate has wide applicability, and various substrate structures can bear the reaction conditions.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the application.
Detailed Description
Exemplary embodiments will be described in detail herein. The implementations described in the following exemplary embodiments do not represent all implementations consistent with the present application. Rather, they are merely examples of apparatus and methods consistent with certain aspects of the present application, as detailed in the appended claims.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in this application and the appended claims, the singular forms "a", "an", and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the term "and/or" as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items.
Example 1: (1R, 5S/1S,5R) -4-methylene-1-phenyl-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide (0.5mmol,1.0 equiv.), cesium carbonate (1.0mmol,2.0 equiv.), and dimethyl (prop-2-yn-1-yl) sulfonium bromide salt (1.0mmol,2.0 equiv.) were dissolved in 10mL of dichloromethane and stirred at 0-10 deg.C overnight until the starting material was reacted. After the reaction is finished, filtering the reaction system, and concentrating the filtrate under reduced pressure to obtain a residue. The residue was isolated and purified by silica gel column chromatography (petroleum ether: ethyl acetate 10:1) to give a yellow oil in 86% yield.
Yellow oil, yield 86%.1H NMR(400MHz,DMSO)δ7.72(d,J＝8.3Hz, 2H),7.42(s,1H),7.40(s,1H),7.39-7.33(m,5H),5.20(s,1H),4.92 (s,1H),4.35(d,J＝12.4Hz,1H),4.26(s,1H),4.18(d,J＝12.4Hz, 1H),2.39(s,3H)。13C NMR(100MHz,DMSO)δ144.3,141.9,134.3,132.8, 129.7,128.9,128.7,127.5,126.4,97.8,64.3,63.5,52.4,21.1。HRMS (ESI)calcd for C18H18NO3S(M+H)+:328.1002,found:328.1003。
Example 1 comparison of yields under different solvent conditions
Example 1 comparison of yields under different base conditions
Example 1 Cs in different ratios 1:22CO3Comparison of yield under the conditions
Example 1 comparison of yields at different temperatures
Example 2: (1R, 5S/1S,5R) -4-methylene-1-phenyl-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide (0.1mmol,1.0 equiv.), cesium carbonate (0.15mmol,1.5 equiv.), and dimethyl (prop-2-yn-1-yl) sulfonium bromide salt (0.15mmol,1.5 equiv.) were dissolved in 1mL acetonitrile and stirred overnight at 20 ℃ until the starting material was reacted. After the reaction was complete, the yield was calculated by HPLC analysis to be 45%. The solvent may be any one of toluene, 1, 4-dioxane, tetrahydrofuran, N-dimethylformamide, dimethyl sulfoxide and methanol, in addition to acetonitrile.
Example 3: (1R, 5S/1S,5R) -4-methylene-1-phenyl-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide (0.1mmol,1.0 equiv.), 1, 8-diazabicycloundec-7-ene (0.15mmol,1.5 equiv.), and dimethyl (prop-2-yn-1-yl) sulfonium bromide salt (0.15mmol,1.5 equiv.) were dissolved in 1mL of dichloromethane and stirred overnight at 20 ℃ until the starting material was reacted. After the reaction was complete, the yield was calculated by HPLC analysis to be 47%. In addition to 1, 8-diazabicycloundecen-7-ene (DBU), the base may also be selected from potassium carbonate, sodium hydroxide, sodium ethoxide, pyridine, N, N-Diisopropylethylamine (DIEA), triethylamine, 4-Dimethylaminopyridine (DMAP).
Example 4: (1R, 5S/1S,5R) -4-methylene-1-phenyl-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide (0.1mmol,1.0 equiv.), cesium carbonate (0.15mmol,1.5 equiv.), and dimethyl (prop-2-yn-1-yl) sulfonium bromide salt (0.15mmol,1.5 equiv.) were dissolved in 1mL of dichloromethane and stirred overnight at 20 deg.C until the starting material was reacted. After the reaction was completed, the yield was calculated by HPLC analysis to be 56%.
