CN115894523A - Method for synthesizing fused nitrogen heterocycle containing 1,3 discontinuous stereo center [7,6] by stereo divergence - Google Patents
Method for synthesizing fused nitrogen heterocycle containing 1,3 discontinuous stereo center [7,6] by stereo divergence Download PDFInfo
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- 230000007935 neutral effect Effects 0.000 claims description 28
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 17
- VUAUSTRXYOQTOG-UHFFFAOYSA-N 4-ethenyl-4H-1,2-benzoxazin-3-one Chemical compound C(=C)C1C(NOC2=C1C=CC=C2)=O VUAUSTRXYOQTOG-UHFFFAOYSA-N 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 229940124530 sulfonamide Drugs 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 150000003456 sulfonamides Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 238000012986 modification Methods 0.000 abstract description 5
- 230000004048 modification Effects 0.000 abstract description 5
- 238000006243 chemical reaction Methods 0.000 description 71
- 238000002360 preparation method Methods 0.000 description 26
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 24
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- 229910052751 metal Inorganic materials 0.000 description 11
- 239000002184 metal Substances 0.000 description 11
- GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 description 10
- JVTRZJXFAOQMRA-UHFFFAOYSA-N 1,3-oxazin-2-one Chemical compound O=C1N=CC=CO1 JVTRZJXFAOQMRA-UHFFFAOYSA-N 0.000 description 8
- 239000006260 foam Substances 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
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- -1 sulfanilamide compound Chemical class 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
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- NYERMPLPURRVGM-UHFFFAOYSA-N thiazepine Chemical compound S1C=CC=CC=N1 NYERMPLPURRVGM-UHFFFAOYSA-N 0.000 description 3
- JGSIAOZAXBWRFO-UHFFFAOYSA-N 3-methylsulfanyl-1-phenyl-4,5-dihydrobenzo[g]indazole Chemical compound C1CC2=CC=CC=C2C2=C1C(SC)=NN2C1=CC=CC=C1 JGSIAOZAXBWRFO-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 1
- WOJZDKCQKJCDAV-UHFFFAOYSA-N 3-ethenyl-2H-1,2-benzoxazine Chemical class C(=C)C=1NOC2=C(C1)C=CC=C2 WOJZDKCQKJCDAV-UHFFFAOYSA-N 0.000 description 1
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- 229940125759 BACE1 protease inhibitor Drugs 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000030595 Glucokinase Human genes 0.000 description 1
- 108010021582 Glucokinase Proteins 0.000 description 1
- 108010016183 Human immunodeficiency virus 1 p16 protease Proteins 0.000 description 1
- RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 description 1
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- KHBQMWCZKVMBLN-IDEBNGHGSA-N benzenesulfonamide Chemical group NS(=O)(=O)[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 KHBQMWCZKVMBLN-IDEBNGHGSA-N 0.000 description 1
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- RPZAAFUKDPKTKP-UHFFFAOYSA-N n-(methoxymethyl)-1-phenyl-n-(trimethylsilylmethyl)methanamine Chemical compound COCN(C[Si](C)(C)C)CC1=CC=CC=C1 RPZAAFUKDPKTKP-UHFFFAOYSA-N 0.000 description 1
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
The invention discloses a method for synthesizing nitrogen heterocycles fused with 1,3 discontinuous stereocenter [7,6] by stereospecific synthesis, which relates to the technical field of organic synthesis. The invention realizes the three-dimensional divergent synthesis by changing the solvent, has excellent diastereoselectivity, realizes the new functional modification of the seven-membered benzsulfamide ring, and constructs a series of seven-membered benzsulfamide fused quinazoline heterocyclic derivatives.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing fused azacyclo containing 1,3 discontinuous stereocenter [7,6] by stereo divergence.
Background
Small organic molecules containing heterocycles have a variety of therapeutic effects. Statistically, more than 85% of biologically active compounds are composed of one or more heterocycles, which, because of their abundance in nature, have been widely used in the design of pharmaceutically active molecules that interact with various targets.
