CN114213431A - 螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物及其合成方法 - Google Patents
螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物及其合成方法 Download PDFInfo
- Publication number
- CN114213431A CN114213431A CN202210057833.6A CN202210057833A CN114213431A CN 114213431 A CN114213431 A CN 114213431A CN 202210057833 A CN202210057833 A CN 202210057833A CN 114213431 A CN114213431 A CN 114213431A
- Authority
- CN
- China
- Prior art keywords
- oxazine
- benzo
- compound
- spiro
- isoquinoline
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 125000005605 benzo group Chemical group 0.000 title claims abstract description 63
- 150000001875 compounds Chemical class 0.000 title claims abstract description 37
- 125000003003 spiro group Chemical group 0.000 title claims abstract description 35
- 238000010189 synthetic method Methods 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 239000000654 additive Substances 0.000 claims abstract description 9
- 230000000996 additive effect Effects 0.000 claims abstract description 8
- 229940126214 compound 3 Drugs 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 229940125782 compound 2 Drugs 0.000 claims abstract description 5
- 239000007800 oxidant agent Substances 0.000 claims abstract description 5
- 230000001590 oxidative effect Effects 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 230000002194 synthesizing effect Effects 0.000 claims description 9
- -1 2-morpholinylethyl Chemical group 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-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
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-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
- 241000551547 Dione <red algae> Species 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 229940057847 polyethylene glycol 600 Drugs 0.000 claims description 4
- QVLTVILSYOWFRM-UHFFFAOYSA-L CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C Chemical group CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C QVLTVILSYOWFRM-UHFFFAOYSA-L 0.000 claims description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 3
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- JIMXXGFJRDUSRO-UHFFFAOYSA-N adamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2CC1(C(=O)O)C3 JIMXXGFJRDUSRO-UHFFFAOYSA-N 0.000 claims description 2
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 claims description 2
- 229940125898 compound 5 Drugs 0.000 claims description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- MMAGMBCAIFVRGJ-UHFFFAOYSA-J iridium(3+);1,2,3,4,5-pentamethylcyclopenta-1,3-diene;tetrachloride Chemical compound Cl[Ir+]Cl.Cl[Ir+]Cl.CC=1C(C)=C(C)[C-](C)C=1C.CC=1C(C)=C(C)[C-](C)C=1C MMAGMBCAIFVRGJ-UHFFFAOYSA-J 0.000 claims description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 2
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 2
- 229940071536 silver acetate Drugs 0.000 claims description 2
- HSYLTRBDKXZSGS-UHFFFAOYSA-N silver;bis(trifluoromethylsulfonyl)azanide Chemical class [Ag+].FC(F)(F)S(=O)(=O)[N-]S(=O)(=O)C(F)(F)F HSYLTRBDKXZSGS-UHFFFAOYSA-N 0.000 claims description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 2
- 239000012279 sodium borohydride Substances 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- 238000001308 synthesis method Methods 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical group N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 239000012298 atmosphere Substances 0.000 abstract description 3
- FPWQRGVWEUVZSN-UHFFFAOYSA-N [N+](=[N-])=C1C(NC(C2=CC=CC=C12)=O)=O Chemical class [N+](=[N-])=C1C(NC(C2=CC=CC=C12)=O)=O FPWQRGVWEUVZSN-UHFFFAOYSA-N 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 125000004430 oxygen atom Chemical group O* 0.000 abstract description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 38
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 37
- 239000007787 solid Substances 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 238000004293 19F NMR spectroscopy Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical compound C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 2
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000009987 spinning Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- RJYMRRJVDRJMJW-UHFFFAOYSA-L dibromomanganese Chemical compound Br[Mn]Br RJYMRRJVDRJMJW-UHFFFAOYSA-L 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 238000004983 proton decoupled 13C NMR spectroscopy Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