Example 5: (1R, 5S/1S,5R) -4-methylene-1-phenyl-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide (0.1mmol,1.0 equiv.), cesium carbonate (0.15mmol,1.5 equiv.), and dimethyl (prop-2-yn-1-yl) sulfonium bromide salt (0.7mmol,7 equiv.) were dissolved in 1mL of dichloromethane and stirred overnight at 20 ℃ until the starting material was reacted. After the reaction was completed, the yield was calculated by HPLC analysis to be 36%.
Example 6: (1R, 5S/1S,5R) -4-methylene-1-phenyl-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide (0.1mmol,1.0 equiv.), cesium carbonate (0.7mmol,7 equiv.), and dimethyl (prop-2-yn-1-yl) sulfonium bromide salt (0.2mmol,2 equiv.) were dissolved in 1mL of dichloromethane and stirred overnight at 20 deg.C until the starting material was reacted. After the reaction was completed, the yield was calculated by HPLC analysis to be 54%.
Example 7: (1R, 5S/1S,5R) -4-methylene-1-phenyl-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide (0.1mmol,1.0 equiv.), cesium carbonate (0.2mmol,2 equiv.), and dimethyl (prop-2-yn-1-yl) sulfonium bromide salt (0.2mmol,2 equiv.) were dissolved in 1mL of dichloromethane and stirred at 0 deg.C overnight until the starting material was reacted. After the reaction was completed, the yield was calculated by HPLC analysis to be 60%.
Example 8: (1R, 5S/1S,5R) -4-methylene-1-phenyl-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide (0.1mmol,1.0 equiv.), cesium carbonate (0.2mmol,2 equiv.), and dimethyl (prop-2-yn-1-yl) sulfonium bromide salt (0.2mmol,2 equiv.) were dissolved in 1mL of dichloromethane and stirred overnight at 100 deg.C until the starting material was reacted. After the reaction was completed, the yield was calculated by HPLC analysis to be 31%.
Example 9: (1R, 5S/1S,5R) -1- (4-fluorophenyl) -4-methylene-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1, except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced by N- (2- (4-fluorophenyl) -2-oxyethyl) -4-methylbenzenesulfonamide to give a yellow oil with a yield of 96%.
Yellow oil, yield 96%.1H NMR(400MHz,DMSO)δ7.72(d,J＝8.2Hz, 2H),7.46(dd,J＝8.8,5.4Hz,2H),7.41(d,J＝8.1Hz,2H),7.22(t, J＝8.9Hz,2H),5.20(s,1H),4.91(s,1H),4.36(d,J＝12.4Hz,1H), 4.28(s,1H),4.20(d,J＝12.5Hz,1H),2.39(s,3H)。13C NMR(100MHz, DMSO)δ163.2(d,J＝244Hz),144.2,141.8,134.2,129.7,129.1(d, J＝2.9Hz),128.8(d,J＝8.4Hz),127.5,115.6(d,J＝21.6Hz),97.8, 64.2,63.1,52.4,21.1。HRMS(ESI)calcd for C18H17FNO3S(M+H)+:346.0908, found:346.0910。
Example 10: (1R, 5S/1S,5R) -1- (4-chlorophenyl) -4-methylene-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1 except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced by N- (2- (4-chlorophenyl) -2-oxyethyl) -4-methylbenzenesulfonamide to give a yellow oil in 82% yield.
Yellow oil, yield 82%.1H NMR(400MHz,DMSO)δ7.72(d,J＝8.2Hz, 2H),7.48-7.43(m,4H),7.41(s,1H),7.39(s,1H),5.21(s,1H),4.91 (s,1H),4.37(d,J＝12.5Hz,1H),4.28(s,1H),4.19(d,J＝12.4Hz, 1H),2.39(s,3H)。13C NMR(100MHz,DMSO)δ144.2,141.7,134.2,133.6, 131.8,129.7,128.6,128.4,127.5,97.9,64.4,63.0,52.3,21.1。HRMS (ESI)calcd for C18H17ClNO3S(M+H)+:362.0612,found:362.0607。
Example 11: (1R, 5S/1S,5R) -1- (4-bromophenyl) -4-methylene-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1 except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced by N- (2- (4-bromophenyl) -2-oxyethyl) -4-methylbenzenesulfonamide to give a yellow oil with a yield of 50%.