Among the heterocyclic compounds, the seven-membered benzsulfamide compound, as an important sulfanilamide compound, becomes an extremely thick pharmacophore in pharmaceutical chemistry due to its remarkable biological activity. They show great potential in various drug therapies, for example, BACE-1 inhibitors for treating Alzheimer's disease, HIV-1 protease inhibitors, and have glucokinase activity, in vitro calcium mimicking activity, antidepressant activity, and the like. From the quantitative structure-activity relationship in drug discovery, it can be easily concluded that the construction and functionalization of the heptameric benzenesulfonamide ring is crucial for biological activity. To address this problem, researchers have developed several methods to functionally modify the heptad-benzenesulfonamide ring. However, the strategies reported so far are mainly based on the construction of carbon-carbon bonds and carbon-phosphorus bonds of cyclic imine building blocks. Transition metal-catalyzed cyclization has become an effective method for constructing fused heterocyclic frameworks with multiple stereocenters. The transition metal zwitterion pi-allyl intermediate is of great interest because it has highly tunable stereoselectivity and can be constructed in one step to contain two or more stereocenters. However, few literature methods have been described to functionally modify the hepta-benzenesulfonamide ring by cyclization based on an intra-cyclic imine. This research area has been reported as an example, and unfortunately this example only achieved the construction of a [7,5] fusion loop. In 2021, chen group constructed polycyclic sulfonamide derivatives containing a stereocenter by cyclization reaction of N- (methoxymethyl) -N- (trimethylsilylmethyl) -benzylamine based on a seven-membered benzosulfonamide cyclic imine building block and an active methyleneacylimine generated in situ in the presence of trifluoroacetic acid, but no control of stereoselectivity was achieved in this example. Therefore, the development of more efficient and practical reactions to obtain fused heterocycles with multiple stereocenters, particularly 1,3 discontinuous stereocenters, is highly desirable and a great challenge in organic synthesis.
Disclosure of Invention
In order to break through the limitation of the existing reaction system on the functional modification of the heptatomic benzsulfamide, the invention realizes the high-efficiency three-dimensional divergent synthesis of the heptatomic benzsulfamide fused quinazoline heterocyclic derivative under the regulation and control of the same achiral ligand; by simply changing the solvent stereoselectivity, a pair of diastereoisomers containing 1,3 discontinuous stereocenter [7,6] fused heterocycle is obtained.
In order to achieve the purpose, the invention provides the following scheme:
the invention provides a method for synthesizing fused nitrogen heterocycles containing 1,3 discontinuous stereocenter [7,6] by stereospecific synthesis, which comprises the steps of adding [ tris (dibenzylideneacetone) ] dipalladium and a ligand into a solvent under the nitrogen atmosphere, stirring for 30 minutes at room temperature, then sequentially adding dibenzo hepta sulfonamide and vinyl benzoxazinone, heating to 70 ℃, heating and stirring for 12 hours, and then separating and purifying by neutral alumina to obtain a pair of diastereoisomers 3 and 4.
Preferably, the method for synthesizing the fused nitrogen heterocycle containing 1,3 discontinuous stereocenter [7,6] by stereo divergence comprises the following synthetic route:
the method specifically comprises the following steps: [ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by weight), a ligand (0.04mmol, 20% by weight) and a solvent (acetonitrile, 2.0mL, 0.1M) or (1,4 dioxane, 20mL, 0.01M) were added to a 10mL reaction tube or a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then dibenzoheptasulfonamide 1 (0.2mmol, 1.0equiv.) and vinylbenzoxazinone 2 (0.3mmol, 1.5uiv.) were added to the reaction system in this order, and a metal reaction bath or an oil bath was heated to 70 ℃ under a nitrogen atmosphere, heated and stirred for 12 hours, and then separated and purified by neutral alumina to obtain a pair of diastereomer 3 and diastereomer 4.
Preferably, when diastereomer 3 is prepared, the following steps are included: [ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), a ligand (0.04mmol, 20% mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a nitrogen atmosphere in a glove box, and stirred at room temperature for 30 minutes, then dibenzoheptanesulfonamide 1 (0.2mmol, 1.0equiv.) and vinylbenzoxazinone 2 (0.3mmol, 1.5equiv.) were added to the reaction system in this order, and the temperature of the metal reaction bath was raised to 70 ℃, and heated under a nitrogen atmosphere, stirred for 12 hours, and then separated and purified by neutral alumina to obtain diastereomer 3.