本发明公开了一种螺[苯并[d][1,3]噁嗪‑异喹啉二酮]类化合物及其合成方法，属于有机合成技术领域。将N‑芳基脒1、重氮异喹啉二酮类化合物2、催化剂和有机溶剂混合，在氧化剂(和添加剂)存在下，升温反应制得螺[苯并[d][1,3]噁嗪‑异喹啉二酮]类化合物3。本发明中化合物3结构新颖，通过N‑芳基脒和重氮异喹啉二酮类化合物在空气氛围下的一锅串联反应，同时构建出噁嗪环和螺环，实现螺[苯并[d][1,3]噁嗪‑异喹啉二酮]类化合物的高效合成；噁嗪骨架中的氧原子来源于空气，具有经济和可持续的优点。
Description
技术领域
本发明属于有机合成技术领域，具体涉及螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物及其合成方法。
背景技术
螺环骨架广泛存在于天然产物、手性配体、临床药物和功能材料中，用途极其广泛。在众多的螺环类化合物中，含异喹啉酮结构单元的螺环衍生物往往具有显著的抗病毒、抗癌和消炎等效果，具有重要的药用价值。
此外，含有氮、氧杂原子的苯并噁嗪是一类重要的稠杂环衍生物，具有多种显著的生物活性，是新药开发的主要来源之一。同时苯并噁嗪类化合物还具有优异的光电性能，从而被广泛用于热敏和光电材料的制备等。
根据药效基团的拼合原理，包含了异喹啉酮和苯并噁嗪这两种优势结构单元的螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物可能具有更为优异的生物活性及其它性能，具有潜在的应用价值。
目前，尚未有螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的相关报道。因此，研究并开发从简单易得的原料出发，通过简便途径合成螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的高效、可持续方法，具有十分重要的理论意义和应用前景。
发明内容
本发明解决的技术问题是提供了一种螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物及其合成方法，该合成方法通过N-芳基脒和重氮异喹啉二酮类化合物之间的串联反应和独特的插氧过程而高效完成，合成方法具有原料简单易得、操作简便、条件温和、底物适用范围广等优点，具有潜在的应用价值。
本发明为解决上述技术问题采用的技术方案，提供了一种螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物，其结构通式为：
其中：R1为氢、卤素、苯基或C1-4烷基，R2为C1-4烷基或C3-6环烷基，R3为C1-4烷基、2-吗啉乙基、苄基、取代苄基、2-萘基、苯基或取代苯基，取代苄基苯环上的取代基为一元或多元取代C1-4烷基或C1-4烷氧基，取代苯基苯环上的取代基为C1-4烷基、C1-4烷氧基、卤素或三氟甲基。
本发明还提供了一种螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的合成方法，包括如下操作：将N-芳基脒1、重氮异喹啉二酮类化合物2、催化剂和有机溶剂混合，在氧化剂存在下，升温反应制得螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物3。采用反应方程式表示如下：
其中，取代基与前述螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物通式结构中描述相同。
进一步地，在上述技术方案中，所述有机溶剂为起到溶解原料的作用，优选甲醇、乙醇、乙腈、聚乙二醇-400(PEG-400)或聚乙二醇-600(PEG-600)。
进一步地，在上述技术方案中，所述催化剂为二氯(五甲基环戊二烯基)合铑(III)二聚体{简称[RhCp*Cl2]2}或二氯(五甲基环戊二烯基)合铱(III)二聚体{简称[IrCp*Cl2]2}。采用其他催化剂，例如二氯双(4-甲基异丙基苯基)钌(II){简称[Ru(p-cymene)Cl2]2}或五羰基溴化锰{简称MnBr(CO)5}等时，反应未检测到需要产物。
进一步地，在上述技术方案中，所述反应温度为40-80℃。
进一步地，在上述技术方案中，所述氧化剂为空气、氧气；优选为空气氛围下。
进一步地，在上述技术方案中，所述N-芳基脒1、重氮异喹啉二酮类化合物2与催化剂摩尔比为1-1.5:1-1.5:0.02-0.06。
进一步地，在上述技术方案中，反应中加入添加剂；添加剂选自六氟锑酸银、双三氟甲烷磺酰亚胺银盐、乙酸银、醋酸铜、醋酸铯、特戊酸、1-金刚烷甲酸、醋酸、碳酸钾或氢氧化钠。
进一步地，在上述技术方案中，所述N-芳基脒1与添加剂摩尔比为1-1.5:0.2-1。
本发明还进一步提供了所述螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的应用。
进一步地，在上述技术方案中，将螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物3在硼氢化钠存在下还原生成化合物4；对于化合物3中R1为溴代物时，在金属钯催化剂存在下与苯硼酸、苯乙烯或苯乙炔偶联生成化合物5、化合物6或化合物7。化合物4-7结构通式为：
发明有益效果：
本发明与现有技术相比具有以下优点：1)合成过程简单、高效、经济。通过N-芳基脒和重氮异喹啉二酮类化合物在空气氛围下的一锅串联反应，同时构建出噁嗪环和螺环，实现螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的高效合成；噁嗪骨架中的氧原子来源于空气，具有经济和可持续的特点。2)原料价廉易得，反应条件温和，操作简便，底物的适用范围广。
说明书附图
图1为实施例1中化合物3a的X-射线单晶衍射图。
具体实施方式
以下通过实施例对本发明的上述内容做进一步详细说明，但不应该将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例1
向15mL反应瓶中依次加入1a、有机溶剂、催化剂(和添加剂)和2a，盖上塞子密封，将其置于油浴中升温搅拌反应。待反应结束后，冷却至室温，萃取，干燥，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20/1)得白色固体产物3a。
通过改变反应催化剂(和添加剂)、有机溶剂、反应物之间当量比和反应温度等反应条件，反应结果如下：
表1不同条件下3a的合成a
实施例2
向15mL反应瓶中依次加入1a(35.2mg,0.2mmol)、聚乙二醇-600(1mL)、二氯(五甲基环戊二烯基)合铑(III)二聚体(4.9mg,0.008mmol)、醋酸(2.3μL,0.04mmol)和2a(760.4mg,0.3mmol)，盖上塞子密封，将其置于60℃油浴中搅拌反应24h。待反应结束后，冷却至室温，萃取，干燥，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20/1)得白色固体产物3a(52mg,75％)。1H NMR(400MHz,CDCl3)δ8.21(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.60(td,J1＝7.6Hz,J2＝1.6Hz,1H),7.49(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.44(d,J＝8.0Hz,1H),7.19-7.12(m,2H),6.86(td,J1＝7.6Hz,J2＝1.6Hz,1H),6.29(dd,J1＝8.0Hz,J2＝1.2Hz,1H),3.19(s,3H),1.28(s,9H).13C NMR(CDCl3,150MHz):δ171.3,166.5,163.8,139.0,137.8,134.7,130.2,129.5,128.4,127.0,126.8,126.4,125.2,124.2,123.1,79.2,37.7,27.63,27.58.HRMS calcd for C21H21N2O3:349.1547[M+H]+,found:349.1541.
实施例3
依照实施例2方法和步骤a,b，通过改变反应物1和反应物2，合成出各种螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物3a-3z和3aa-3hh。
具体结果如下：
代表性产物表征数据如下：
2-(tert-Butyl)-2',6-dimethyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3b)
White solid(52mg,72％).1H NMR(CDCl3,600MHz):δ8.32(d,J＝7.8Hz,1H),7.70(t,J＝7.8Hz,1H),7.61(t,J＝7.8Hz,1H),7.52(d,J＝8.4Hz,1H),7.17(d,J＝7.8Hz,1H),7.05(d,J＝7.8Hz,1H),6.14(s,1H),3.31(s,3H),2.11(s,3H),1.36(s,9H).13C NMR(CDCl3,100MHz):δ171.4,165.6,163.9,139.2,136.7,135.3,134.7,130.9,129.5,128.4,127.1,126.3,125.2,124.4,122.9,79.0,37.6,27.64,27.58,21.14.HRMS calcd for C22H23N2O3:363.1703[M+H]+,found:363.1703.