Yellow oil, yield 50%.1H NMR(400MHz,DMSO)δ7.72(d,J＝8.3Hz, 2H),7.59(d,J＝8.5Hz,2H),7.41(d,J＝8.1Hz,2H),7.37(d,J＝ 8.5Hz,2H),5.20(s,1H),4.91(s,1H),4.37(d,J＝12.5Hz,1H),4.28 (s,1H),4.19(d,J＝12.4Hz,1H),2.39(s,3H)。13C NMR(100MHz,DMSO) δ144.2,141.7,134.2,132.3,131.5,129.7,128.7,127.5,122.1,97.9, 64.4,63.1,52.2,21.1。HRMS(ESI)calcd for C18H17BrNO3S(M+H)+:406.0107, found:406.0110。
Example 12: (1R, 5S/1S,5R) -4-methylene-3-tolyl-1- (4- (trifluoromethyl) phenyl) -6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1, except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced by 4-methyl-N- (2-oxo-2- (4- (trifluoromethyl) phenyl) ethyl) benzenesulfonamide to give a yellow solid in 63% yield.
Yellow solid, yield 63%.1H NMR(400MHz,DMSO)δ7.76(s,1H),7.74(s, 2H),7.72(s,1H),7.64(d,J＝8.2Hz,2H),7.41(d,J＝8.2Hz,2H), 5.23(s,1H),4.93(s,1H),4.46(d,J＝12.5Hz,1H),4.33(s,1H),4.23 (d,J＝12.6Hz,1H),2.40(s,3H)。13C NMR(100MHz,DMSO)δ144.3,141.6, 137.6,134.2,129.7,129.2(d,J＝32.1Hz),127.5,127.4,125.5(q,J ＝3.8Hz),98.1,64.7,63.0,52.2,21.1。HRMS(ESI)calcd for C19H17F3NO3S (M+H)+:396.0876,found:396.0877。
Example 13: (1R, 5S/1S,5R) -4-methylene-1- (4-nitrophenyl) -3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1 except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced with 4-methyl-N- (2- (4-nitrophenyl) -2-oxyethyl) benzenesulfonamide to give a white solid with a yield of 51%.
White solid, yield 51%.1H NMR(400MHz,DMSO)δ8.23(d,J＝8.9Hz, 2H),7.71(dd,J＝12.5,8.6Hz,4H),7.42(d,J＝8.0Hz,2H),5.24(s, 1H),4.94(s,1H),4.50(d,J＝12.5Hz,1H),4.36(s,1H),4.25(d,J ＝12.5Hz,1H),2.40(s,3H)。13C NMR(100MHz,DMSO)δ147.6,144.3, 141.4,140.3,134.1,129.7,127.9,127.5,123.6,98.3,65.1,63.0,52.1, 21.1。HRMS(ESI)calcd for C18H17N2O5S(M+H)+:373.0853,found:373.0845。
Example 14: (1R, 5S/1S,5R) -4-methylene-1- (p-tolyl) -3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1, except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced by 4-methyl-N- (2-oxo-2- (p-tolyl) ethyl) benzenesulfonamide to give a yellow oil in 82% yield.
Yellow oil, yield 82%.1H NMR(400MHz,DMSO)δ7.73(d,J＝8.3Hz, 2H),7.40(d,J＝8.1Hz,2H),7.28(d,J＝8.1Hz,2H),7.19(d,J＝ 8.1Hz,2H),5.20(s,1H),4.90(s,1H),4.33(d,J＝12.4Hz,1H),4.24 (s,1H),4.17(d,J＝12.4Hz,1H),2.39(s,3H),2.29(s,3H)。13C NMR (100MHz,DMSO)δ144.2,141.9,138.3,134.2,129.7,129.7,129.2,127.5, 126.3,97.6,64.1,63.4,52.4,21.1,20.8。HRMS(ESI)calcd for C19H20NO3S (M+H)+:342.1158,found:342.1158。
Example 15: (1R, 5S/1S,5R) -1- (4-methoxyphenyl) -4-methylene-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1, except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced by N- (2- (4-methoxyphenyl) -2-oxyethyl) -4-methylbenzenesulfonamide to give a yellow oil in 89% yield.