Preferably, when diastereomer 4 is prepared, the following steps are included: [ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by weight), a ligand (0.04mmol, 20% by weight) and 1,4-dioxane (20mL, 0.01M) were charged into a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, then dibenzoheptasulfonamide 1 (0.2mmol, 1.0equiv.) and vinylbenzoxazinone 2 (0.3mmol, 1.5equiv.) were sequentially charged into the reaction system, the temperature of the oil bath was raised to 70 ℃, heated and stirred under a nitrogen atmosphere for 12 hours, and then separated and purified by neutral alumina to obtain diastereomer 4.
Preferably, the molar ratio of [ tris (dibenzylideneacetone) ] dipalladium, ligand, dibenzoheptanesulfonamide and vinylbenzoxazinone is 1:4:20:30.
preferably, the ligand has the formula:
preferably, the dibenzoheptanesulfonamide has the following structural formula:
wherein R is 1 Selected from H, halogen or methyl, R 2 Selected from H, meS, -OCF 3 Halogen, ph or MeO.
Preferably, the dibenzo-heptad sulfonamide includes dibenzo [ d, f ] [1,2] thiazole-ne 5,5-dioxide, 9-methoxy dibenzo [ d, f ] [1,2] thiazole-ne 5,5-dioxide, 10-phenyl dibenzo [ d, f ] [1,2] thiazole-ne 5,5-dioxide, 9-fluoro dibenzo [ d, f ] [1,2] thiazole-ne 5,5-dioxide, 10- (trifluoromethoxy) dibenzo [ d, f ] [1,2] thiazole-ne 5,5-dioxide, 10- (methylthio) dibenzo [ d, f ] [1,2] thiazole-ne 5,5-dioxide, 2-methyl dibenzo [ d, f ] [ 56xft 3523 ] thiazole-ne 355723 ] thiazole-ne 5362 zxft 56, 6256 zxft [ d ] [ 3238 ] thiazole-ne [ d ] [ 325749 ] dibenzo ] thiazole-ne 3246-ne-dioxide, 345749.
Preferably, the structural formula of the vinylbenzoxazinone is as follows:
wherein R is selected from H, halogen, -CH 3 Or Me.
Preferably, the vinyl benzoxazinones include 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one, 6-chloro-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one, 7-chloro-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one, 6-fluoro-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one, 6-methyl-4-vinyl-1,4-dihydro-2H-benzo [ d ] [ 64 zxft 3264 ] oxazin-2-one or 7-methyl-4-vinyl-1,4-3434 ] oxazin-2-one.
Preferably, the solvent is acetonitrile or 1,4 dioxane.
The invention discloses the following technical effects:
the invention synthesizes a series of seven-membered benzosulfonamide fused quinazoline heterocyclic derivatives with 1,3 discontinuous stereo center in high yield based on palladium-catalyzed cyclization reaction of seven-membered benzosulfonamide cyclic imine structural units and vinyl benzoxazine compounds [4+2], realizes control of solvent on diastereoselectivity, realizes stereo-divergent synthesis by changing solvent, has excellent diastereoselectivity, realizes new functional modification of seven-membered benzosulfonamide rings, and constructs a series of seven-membered benzosulfonamide fused quinazoline heterocyclic derivatives.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings without creative efforts.
Fig. 1 shows a model of the sticks of 3a and 4a synthesized in example 1.
Detailed Description
Reference will now be made in detail to various exemplary embodiments of the invention, the detailed description should not be construed as limiting the invention but as a more detailed description of certain aspects, features and embodiments of the invention.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Further, for numerical ranges in this disclosure, it is understood that each intervening value, between the upper and lower limit of that range, is also specifically disclosed. Every intervening value, to the extent any stated value or intervening value in a stated range, and any other stated or intervening value in a stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference herein for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the present disclosure without departing from the scope or spirit of the disclosure. Other embodiments will be apparent to those skilled in the art from consideration of the specification. The description and examples are intended to be illustrative only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are open-ended terms that mean including, but not limited to.
The room temperature in the present invention means 25. + -. 2 ℃.
The invention is further illustrated by the following examples, but is not thereby to be limited in scope by the examples, each of which contains a pair of diastereomers.