2-(tert-Butyl)-6-isopropyl-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3c)
White solid(57mg,73％).1H NMR(CDCl3,400MHz):δ8.32(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.70(td,J1＝8.0Hz,J2＝1.6Hz,1H),7.60(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.54(d,J＝7.6Hz,1H),7.21(d,J＝8.0Hz,1H),7.12(dd,J1＝8.0Hz,J2＝2.0Hz,1H),6.17(d,J＝2.0Hz,1H),3.30(s,3H),2.66-2.60(m,1H),1.36(s,9H),1.023(d,J＝7.2Hz,3H).1.016(d,J＝6.8Hz,3H).13C NMR(CDCl3,150MHz):δ171.4,165.7,163.9,147.8,139.1,135.7,134.7,129.5,128.3,127.8,127.0,126.4,125.2,122.8,122.2,79.2,37.6,33.6,27.61,27.59,23.8,23.7.HRMS calcd for C24H27N2O3:391.2016[M+H]+,found:391.2014.
2-(tert-Butyl)-2'-methyl-6-phenyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3d)
White solid(49mg,58％).1H NMR(CDCl3,600MHz):δ8.33(dd,J1＝8.4Hz,J2＝1.2Hz,1H),7.71(td,J1＝7.8Hz,J2＝1.2Hz,1H),7.61(td,J1＝7.8Hz,J2＝1.2Hz,1H),7.56(d,J＝7.8Hz,1H),7.49(dd,J1＝8.4Hz,J2＝1.2Hz,1H),7.36-7.32(m,3H),7.28-7.26(m,3H),6.55(d,J＝1.8Hz,1H),3.33(s,3H),1.38(s,9H).13C NMR(CDCl3,100MHz):δ171.3,166.5,163.8,139.8,139.7,138.9,137.1,134.8,129.7,128.91,128.86,128.5,127.6,127.1,126.8,126.7,125.2,123.6,122.7,79.2,37.8,27.7,27.6.HRMS calcd forC27H25N2O3:425.1860[M+H]+,found:425.1853.
2-(tert-Butyl)-6-fluoro-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3e)
White solid(48mg,66％).1H NMR(DMSO-d6,400MHz):δ8.23(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.83(td,J1＝7.6Hz,J2＝1.6Hz,1H),7.72(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.51(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.29-7.25(m,1H),7.17(td,J1＝7.6Hz,J2＝2.8Hz,1H),6.40(dd,J1＝8.8Hz,J2＝3.2Hz,1H),3.22(s,3H),1.26(s,9H).13C NMR(CDCl3,100MHz):δ170.9,165.8(d,4JC-F＝1.4Hz),163.5,160.8(d,1JC-F＝245.6Hz),138.4,134.9,134.2(d,4JC-F＝2.9Hz),129.8,128.7,128.1(d,3JC-F＝7.9Hz),127.0,125.1,124.5(d,3JC-F＝7.2Hz),117.0(d,2JC-F＝21.7Hz),111.3(d,2JC-F＝25.3Hz),78.7,37.7,27.7,27.5.19F NMR(CDCl3,376MHz):δ-113.7(td,J1＝8.3Hz,J2＝4.1Hz).HRMS calcd for C21H20FN2O3:367.1452[M+H]+,found:367.1450.
2-(tert-Butyl)-6-chloro-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3f)
White solid(49mg,64％).1H NMR(CDCl3,400MHz):δ8.25(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.66-7.62(m,1H),7.57-7.53(m,1H),7.42(d,J＝7.2Hz,1H),7.134-7.131(m,2H),6.24(s,1H),3.24(s,3H),1.27(s,9H).13C NMR(CDCl3,100MHz):δ170.8,166.8,163.5,138.3,136.6.134.9,131.8,130.4,129.9,128.7,127.8,127.1,125.1,124.7,124.2,78.6,37.8,27.7,27.5.HRMS calcd for C21H20ClN2O3:383.1157[M+H]+,found:383.1158.
6-Bromo-2-(tert-butyl)-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3g)
White solid(52mg,61％).1H NMR(CDCl3,400MHz):δ8.33(d,J＝7.6Hz,1H),7.75-7.71(m,1H),7.65-7.62(m,1H),7.50(d,J＝8.0Hz,1H),7.37(dd,J1＝8.4Hz,J2＝2.0Hz,1H),7.15(d,J＝8.4Hz,1H),6.45(d,J＝2.0Hz,1H),3.33(s,3H),1.34(s,9H).13C NMR(CDCl3,100MHz):δ170.8,166.9,163.5,138.3,137.1,134.9,133.4,129.9,128.7,128.1,127.2,127.0,125.1,119.4,78.4,37.8,27.8,27.5.HRMS calcd for C21H20BrN2O3:427.0652[M+H]+,found:427.0655.
2-(tert-Butyl)-6-iodo-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3h)
White solid(57mg,60％).1H NMR(CDCl3,400MHz):δ8.33(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.72(td,J1＝8.0Hz,J2＝1.6Hz,1H),7.63(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.57(dd,J1＝8.4Hz,J2＝2.0Hz,1H),7.49(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.02(d,J＝8.0Hz,1H),6.61(d,J＝2.0Hz,1H),3.33(s,3H),1.34(s,9H).13C NMR(CDCl3,100MHz):δ170.8,167.0,163.5,139.5,138.3,137.8,134.9,132.8,129.9,128.7,128.3,127.2,125.4,125.0,90.2,78.1,37.8,27.8,27.5.HRMS calcd for C21H20IN2O3:475.0513[M+H]+,found:475.0512.