Yellow oil, 89% yield.1H NMR(400MHz,DMSO)δ7.72(d,J＝8.3Hz, 2H),7.41(d,J＝8.1Hz,2H),7.32(d,J＝8.7Hz,2H),6.93(d,J＝ 8.8Hz,2H),5.19(s,1H),4.89(s,1H),4.30(d,J＝12.4Hz,1H),4.25 (s,1H),4.19(s,1H),3.74(s,3H),2.39(s,3H)。13C NMR(100MHz,DMSO) δ159.6,144.2,142.0,134.2,129.7,127.9,127.5,124.5,114.0,97.5, 64.0,63.3,55.3,52.5,21.1。HRMS(ESI)calcd for C19H20NO4S(M+H)+: 358.1108,found:358.1105。
Example 16: (1R, 5S/1S,5R) -1- (3-bromophenyl) -4-methylene-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1 except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced by N- (2- (3-bromophenyl) -2-oxyethyl) -4-methylbenzenesulfonamide to give a yellow oil in 63% yield.
Yellow oil, yield 63%.1H NMR(400MHz,DMSO)δ7.72(d,J＝8.2Hz, 2H),7.62(s,1H),7.58(d,J＝7.9Hz,1H),7.42(t,J＝8.9Hz,3H), 7.35(t,J＝7.8Hz,1H),5.20(s,1H),4.90(s,1H),4.39(d,J＝12.5 Hz,1H),4.33(s,1H),4.22(d,J＝12.5Hz,1H),2.39(s,3H)。13C NMR (100MHz,DMSO)δ144.2,141.6,135.5,134.2,131.8,130.8,129.7,129.2, 127.5,125.6,122.0,97.9,64.4,62.9,52.2,21.1。HRMS(ESI)calcd for C18H17BrNO3S(M+H)+:406.0107,found:406.0108。
Example 17: (1R, 5S/1S,5R) -1- (3-methoxyphenyl) -4-methylene-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1, except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced by N- (2- (3-methoxyphenyl) -2-oxyethyl) -4-methylbenzenesulfonamide to give a yellow oil in 63% yield.
Yellow oil, yield 63%.1H NMR(400MHz,DMSO)δ7.72(d,J＝8.2Hz, 2H),7.41(d,J＝8.1Hz,2H),7.29(t,J＝7.8Hz,1H),6.98(d,J＝ 7.9Hz,1H),6.93(d,J＝8.2Hz,2H),5.21(s,1H),4.90(s,1H),4.37 (d,J＝12.5Hz,1H),4.26(s,1H),4.18(d,J＝12.5Hz,1H),3.74(s, 3H),2.39(s,3H)。13C NMR(100MHz,DMSO)δ159.5,144.2,141.8,134.3, 134.2,129.8,129.7,127.5,118.6,114.7,111.7,97.7,64.3,63.4,55.3, 52.5,21.1。HRMS(ESI)calcd for C19H20NO4S(M+H)+:358.1108,found:358.1109。
Example 18: (1R, 5S/1S,5R) -1- (2-methoxyphenyl) -4-methylene-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1, except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced by N- (2- (2-methoxyphenyl) -2-oxyethyl) -4-methylbenzenesulfonamide to give a white solid in 78% yield.