Example 1
Preparation of 11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), ligand (0.04mmol, 20% mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a glove box nitrogen atmosphere and stirred at room temperature for 30 minutes, and then dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 a) (0.2mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.3mmol, 1.5equiv.) were added in sequence to the reaction system, and the metal reaction bath was warmed to 70 ℃ under nitrogen, heated and stirred for 12 hours, followed by separation and purification with neutral alumina to obtain diastereomer 3a,3a as a white solid, yield 99%, diastereomer ratio > 20%.
Preparation of 11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5
[ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), ligand (0.04mmol, 20% mmol) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then dibenzo [ d, f ] [1,2] thiazole Flat 5,5-dioxide (1 a) (0.2mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazine-2-one (2 a) (0.3mmol, 1.5equiv.) (2 a), heated to 70 ℃ under nitrogen atmosphere, stirred for 12 hours, and then separated and purified by neutral alumina to obtain diastereomer a, 89 a as a white solid, yield > 20%, diastereomer ratio > 1% 20%.
The stick models of 3a and 4a synthesized in example 1 are shown in fig. 1.
Example 2
Preparation of 2-methoxy-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, [ 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 3 b)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by mmol), a ligand (0.04mmol, 20% by mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a glove box nitrogen atmosphere and stirred at room temperature for 30 minutes, then 9-methoxydibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 b) (0.2mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.2mmol, 1.5equiv.) were added in this order to the reaction system, the temperature of the metal reaction bath was raised to 70 ℃, and under nitrogen atmosphere, stirring was heated for 12 hours, followed by separation and purification by neutral alumina to obtain diastereomer b, a solid in a pale yellow foam with a yield of > 1% diastereomer ratio.
Preparation of 2-methoxy-11-vinyl-16, 16a-dihydro-11H-dibenzo [4, 5] [ 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 4 b)
[ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), ligand (0.04mmol, 20% mmol) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then 9-methoxydibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 b) (0.2mmol, 1.0v.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.3uv, 1.5equiv.) were added in this order to the reaction system, heated to 70 ℃ under a glove box nitrogen atmosphere, stirred for 12 hours, and after separation and purification of diastereomer 4b, 81 b as a light yellow solid in a proportion of > 20%, 1.5equiv.
Example 3
Preparation of 3-phenyl-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, 6,7] [1,2] thiazolepende [3,2-b ] quinazoline 9,9-dioxide (diastereomer 3 c)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by mmol), a ligand (0.04mmol, 20% by mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a glove box nitrogen atmosphere and stirred at room temperature for 30 minutes, then 10-phenyldibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 c) (0.2mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.2mmol, 1.5equiv.) were added in this order to the reaction system, the temperature of the metal reaction bath was raised to 70 ℃, and under nitrogen atmosphere, stirring was heated for 12 hours, followed by separation and purification by neutral alumina to obtain diastereomer as a foamy solid, yield of 3c, 98%, diastereomer ratio > 20.
Preparation of 3-phenyl-11-vinyl-16, 16a-dihydro-11H-dibenzo [4, 5] [ 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 4 c)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by weight), a ligand (0.04mmol, 20% by weight) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then 10-phenyldibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 c) (0.2mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.3equ, 1.5equiv.) were added to the reaction system in this order, heated to 70 ℃, stirred under nitrogen atmosphere for 12 hours, and after separation and purification by neutral alumina, diastereomer was obtained in a solid yield of 3277% as a light yellow foam, 20% by weight.
Example 4
Preparation of 2-fluoro-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, 6,7] [1,2] thiazolepende [3,2-b ] quinazoline 9,9-dioxide (diastereomer 3 d)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by mol), a ligand (0.04mmol, 20% by mol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a glove box nitrogen atmosphere and stirred at room temperature for 30 minutes, and then 9-fluorodibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 d) (0.2mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.2mmol, 1.5equiv.) were added in this order to the reaction system, and the metal reaction bath was heated to 70 ℃ under nitrogen atmosphere, stirred under heating for 12 hours, and then separated and purified by neutral alumina to obtain diastereomer as a solid in a pale yellow foam with a yield of 3d of > 1%, 97%, diastereomer ratio.