2-(tert-Butyl)-2',7-dimethyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3i)
White solid(47mg,65％).1H NMR(CDCl3,600MHz):δ8.30(dd,J1＝7.8Hz,J2＝0.6Hz,1H),7.69(td,J1＝7.8Hz,J2＝1.8Hz,1H),7.59(td,J1＝7.8Hz,J2＝1.2Hz,1H),7.52(dd,J1＝7.8Hz,J2＝0.6Hz,1H),7.11(d,J＝0.6Hz,1H),6.77(dd,J1＝8.4Hz,J2＝1.2Hz,1H),6.26(d,J＝7.8Hz,1H),3.29(s,3H),2.26(s,3H),1.37(s,9H).13C NMR(CDCl3,150MHz):δ171.5,166.5,163.9,140.5,139.1,137.5,134.7,129.4,128.3,127.5,127.0,126.9,125.2,124.0,120.3,79.2,37.7,27.6,21.0.HRMS calcd for C22H23N2O3:363.1703[M+H]+,found:363.1702.
2-(tert-Butyl)-7-chloro-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3j)
White solid(49mg,64％).1H NMR(CDCl3,400MHz):δ8.31(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.71(td,J1＝7.6Hz,J2＝1.6Hz,1H),7.61(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.52-7.50(m,1H),7.28(d,J＝2.0Hz,1H),6.93(dd,J1＝8.4Hz,J2＝2.0Hz,1H),6.30(d,J＝8.4Hz,1H),3.30(s,3H),1.36(s,9H).13C NMR(CDCl3,100MHz):δ170.9,167.7,163.6,139.3,138.4,135.9,134.8,129.8,128.6,126.9,126.7,126.4,125.4,125.2,121.6,78.9,37.9,27.7,27.5.HRMS calcd for C21H20ClN2O3:383.1157[M+H]+,found:383.1158.
2-(tert-Butyl)-8-methyl-4-phenyl-5-(propan-2-ylidene)-5H-benzo[d][1,3]diazepine(3k)White solid(50mg,59％).1H NMR(CDCl3,600MHz):δ8.31(d,J＝7.8Hz,1H),7.72-7.70(m,1H),7.62(t,J＝7.8Hz,1H),7.50(d,J＝7.8Hz,1H),7.45(d,J＝1.8Hz,1H),7.08(dd,J1＝8.4Hz,J2＝1.8Hz,1H),6.24(d,J＝8.4Hz,1H),3.30(s,3H),1.36(s,9H).13C NMR(CDCl3,100MHz):δ170.9,167.8,163.6,139.4,138.4,134.9,129.8,129.6,129.4,128.6,126.9,125.6,125.2,123.9,122.1,79.0,37.9,27.7,27.5.HRMS calcd forC21H20BrN2O3:427.0652[M+H]+,found:427.0649.
2-(tert-Butyl)-5-fluoro-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3l)
White solid(23mg,31％).1H NMR(DMSO-d6,400MHz):δ8.19(dd,J1＝8.0Hz,J2＝1.6Hz,1H),7.79(td,J1＝7.6Hz,J2＝1.6Hz,1H),7.69(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.44-7.39(m,J＝7.6Hz,2H),7.14(d,J＝7.6Hz,1H),6.98-6.94(m,1H),3.30(s,3H),1.18(s.9H).13C NMR(CDCl3,100MHz):δ169.7,165.4,163.4,157.7(d,1JC-F＝247.0Hz),139.5,139.0,134.3,131.0(d,3JC-F＝10.1Hz),129.8,128.5,127.5,124.3(d,3JC-F＝2.9Hz),122.1(d,4JC-F＝2.9Hz),113.9(d,2JC-F＝21.0Hz),111.0(d,2JC-F＝12.2Hz),75.1,37.6,27.5,27.3.19F NMR(CDCl3,376MHz):δ-115.7(dd,J1＝9.8Hz,J2＝5.6Hz).HRMS calcd forC21H20FN2O3 367.1452[M+H]+,found:367.1451.
2-(tert-Butyl)-8-fluoro-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3m)
White solid(42mg,57％).1H NMR(DMSO-d6,400MHz):δ8.22(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.83(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.72(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.57(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.24-7.19(m,1H),7.09-7.05(m,1H),6.31(d,J＝7.6Hz,1H),3.18(s,3H),1.29(s,9H).13C NMR(CDCl3,150MHz):δ170.8,167.1,163.6,156.5(d,1JC-F＝253.8Hz),138.6,134.8,129.7,128.5,127.0,126.94(d,3JC-F＝7.7Hz),126.88,125.2(d,3JC-F＝2.3Hz),125.1,119.6(d,4JC-F＝3.2Hz),117.3(d,2JC-F＝20.9Hz),78.7(d,4JC-F＝3.2Hz),38.1,27.7,27.5.19F NMR(CDCl3,565MHz):δ-125.6(dd,J1＝10.2Hz,J2＝4.0Hz).HRMS calcd for C21H20FN2O3:367.1452[M+H]+,found:367.1451.
-(tert-Butyl)-8-chloro-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3n)
White solid(41mg,54％).1H NMR(DMSO-d6,400MHz):δ8.22(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.82(td,J1＝7.6Hz,J2＝2.0Hz,1H),7.72(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.58(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.45(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.04(t,J＝8.0Hz,1H),6.45(dd,J1＝7.6Hz,J2＝1.2Hz,1H),3.18(s,3H),1.30(s,9H).13C NMR(CDCl3,150MHz):δ170.8,167.4,163.7,138.6,135.0,134.8,131.6,131.1,129.7,128.5,127.0,126.7,125.2,124.8,122.8,78.9,38.1,27.7,27.5.HRMS calcd for C21H20ClN2O3:383.1157[M+H]+,found:383.1156.
2-Isopropyl-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3o)
White solid(42mg,63％).1H NMR(CDCl3,400MHz):δ8.31(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.70(td,J1＝7.6Hz,J2＝1.6Hz,1H),7.60(td,J1＝7.6Hz,J2＝1.2Hz,,1H),7.55(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.27-7.25(m,2H),6.99-6.94(m,1H),6.38(d,J＝7.6Hz,1H),3.30(s,3H),2.84-2.77(m,1H),1.35(d,J＝6.8Hz,6H).13C NMR(CDCl3,100MHz):δ171.3,165.1,163.8,138.8,137.6,134.7,130.3,129.6,128.4,127.1,126.8,126.1,125.2,124.3,123.3,79.1,34.5,27.6,19.5,19.4.HRMS calcd for C20H19N2O3:335.1390[M+H]+,found:335.1383.