White solid, yield 78%.1H NMR(400MHz,DMSO)δ7.72(d,J＝8.2Hz, 2H),7.44(d,J＝8.1Hz,2H),7.40-7.34(m,1H),7.22(d,J＝6.3Hz, 1H),7.05(d,J＝8.3Hz,1H),6.94(t,J＝7.4Hz,1H),5.20(s,1H), 4.90(s,1H),4.14(s,1H),4.05(d,J＝12.0Hz,1H),3.97(d,J＝12.0 Hz,1H),3.77(s,3H),2.41(s,3H)。13C NMR(100MHz,DMSO)δ157.5, 144.3,142.0,134.1,130.6,129.8,128.5,127.4,120.9,120.4,111.2, 97.1,62.7,62.5,55.7,53.9,21.1。HRMS(ESI)calcd for C19H20NO4S(M+H)+: 358.1108,found:358.1106。
Example 19: (1R, 5S/1S,5R) -4-methylene-1- (thien-2-yl) -3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1, except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced by 4-methyl-N- (2-oxo-2- (thiophen-2-yl) ethyl) benzenesulfonamide to give a yellow oil in 81% yield.
Yellow oil, yield 81%.1H NMR(400MHz,DMSO)δ7.72(d,J＝8.3Hz, 2H),7.57(dd,J＝5.0,0.9Hz,1H),7.41(d,J＝8.1Hz,2H),7.37(dd, J＝3.5,1.0Hz,1H),7.06(dd,J＝5.0,3.7Hz,1H),5.22(s,1H),4.94 (s,1H),4.35(d,J＝12.5Hz,1H),4.31(s,1H),4.22(d,J＝12.5Hz, 1H),2.39(s,3H)。13C NMR(100MHz,DMSO)δ144.2,141.3,135.7,134.0, 129.6,127.6,127.4,126.9,98.3,65.6,61.3,52.6,21.0。HRMS(ESI)calcd for C16H16NO3S2(M+H)+:334.0566,found:334.0569。
Example 20: (1R, 5S/1S,5R) -4-methylene-1-phenethyl-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1, except that 4-methyl-N- (2-oxo-2-phenylethyl) benzenesulfonamide is replaced by 4-methyl-N- (2-oxo-4-phenylbutyl) benzenesulfonamide to give a white oil in 94% yield.
White oil, yield 94%.1H NMR(400MHz,DMSO)δ7.64(d,J＝8.2Hz, 2H),7.41(d,J＝8.1Hz,2H),7.27(t,J＝7.4Hz,2H),7.18(t,J＝ 6.5Hz,3H),5.10(s,1H),4.78(s,1H),3.80(s,1H),3.75(d,J＝3.0 Hz,2H),2.59(t,J＝7.7Hz,2H),2.40(s,3H),2.15–1.98(m,2H)。 13C NMR(100MHz,DMSO)δ144.0,142.2,140.8,134.2,129.6,128.3,128.2, 127.2,126.0,96.7,63.4,60.9,53.1,30.3,30.2,21.0。HRMS(ESI)calcd for C20H22NO3S(M+H)+:356.1315,found:356.1316。
Example 21: (1R, 5S/1S,5R) -4-ethylidene-1-phenyl-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1 except that dimethyl (prop-2-yn-1-yl) sulfonium bromide is replaced by but-2-yn-1-yl dimethylsulfonium bromide to give a white oil in 92% yield.
White oil, yield 92%.1H NMR(400MHz,DMSO)δ7.64(d,J＝8.3Hz, 2H),7.41–7.33(m,7H),5.92(q,J＝7.2Hz,1H),4.48(s,1H),4.27 (d,J＝12.8Hz,1H),4.16–4.08(m,1H),2.38(s,3H),1.81(d,J＝ 7.3Hz,3H)。13C NMR(100MHz,DMSO)δ143.9,135.4,134.6,133.1,129.6, 128.8,128.6,127.6,126.5,112.6,63.7,60.5,51.8,21.1,13.2。HRMS (ESI)calcd for C19H20NO3S(M+H)+:342.1158,found:342.1160。
Example 22: (1R, 5S/1S,5R) -4-benzylidene-1-phenyl-3-tosyl-6-oxa-3-azabicyclo [3.1.0] hexane
The procedure is as in example 1 except that dimethyl (prop-2-yn-1-yl) sulfonium bromide is replaced by 3-phenylprop-2-yn-1-yl dimethyl sulfonium bromide to give a yellow solid in 91% yield.