Preparation of 2-fluoro-11-vinyl-16, 16a-dihydro-11H-dibenzo [4, 5] [ 6,7] [1,2] thiazepine [3,2-b ] quinazoline 9,9-dioxide (diastereomer 4 d)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by weight), a ligand (0.04mmol, 20% by weight) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then 9-fluorodibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 d) (0.2mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.3equ, 1.5equiv.) were sequentially added to the reaction system, the temperature was raised to 70 ℃, stirred under nitrogen atmosphere for 12 hours, and after separation and purification by neutral alumina, diastereomer was obtained in a solid yield of 3277% as a light yellow foam, with a ratio of > 20%.
Example 5
Preparation of 3- (trifluoromethoxy) -11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 3 e)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), a ligand (0.04mmol, 20% mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a glove box nitrogen atmosphere and stirred at room temperature for 30 minutes, then 10- (trifluoromethoxy) dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 e) (0.2mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.3mmol, 1.5equiv.) were added in sequence to the reaction system, the temperature was raised to 70 ℃ under a nitrogen atmosphere, stirring was heated for 12 hours, and after separation and purification by neutral alumina, diastereomer was obtained, the yield was 3e as a foamy solid, and the diastereomer ratio was > 1%, 20.
Preparation of 3- (trifluoromethoxy) -11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 4 e)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by weight), a ligand (0.04mmol, 20% by weight) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then 10- (trifluoromethoxy) dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 e) (0.2mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazine-2-one (2 a) (0.3equ, 1.5equiv.) were sequentially added to the reaction system, the temperature was raised to 70 ℃, stirred under nitrogen atmosphere with heating for 12 hours, and after purification by neutral alumina, diastereomer 32e was obtained in a pale yellow solid yield of > 1%, 4v%.
Example 6
Preparation of 3- (methylthio) -11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 3 f)
[ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), ligand (0.04mmol, 20% mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a nitrogen atmosphere in a glove box, and stirred at room temperature for 30 minutes, and then 10- (methylthio) dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 f) (0.2 mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one 3a (2 a) (0.2 mmol, 1.5equiv.) were added in this order to the reaction system, and the temperature was raised to 70 ℃ under a nitrogen atmosphere, heated and stirred for 12 hours, followed by separation and purification with neutral alumina to obtain the diastereomer 3f in a foamy solid with a yield of 95%, a diastereomer ratio of > 20%.
Preparation of 3- (methylthio) -11-vinyl-16, 16a-dihydro-11H-dibenzo [4, 5] [ 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 4 f)
[ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), ligand (0.04mmol, 20% mmol) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then 10- (methylthio) dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 f) (0.2mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.34uieq, 1.5uieq) were added to the reaction system in this order, heated to 70 ℃ under an oil bath, stirred under heating for 12 hours under nitrogen atmosphere, and after separation by neutral alumina, diastereomer was obtained as a diastereomer in a solid yield of > 20% in a proportion, 1.4equiv.
Example 7
Preparation of 6-methyl-11-vinyl-16, 16a-dihydro-11H-dibenzo [4, 5] [ 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 3 g)
[ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), a ligand (0.04mmol, 20% mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a nitrogen atmosphere in a glove box and stirred at room temperature for 30 minutes, and then 2-methyldibenzo [ d, f ] [1,2] thiazole Flat 5,5-dioxide (1 g) (0.2 mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.20 mmol, 1.5equiv.) were added to the reaction system in this order, and the temperature was raised to 70 ℃ under a nitrogen atmosphere, heated and stirred for 12 hours, followed by separation and purification with neutral alumina to obtain a diastereomer in the form of a foamy solid in a yield of 96%, a diastereomer ratio of > 1% 20%.
Preparation of 6-methyl-11-vinyl-16, 16a-dihydro-11H-dibenzo [4, 5] [ 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 4 g)
[ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), ligand (0.04mmol, 20% mmol) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then 2-methyldibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 g) (0.2 mmol, 1.0v.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.3uv, 1.5equiv.) were added in this order to the reaction system, heated to 70 ℃ under a glove box nitrogen atmosphere, stirred for 12 hours, and after separation and purification of diastereomer as a pale yellow solid, 83 g, 20% in a proportion of > 20%, 4% yield by neutral alumina.