2-Cyclopropyl-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3p)
White solid(27mg,41％).1H NMR(CDCl3,400MHz):δ8.30(d,J＝7.6Hz,1H),7.70(t,J＝7.2Hz,1H),7.60(t,J＝7.6Hz,1H),7.55(d,J＝8.0Hz,1H),7.25-7.20(m,2H),6.94-6.91(m,1H),6.35(d,J＝7.6Hz,1H),3.29(s,3H),1.91-1.87(m,1H),1.26-1.15(m,2H),1.00-0.92(m,2H).13C NMR(CDCl3,150MHz):δ171.4,163.7,162.4,138.4,137.9,134.8,130.4,129.6,128.4,126.9,126.3,125.5,125.2,124.3,123.3,79.4,27.7,14.8,7.8,6.4.HRMScalcd for C20H17N2O3:333.1234[M+H]+,found:333.1233.
2-Cyclobutyl-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3q)
White solid(44mg,64％).1H NMR(DMSO-d6,400MHz):δ8.21(d,J＝8.0Hz,1H),7.83-7.79(m,1H),7.70(t,J＝7.6Hz,1H),7.58(d,J＝7.6Hz,1H),7.32-7.28(m,1H),7.20(d,J＝8.0Hz,1H),7.07-7.03(m,1H),6.44(d,J＝7.6Hz,1H),3.17(s,3H),2.48-2.41(m,3H),2.24-2.18(m,2H),2.01-1.85(m,2H).13C NMR(DMSO-d6,100MHz):δ171.4,163.5,162.6,138.9,137.4,135.5,130.7,130.4,128.3,127.7,127.6,125.9,125.1,125.0,123.9,78.9,38.3,27.8,25.3,25.0,18.2.HRMS calcd for C21H19N2O3:347.1390[M+H]+,found:347.1390.
2-Cyclopentyl-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3r)
White solid(48mg,67％).1H NMR(DMSO-d6,400MHz):δ8.21(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.81(td,J1＝7.6Hz,J2＝1.6Hz,1H),7.70(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.57(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.29(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.17(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.04(td,J1＝7.6Hz,J2＝1.6Hz,1H),6.44(dd,J1＝7.6Hz,J2＝1.2Hz,1H),3.18(s,3H),2.94-2.90(m,1H),2.02-1.88(m,4H),1.70-1.56(m,4H).13C{1H}NMR(DMSO-d6,100MHz):δ171.3,163.55,163.51,139.0,137.4,135.6,130.7,130.4,128.3,127.6,127.5,125.9,125.1,124.9,123.9,78.9,44.0,29.9,29.7,27.8,25.9.HRMS calcd forC22H21N2O3:361.1547[M+H]+,found:361.1543.
2-Cyclohexyl-2'-methyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3s)
White solid(54mg,72％).1H NMR(CDCl3,400MHz):δ8.31(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.70(td,J1＝8.0Hz,J2＝1.6Hz,1H),7.60(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.55(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.27-7.24(m,2H),6.98-6.94(m,1H),6.37(d,J＝7.6Hz,1H),3.30(s,3H),2.55-2.49(m,1H),2.16-2.08(m,2H),1.87-1.82(m,2H),1.72-1.59(m,3H),1.36-1.23(m,3H).13C NMR(CDCl3,100MHz):δ171.4,164.4,163.8,138.8,137.6,134.7,130.3,129.6,128.4,127.1,126.8,126.1,125.2,124.3,123.3,79.1,44.0,29.6,29.5,27.6,25.9,25.81,25.77.HRMS calcd for C23H23N2O3:375.1703[M+H]+,found:375.1702.
2-(tert-Butyl)-2'-ethyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3t)
White solid(55mg,76％).1H NMR(CDCl3,400MHz):δ8.31(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.69(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.59(td,J1＝8.0Hz,J2＝1.6Hz,1H),7.53(dd,J1＝7.6Hz,J2＝0.8Hz,1H),7.28-7.22(m,2H),6.98-6.94(m,1H),6.40-6.38(m,1H),4.01-3.88(m,2H),1.38(s,9H),1.09(t,J＝7.2Hz,3H).13C NMR(CDCl3,100MHz):δ170.7,166.5,163.3,138.9,137.8,134.6,130.2,129.4,128.4,126.8,126.7,126.4,125.5,124.1,123.0,79.2,37.7,36.1,27.6,12.8.HRMS calcd for C22H23N2O3:363.1703[M+H]+,found:363.1701.
2-(tert-Butyl)-2'-propyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3u)
White solid(55mg,73％).1H NMR(CDCl3,400MHz):δ8.30(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.69(td,J1＝7.6Hz,J2＝1.6Hz,1H),7.59(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.53(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.28-7.24(m,2H),6.98-6.94(m,1H),6.41-6.39(m,1H),3.89-3.83(m,2H),1.55-1.46(m,2H),1.38(s,9H),0.79(t,J＝7.6Hz,3H).13C NMR(CDCl3,100MHz):δ171.1,166.6,163.6,138.8,137.8,134.6,130.2,129.4,128.4,126.8,126.7,126.4,125.5,124.1,123.1,79.2,42.3,37.7,27.6,21.0,11.1.HRMS calcd forC23H25N2O3:377.1860[M+H]+,found:377.1853.