Yellow solid, yield 91%.1H NMR(400MHz,DMSO)δ7.71(d,J＝8.2Hz, 2H),7.44-7.38(m,4H),7.38-7.30(m,7H),7.28(t,J＝7.0Hz,1H),7.03 (s,1H),4.40(d,J＝13.1Hz,1H),4.26(d,J＝12.4Hz,2H),2.39(s, 3H)。13C NMR(100MHz,DMSO)δ144.2,136.7,135.1,134.3,132.6,129.7, 128.9,128.8,128.5,128.3,127.5,127.3,126.6,117.3,64.8,62.2,51.6, 21.2。HRMS(ESI)calcd for C24H22NO3S(M+H)+:404.1315,found:404.1314。
Other embodiments of the present application will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure disclosed herein. This application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the application and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the application being indicated by the following claims.
It will be understood that the present application is not limited to the precise arrangements that have been described above and that various modifications and changes may be made without departing from the scope thereof. The scope of the application is limited only by the appended claims.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100168093A1 (en) * | 2006-04-28 | 2010-07-01 | Miguel Angel Pericas-Brondo | Substituted 3-amino-4 -hydroxy pyrrolidines compounds, their preparation and use as medicaments |
| US20160222030A1 (en) * | 2013-10-15 | 2016-08-04 | Takeda Pharmaceutical Company Limited | Cyclopentylbenzamide Derivatives and their Use for the Treatment of Psychotic and Cognitive Disorders |
| CN109790116A (en) * | 2016-09-20 | 2019-05-21 | 葛兰素史密斯克莱知识产权（第2 号）有限公司 | TRPV4 antagonist |
| CN110256383A (en) * | 2019-06-25 | 2019-09-20 | 浙江大学城市学院 | Dibenzofurans acrylic ester compound and preparation method thereof |
-
2020
- 2020-11-23 CN CN202011321553.9A patent/CN112500419A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100168093A1 (en) * | 2006-04-28 | 2010-07-01 | Miguel Angel Pericas-Brondo | Substituted 3-amino-4 -hydroxy pyrrolidines compounds, their preparation and use as medicaments |
| US20160222030A1 (en) * | 2013-10-15 | 2016-08-04 | Takeda Pharmaceutical Company Limited | Cyclopentylbenzamide Derivatives and their Use for the Treatment of Psychotic and Cognitive Disorders |
| CN109790116A (en) * | 2016-09-20 | 2019-05-21 | 葛兰素史密斯克莱知识产权（第2 号）有限公司 | TRPV4 antagonist |
| CN110256383A (en) * | 2019-06-25 | 2019-09-20 | 浙江大学城市学院 | Dibenzofurans acrylic ester compound and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| AMAN KULSHRESTHA, ET AL.: "3,4-Dihydroxypyrrolidines via Modified Tandem Aza-Payne/Hydroamination Pathway", 《ORGANIC LETTERS》 * |
| DR. AMAN KULSHRESTHA, ET AL.: "Selectivity in the Addition Reactions of Organometallic Reagents to Aziridine-2-carboxaldehydes: The Effects of Protecting Groups and Substitution Patterns", 《CHEMISTRY - A EUROPEAN JOURNAL》 * |
| DR. HADI GHOLAMI, ET AL.: "Total Synthesis of (−)-Salinosporamide A via a Late Stage C−H Insertion", 《ANGEWANDTE CHEMIE, INTERNATIONAL EDITION》 * |
| JENNIFER M. SCHOMAKER, ET AL.: "Tetrasubstituted Pyrrolidines via a Tandem Aza-Payne/Hydroamination Reaction", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113248418A (en) * | 2021-05-11 | 2021-08-13 | 浙大城市学院 | 3-alkynyl-2, 4-diester-based pyrrole compound and preparation method thereof |
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