Example 8
Preparation of 6-fluoro-11-vinyl-16, 16a-dihydro-11H-dibenzo [4, 5] [ 6,7] [1,2] thiazepine [3,2-b ] quinazoline 9,9-dioxide (diastereomer 3H)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by mmol), a ligand (0.04mmol, 20% by mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a glove box nitrogen atmosphere and stirred at room temperature for 30 minutes, and then 2-fluorodibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1H) (0.2mmol, 1.0equiv.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.2mmol, 1.5equiv.) were added in this order to the reaction system, and the metal reaction bath was warmed to 70 ℃ under nitrogen atmosphere, heated and stirred for 12 hours, followed by separation and purification with neutral alumina to obtain diastereomer as a foamy solid in a yield of 3H, 97%, diastereomer ratio > 20.
6-fluoro-11-vinyl-16, 16a-dihydro-11H-dibenzo [4, 5] [ 6,7] [1,2] thiazepine [3,2-b ] quinazoline 9,9-dioxide
Preparation of (diastereomer 4 h)
[ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), ligand (0.04mmol, 20% mmol) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then 2-fluorodibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1H) (0.2 mmol, 1.0v.) and 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 a) (0.3uv, 1.5equiv.) were added in this order to the reaction system, heated to 70 ℃ under a glove box nitrogen atmosphere, stirred for 12 hours, and after separation and purification by neutral alumina, the diastereomer was obtained as a pale yellow solid in a yield of 79%, with a proportion of > 1.5equiv.
Example 9
13-chloro-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, [ 6,7] [1,2] thiazolependen [3,2-b ] quinazoline 9,9-dioxide
Preparation of (diastereomer 3 i)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by mmol), a ligand (0.04mmol, 20% by mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a glove box nitrogen atmosphere and stirred at room temperature for 30 minutes, then dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 a) (0.2mmol, 1.0equiv.) and 6-chloro-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 i) (0.2mmol, 1.5equiv.) were added in sequence to the reaction system, the metal reaction bath was warmed to 70 ℃ under nitrogen atmosphere, stirred under heating for 12 hours, and then separated and purified by neutral alumina to obtain diastereomer 3i, yield: 98% diastereomeric ratio > 20.
Preparation of 13-chloro-11-vinyl-16, 16a-dihydro-11H-dibenzo [4, 5] [ 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 4 i)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by weight), a ligand (0.04mmol, 20% by weight) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 a) (0.2mmol, 1.0equiv.) and 6-chloro-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 i) (0.3equiv., 1) were sequentially added to the reaction system, the temperature was raised to 70 ℃, stirred under nitrogen atmosphere for 12 hours, and after separation by neutral alumina, diastereomer was obtained, which was purified as a light yellow solid, yielding 3273% by weight, and a light-yellow solid ratio of > 20% in an oil bath.
Example 10
14-chloro-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, [ 6,7] [1,2] thiazolependen [3,2-b ] quinazoline 9,9-dioxide
Preparation of (diastereomer 3 j)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by mmol), a ligand (0.04mmol, 20% by mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a glove box nitrogen atmosphere and stirred at room temperature for 30 minutes, then dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 a) (0.2mmol, 1.0equiv.) and 7-chloro-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 j) (0.2mmol, 1.5equiv.) were added in sequence to the reaction system, the metal reaction bath was warmed to 70 ℃ under nitrogen atmosphere, stirred under heating for 12 hours, and then separated and purified by neutral alumina to obtain the diastereomer as a foamy solid, with a yield of 3j, 98%, a diastereomer ratio of > 20.
14-chloro-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, 6,7] [1,2] thiazolepende [3,2-b ] quinazoline 9,9-dioxide
Preparation of (diastereomer 4 j)
[ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), ligand (0.04mmol, 20% mmol) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 a) (0.2mmol, 1.0equiv.) and 7-chloro-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazine-2-one (2 j) (0.33236 equiv.) -were added to the reaction system in this order, heated to 70 ℃ under an oil bath, stirred under heating for 12 hours under nitrogen atmosphere, and after that the diastereomer was isolated as a pale yellow solid, 324j, 83, 20% in a proportion, 20% diastereomeric yield.
Example 11
13-fluoro-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, [ 6,7] [1,2] thiazolependen [3,2-b ] quinazoline 9,9-dioxide
Preparation of (diastereomer 3 k)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by mmol), a ligand (0.04mmol, 20% by mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a glove box nitrogen atmosphere and stirred at room temperature for 30 minutes, then dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 a) (0.2mmol, 1.0equiv.) and 6-fluoro-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 k) (0.3mmol, 1.5equiv.) were added in sequence to the reaction system, the metal reaction bath was warmed to 70 ℃ under nitrogen atmosphere, stirred under heating for 12 hours, and then separated and purified by neutral alumina to obtain the diastereomer 3k, yield: 99% diastereomeric ratio, > 20%, 3 k.