2-(tert-Butyl)-2'-isopropyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3v)
White solid(52mg,69％).1H NMR(CDCl3,400MHz):δ8.21(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.61(td,J1＝7.6Hz,J2＝1.6Hz,1H),7.51(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.44(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.19-7.17(m,2H),6.91-6.87(m,1H),6.38-6.36(m,1H),4.89-4.85(m,1H),1.32-1.31(m,12H),1.17(d,J＝6.8Hz,3H).13C NMR(CDCl3,100MHz):δ170.1,165.8,162.7,137.4,136.9,133.4,129.1,128.4,127.4,125.6,125.32,125.28,125.0,123.0,121.7,78.7,45.4,36.7,26.6,19.1,17.4.HRMS calcd for C23H25N2O3:377.1860[M+H]+,found:377.1853.
2-(tert-Butyl)-2'-(2-morpholinoethyl)-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3w)
White solid(54mg,60％).1H NMR(CDCl3,400MHz):δ8.29(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.69(td,J1＝7.6Hz,J2＝1.6Hz,1H),7.59(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.53(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.28-7.22(m,2H),6.96-6.92(m,1H),6.45(dd,J1＝8.0Hz,J2＝1.2Hz,1H),4.06(t,J＝6.4Hz,2H),3.45(br,4H),2.47-2.42(m,2H),2.36-2.28(m,4H),1.38(s,9H).13C NMR(CDCl3,150MHz):δ171.0,166.5,163.6,139.1,137.8,134.7,130.1,129.4,128.3,126.9,126.5,126.3,125.3,124.5,123.4,79.2,66.9,55.9,53.5,37.7,37.2,27.6.HRMS calcd for C26H30N3O4:448.2231[M+H]+,found:448.2231.
2'-Benzyl-2-(tert-butyl)-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3x)
White solid(58mg,68％).1H NMR(DMSO-d6,400MHz):δ8.23(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.85(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.72(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.57(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.30(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.18-7.16(m,4H),7.08-7.01(m,3H),6.45(dd,J1＝7.6Hz,J2＝1.2Hz,1H),5.05-4.96(m,2H),1.28(s,9H).13CNMR(CDCl3,150MHz):δ170.8,166.4,163.4,138.7,137.8,136.2,134.7.130.2,129.5,128.6,128.5,128.4,127.5,126.9,126.6,126.4,125.4,124.3,122.7,79.4,44.0,37.8,27.6.HRMS calcd for C27H25N2O3:425.1860[M+H]+,found:425.1859.
2-(tert-Butyl)-2'-(4-methoxybenzyl)-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3y)
White solid(63mg,69％).1H NMR(DMSO-d6,400MHz):δ8.22(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.84(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.71(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.56-7.54(m,1H),7.29(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.16(dd,J1＝7.6Hz,J2＝1.2Hz,1H),7.04-6.99(m,3H),6.75-6.72(m,2H),6.39(dd,J1＝7.6Hz,J2＝1.2Hz,1H),4.97-4.88(m,2H),3.67(s,3H),1.28(s,9H).13C NMR(CDCl3,100MHz):δ170.8,166.4,163.3,159.0,138.7,137.7,134.7,130.3,130.1,129.5,128.50,128.47,126.8,126.6,126.4,125.4,124.2,122.8,113.7,79.3,55.2,43.5,37.7,27.6.HRMS calcd for C28H27N2O4:455.1965[M+H]+,found:455.1964.
2-(tert-Butyl)-2'-(2,4-dimethoxybenzyl)-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3z)
White solid(77mg,79％).1H NMR(CDCl3,400MHz):δ8.26(d,J＝7.6Hz,1H),7.66(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.57-7.51(m,2H),7.27-7.20(m,2H),6.99(d,J＝7.6Hz,1H),6.88(td,J1＝7.6Hz,J2＝1.2Hz,1H),6.32(d,J＝7.6Hz,1H),6.29-6.24(m,2H),5.22(d,J＝14.4Hz,1H),4.83(d,J＝14.4Hz,1H),3.73(s,3H),3.38(s,3H),1.39(s,9H).13C NMR(CDCl3,100MHz):δ170.6,166.7,163.6,160.3,158.3,139.0,137.9,134.6,130.3,130.0,129.4,128.4,126.8,126.4,126.2,125.5,124.7,123.2,116.7,103.5,98.0,79.6,55.3,54.9,39.7,37.8,27.6.HRMS calcd for C29H29N2O5:485.2071[M+H]+,found:485.2071.
2-(tert-Butyl)-2'-phenyl-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3aa)
White solid(46mg,56％).1H NMR(CDCl3,400MHz):δ8.35(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.78-7.74(m,1H),7.66-7.62(m,2H),7.42-7.37(m,3H),7.30-7.29(m,2H),7.07-7.00(m,3H),6.64(d,J＝7.6Hz,1H),1.38(s,9H).13C NMR(CDCl3,100MHz):δ170.9,166.6,163.7,138.6,137.9,135.0,134.4,130.5,129.6,129.3,128.9,128.8,128.1,126.8,126.64,126.61,125.6,124.0,122.6,80.1,37.8,27.6.HRMS calcd for C26H23N2O3:411.1703[M+H]+,found:411.1703.
2-(tert-Butyl)-2'-(p-tolyl)-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3bb)
White solid(55mg,65％).1H NMR(CDCl3,400MHz):δ8.35-8.33(m,1H),7.77-7.72(m,1H),7.64-7.60(m,2H),7.28-7.29(m,2H),7.20(d,J＝8.0Hz,2H),7.06-7.02(m,1H),6.89(d,J＝7.6Hz,2H),6.63(d,J＝7.6Hz,1H),2.34(s,3H),1.38(s,9H).13C NMR(CDCl3,150MHz):δ171.0,166.6,163.8,138.9,138.6,137.9,135.0,131.8,130.4,130.0,129.6,128.8,127.8,126.8,126.6,125.6,124.1,122.7,80.1,37.8,27.6,21.2.HRMS calcd forC27H25N2O3:425.1860[M+H]+,found:425.1853.