13-fluoro-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, [ 6,7] [1,2] thiazolependen [3,2-b ] quinazoline 9,9-dioxide
Preparation of (diastereomer 4 k)
[ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), ligand (0.04mmol, 20% mmol) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 a) (0.2mmol, 1.0equiv.) and 6-fluoro-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 k) (0.3Uv, 1.5equiv.) were added in this order to the reaction system, heated to 70 ℃ under an oil bath, stirred under heating for 12 hours under nitrogen atmosphere, followed by separation of the diastereomer enantiomer k, 83 k, 20% diastereomer, 1% in a ratio, 20 mmol, and 20% yield as a light yellow solid.
Example 12
Preparation of 13-methyl-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, [ 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 3 l)
[ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), ligand (0.04mmol, 20% mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a nitrogen atmosphere in a glove box and stirred at room temperature for 30 minutes, then dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 a) (0.2 mmol, 1.0equiv.) and 6-methyl-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one 3l (2 l) (0.20 mmol, 1.5equiv.) were added in this order to the reaction system, the temperature was raised to 70 ℃ under a nitrogen atmosphere, heated and stirred for 12 hours, after which the diastereomer was isolated and purified by neutral alumina to obtain a 3l, a yield of 91%, a diastereomer in the form of a pale yellow foam, with a proportion of > 1.20%.
Preparation of (11R, 16aS) -13-methyl-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 4 l)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by weight), a ligand (0.04mmol, 20% by weight) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 a) (0.2mmol, 1.0equiv.) and 6-methyl-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazine-2-one (2 l) (0.3equiv., 1) were sequentially added to the reaction system, the temperature was raised to 70 ℃, stirred under heating under nitrogen atmosphere for 12 hours, and after separation by neutral alumina, diastereomer was obtained in a solid yield of 324l, which was 83% by weight, and a light yellow solid ratio.
Example 13
Preparation of 14-methyl-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, [ 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 3 m)
[ tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% by mmol), a ligand (0.04mmol, 20% by mmol) and acetonitrile (2.0mL, 0.1M) were added to a 10mL reaction tube under a glove box nitrogen atmosphere and stirred at room temperature for 30 minutes, then dibenzo [ d, f ] [1,2] thiazole flat 5,5-dioxide (1 a) (0.2mmol, 1.0equiv.) and 7-methyl-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one (2 m) (0.2mmol, 1.5equiv.) were added in sequence to the reaction system, the metal reaction bath was warmed to 70 ℃ under nitrogen atmosphere, stirred under heating for 12 hours, and then separated and purified by neutral alumina to obtain the diastereomer 3m, yield of 3m was > 3% diastereomeric ratio.
Preparation of 14-methyl-11-vinyl-16, 16a-dihydro-11H-dibenzo [4,5, [ 6,7] [1,2] thiazoleppin [3,2-b ] quinazoline 9,9-dioxide (diastereomer 4 m)
[ Tris (dibenzylideneacetone) ] dipalladium (0.01mmol, 5% mmol), ligand (0.04mmol, 20% mmol) and 1,4-dioxane (20mL, 0.01M) were added to a 120mL reaction tube under a glove box nitrogen atmosphere, stirred at room temperature for 30 minutes, and then dibenzo [ d, f ] [1,2] thiazole Flat 5,5-dioxide (1 a) (0.2mmol, 1.0equiv.) and 7-methyl-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazine-2-one (2 m) (0.34m, 1.5uiv.) were added in this order to the reaction system, the temperature was raised to 70 ℃, stirred under heating under nitrogen atmosphere for 12 hours, and after separation of diastereomer m as a pale yellow solid with > 83, 20% yield by neutral alumina, 4m, 1.5equiv.
The above-described embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solutions of the present invention can be made by those skilled in the art without departing from the spirit of the present invention, and the technical solutions of the present invention are within the scope of the present invention defined by the claims.