2-(tert-Butyl)-2'-(4-methoxyphenyl)-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3cc)
White solid(59mg,67％).1H NMR(DMSO-d6,400MHz):δ8.23(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.87(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.74(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.62(dd,J1＝7.6Hz,J2＝0.8Hz,1H),7.35(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.21-7.14(m,2H),7.02-6.97(m,4H),6.71(dd,J1＝8.0Hz,J2＝1.2Hz,1H),3.77(s,3H),1.29(s,9H).13C NMR(CDCl3,150MHz):δ171.1,166.6,164.0,159.7,138.6,137.9,135.0,130.4,129.6,129.1,128.9,126.9,126.8,126.60,126.57,125.6,124.0,122.7,114.7,80.1,55.5,37.8,27.6.HRMS calcd for C27H25N2O4:441.1809[M+H]+,found:441.1807.
2-(tert-Butyl)-2'-(4-fluorophenyl)-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3dd)
White solid(41mg,48％).1H NMR(CDCl3,400MHz):δ8.36-8.33(m,1H),7.79-7.75(m,1H),7.67-7.63(m,2H),7.31-7.25(m,2H),7.11-7.03(m,3H),7.00-6.97(m,2H),6.62(d,J＝7.6Hz,1H),1.38(s,9H).13C NMR(CDCl3,150MHz):δ171.0,166.6,163.8,162.5(d,1JC-F＝247.2Hz),138.5,137.9,135.2,130.5,130.2(d,4JC-F＝3.2Hz),130.0(d,3JC-F＝8.7Hz),129.7,128.9,126.9,126.70,126.65,125.4,123.9,122.6,116.4(d,2JC-F＝23.0Hz),80.1,37.8,27.6.19F NMR(CDCl3,376MHz):δ-112.3--112.4(m).HRMS calcd forC26H22FN2O3:429.1609[M+H]+,found:429.1607.
2'-(4-Bromophenyl)-2-(tert-butyl)-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3ee)
White solid(44mg,45％).1H NMR(DMSO-d6,400MHz):δ8.23(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.88(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.74(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.67(d,J＝8.8Hz,2H),7.62(dd,J1＝8.0Hz,J2＝0.4Hz,1H),7.35(td,J1＝7.6Hz,J2＝1.6Hz,1H),7.20(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.17-7.09(m,3H),6.73(dd,J1＝8.0Hz,J2＝1.2Hz,1H),1.29(s,9H).13C NMR(CDCl3,100MHz):δ170.8,166.6,163.5,138.5,137.9,135.2,133.4,132.5,130.6,129.9,129.7,128.9,126.9,126.70,126.68,125.3,124.0,123.0,122.5,80.0,37.8,27.6.HRMS calcd for C26H22BrN2O3:489.0808[M+H]+,found:489.0794.
2-(tert-Butyl)-2'-(4-(trifluoromethyl)phenyl)-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3ff)
White solid(29mg,30％).1H NMR(DMSO-d6,400MHz):δ8.25(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.92-7.85(m,3H),7.76(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.64(dd,J1＝8.0Hz,J2＝0.4Hz,1H),7.41(d,J＝8.0Hz,2H),7.36(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.21(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.17(td,J1＝7.6Hz,J2＝1.2Hz,1H),6.77(dd,J1＝7.6Hz,J2＝1.2Hz,1H),1.29(s,9H).13C NMR(DMSO-d6,150MHz):δ170.7,165.8,163.4,139.1,139.0,137.3,136.0,130.9,130.5,130.2,129.7(q,2JC-F＝31.8Hz),128.7,127.8,127.4,126.7(q,3JC-F＝3.3Hz),126.4,125.4,125.1,124.4(q,1JC-F＝270.2Hz),123.2,79.6,37.8,27.7.19F NMR(DMSO-d6,376MHz):δ-61.1(s).HRMS calcd for C27H22F3N2O3:479.1577[M+H]+,found:479.1574.
2-(tert-Butyl)-2'-(3-chlorophenyl)-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3gg)
White solid(42mg,47％).1H NMR(CDCl3,400MHz):δ8.37(d,J＝7.6Hz,1H),7.80-7.76(m,1H),7.67-7.63(m,2H),7.38-7.30(m,4H),7.09-7.04(m,2H),6.92-6.89(m,1H),6.62(dd,J1＝8.0Hz,J2＝2.4Hz,1H),1.38(s,9H).13C NMR(CDCl3,100MHz):δ170.7,166.5,163.5,138.6,137.9,135.4,135.3,134.8,130.6,130.2,129.7,129.3,128.9,128.7,126.9,126.73,126.70,126.6,125.3,124.0,122.5,80.0,37.8,27.6.HRMS calcd forC26H22ClN2O3:445.1313[M+H]+,found:445.1311.
2-(tert-Butyl)-2'-(naphthalen-2-yl)-1'H-spiro[benzo[d][1,3]oxazine-4,4'-isoquinoline]-1',3'(2'H)-dione(3hh)
White solid(53mg,58％).1H NMR(DMSO-d6,400MHz):δ8.27(d,J＝7.6Hz,1H),8.00-7.97(m,2H),7.93-7.88(m,2H),7.78-7.73(m,2H),7.66(d,J＝8.0Hz,1H),7.61-7.56(m,2H),7.38(t,J＝7.6Hz,1H),7.25-7.19(m,3H),6.80(d,J＝7.6Hz,1H),1.30(s,9H).13CNMR(DMSO-d6,150MHz):δ171.0,165.8,163.7,139.1,137.4,135.9,133.3,133.0,132.7,130.9,130.5,129.3,128.8,128.3,128.2,127.9,127.7,127.43,127.38,127.2,126.6,126.4,125.5,125.0,123.3,79.7,37.8,27.8.HRMS calcd for C30H25N2O3:461.1860[M+H]+,found:461.1857.