Claims (8)
1. A method for synthesizing nitrogen heterocycles fused with 1,3 discontinuous stereocenter [7,6] by stereospecific synthesis is characterized in that [ tris (dibenzylideneacetone) ] dipalladium and ligand are added into a solvent under nitrogen atmosphere, stirred for 30 minutes at room temperature, then dibenzo hepta-sulfonamide and vinyl benzoxazinone are sequentially added, the temperature is raised to 70 ℃, heated and stirred for 12 hours, and then separated and purified by neutral alumina to obtain a pair of diastereoisomer 3 and diastereoisomer 4.
2. The method for stereoscopically synthesizing the fused nitrogen heterocycle containing 1,3 discontinuous stereocenter [7,6] according to claim 1, wherein the molar ratio of [ tris (dibenzylideneacetone) ] dipalladium, ligand, dibenzoheptanesulfonamide and vinyl benzoxazinone is 1:4:20:30.
3. the method of claim 2, wherein the stereo divergent synthesis comprises 1,3 discontinuous stereo center [7,6]A method for fusing nitrogen heterocycles, characterized in that the ligand has the following structural formula:
4. the stereoscopic divergence synthesis of claim 2 comprising 1,3 discontinuous stereoscopic centers [7,6]A method of fusing nitrogen heterocycles, wherein the dibenzo-heptanesulfonamide has the following structural formula:
wherein R is 1 Selected from H, halogen or methyl, R 2 Selected from H, meS, -OCF 3 Halogen, ph or MeO.
5. The method of claim 4, wherein the dibenzo-heptad sulfonamide comprises dibenzo [ d, f ] [1,2] thiazole Flat 5,5-dioxide, 9-methoxydibenzo [ d, f ] [1,2] thiazole Flat 5,5-dioxide, 10-phenyldibenzo [ d, f ] [1,2] thiazole Flat 5,5-dioxide, 9-fluorodibenzo [ d, f ] [1,2] thiazole Flat 5,5-dioxide, 10- (trifluoromethoxy) dibenzo [ d, f ] [1,2] thiazole Flat 5,5-dioxide, 10- (methylthio) dibenzo [ d, f ] [1,2] thiazole Flat 5,5-dioxide, 2-methyldibenzo [ d, f ] [1,2] thiazole Flat 5,5-dioxide, 2-fluorodibenzo [ d, f ] [1,2] thiazole Flat 5,5-dioxide or dibenzo [ d, f ] [ 58zxft 5852 ] thiazole Flat 3575-zxft 3575-dioxide.
6. The method of claim 2, wherein the stereo divergent synthesis comprises 1,3 discontinuous stereo center [7,6]The method for fusing the nitrogen heterocycle is characterized in that the structural formula of the vinyl benzoxazinone is as follows:
wherein R is selected from H, halogen, -CH 3 Or Me.
7. The method for stereoscopically synthesizing fused nitrogen heterocycles containing 1,3 discontinuous stereocenters [7,6] according to claim 6, wherein the vinyl benzoxazinone comprises 4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one, 6-chloro-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one, 7-chloro-4-vinyl-1,4-dihydro-2H-benzo [ d ] [1,3] oxazin-2-one, 6-fluoro-4-vinyl-1,4-dihydro-2H-benzo [ d 4924 ] oxazin-2-one, 6-methyl-4-vinyl-6242-zxft 3724-dihydro-2H-benzo [ d ] [ 9843 ] oxazin-2-9843 ] or 2-methyl-benzoxazin-2-d-3-3538 ] ketone.
8. The method for synthesizing the non-continuous stereogenic center [7,6] fused azacyclic ring containing 1,3 by stereospecific synthesis according to claim 1, wherein the solvent is acetonitrile or 1,4 dioxane.
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| CN104387310A (en) * | 2014-11-12 | 2015-03-04 | 华中师范大学 | 3-vinyl indoline derivatives with optical activity and asymmetric synthesis method of same |
| CN107573285A (en) * | 2017-09-13 | 2018-01-12 | 华中师范大学 | The asymmetric syntheses of palladium chtalyst contains the quinolinones of quaternary carbon center and its new method of derivative |
| CN109400629A (en) * | 2018-12-17 | 2019-03-01 | 江西师范大学 | Indoles spirooxazine heterocycle compound and preparation method thereof |
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