实施例4
本发明所合成的产物螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物进行一系列反应，从而合成进一步的衍生物。例如：
向25mL圆底烧瓶中依次加入3a(34.8mg,0.1mmol)、乙醇(2mL)和NaBH4((3.0mg,0.08mmol)。将混合物于室温条件下搅拌12小时。反应结束后，加入水淬灭反应，二氯甲烷萃取三次，无水硫酸钠干燥，过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得到白色固体4a(18mg,51％)。1H NMR(DMSO-d6,400MHz)δ8.09-8.06(m,1H),7.59-7.56(m,2H),7.42-7.37(m,1H),7.24-7.20(m,3H),7.16-7.14(m,1H),6.94(d,J＝6.0Hz,1H),5.03(d,J＝6.0Hz,1H),3.07(s,3H),1.08(s,9H).13C NMR(DMSO-d6,100MHz):δ166.0,162.9,140.1,136.9,132.5,130.0,129.7,129.1,128.4,128.3,126.1,125.1,122.4,84.1,78.5,37.4,33.2,27.5.HRMS calcd for C21H22N2NaO3:373.1523[M+Na]+,found:373.1520。
向15mL反应管中依次加入3k(42.7mg,0.1mmol)、苯硼酸(18.3mg,0.15mmol)、PPh3(15.7mg,0.06mmol)、K2CO3(55.3mg,0.4mmol)、Pd(OAc)2(2.2mg,0.01mmol)和二氧六环(1mL)。进行三次抽真空充氩气后，将混合物置于80℃油浴中搅拌24h。反应结束后，冷却至室温，加入乙酸乙酯稀释，依次用水和盐水洗涤，无水硫酸钠干燥，过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20/1)得到白色固体5k(30mg,71％)。1H NMR(CDCl3,400MHz)δ8.33(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.22(td,J1＝8.0Hz,J2＝1.6Hz,1H),7.61(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.58-7.56(m,1H),7.54-7.52(m,3H),7.41-7.38(m,2H),7.34-7.31(m,1H),7.18(dd,J1＝8.0Hz,J2＝2.0Hz,1H),6.45(d,J＝8.0Hz,1H),3.32(s,3H),1.40(s,9H).13C NMR(CDCl3,100MHz):δ171.3,166.9,163.8,143.4,139.8,138.9,138.1,134.8,129.6,128.8,128.5,127.8,127.02,126.98,125.4,125.3,125.0,124.6,121.9,79.2,37.8,27.7,27.6.HRMS calcd for C27H25N2O3:425.1860[M+H]+,found:425.1857。
向15mL反应管中依次加入3g(42.7mg,0.1mmol)、苯乙烯(11.5μl,0.1mmol)、Pd(dppf)Cl2(7.3mg,0.01mmol)、Et3N(20.2mg,0.2mmol)和DMF(0.5mL)。进行三次抽真空充氩气后，将混合物置于100℃油浴中搅拌24h。反应结束后，冷却至室温，加入乙酸乙酯稀释，依次用水和盐水洗涤，无水硫酸钠干燥，过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1)得到白色固体6g(25mg,55％)。1H NMR(CDCl3,400MHz)δ8.36(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.71(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.63(td,J1＝8.0Hz,J2＝1.6Hz,1H),7.54(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.48(dd,J1＝8.4Hz,J2＝2.0Hz,1H),7.41-7.39(m,2H),7.32-7.27(m,3H),7.24-7.20(m,1H),6.85(d,J＝16.8Hz,1H),6.80(d,J＝16.4Hz,1H),6.40(d,J＝2.0Hz,1H),3.33(s,3H),1.37(s,9H).13C NMR(CDCl3,100MHz):δ171.2,166.5,163.8,138.9,137.2,136.8,136.1,134.8,129.7,128.9,128.7,128.5,127.9,127.4,127.3,127.2,126.8,126.5,125.2,123.5,122.9,79.1,37.8,27.7,27.6.HRMS calcd forC29H27N2O3:451.2016[M+H]+,found:451.2010。
向15mL反应管中依次加入3g(42.7mg,0.1mmol)、苯乙炔(16.5μl,0.1mmol)、PPh3(5.2mg,0.02mmol)、K3PO4(25.5mg,0.12mmol)、Pd(OAc)2(1.1mg,0.005mmol)和DMSO(1mL)。进行三次抽真空充氩气后，将混合物置于100℃油浴中搅拌24h。反应结束后，冷却至室温，加入乙酸乙酯稀释，依次用水和盐水洗涤，无水硫酸钠干燥，过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝50/1)得到白色固体7g(19mg,42％)。1H NMR(CDCl3,400MHz)δ8.35(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.72(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.63(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.52(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.45-7.41(m,3H),7.32-7.29(m,3H),7.25(d,J＝8.4Hz,1H),6.51(d,J＝2.0Hz,1H),3.33(s,3H),1.37(s,9H).13C NMR(CDCl3,100MHz):δ171.0,167.3,163.7,138.6,137.8,134.9,133.7,131.6,129.8,128.6,128.5,128.4,127.3,127.2,126.5,125.1,123.5,122.7,121.6,90.4,88.5,78.9,37.8,27.8,27.5.HRMS calcd for C29H25N2O3:449.1860[M+H]+,found:449.1863。
以上实施例描述了本发明的基本原理、主要特征及优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。
Claims (10)
1.一种螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物，其结构通式为：
2.如权利要求1所述螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的合成方法，其特征在于，包括如下操作：
将N-芳基脒1、重氮异喹啉二酮类化合物2、催化剂和有机溶剂混合，在氧化剂存在下，升温反应制得螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物3。
3.根据权利要求2所述螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的合成方法，其特征在于：所述有机溶剂选自甲醇、乙醇、乙腈、聚乙二醇-400或聚乙二醇-600。
4.根据权利要求2所述螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的合成方法，其特征在于：所述催化剂为二氯(五甲基环戊二烯基)合铑(III)二聚体或二氯(五甲基环戊二烯基)合铱(III)二聚体。
5.根据权利要求2所述螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的合成方法，其特征在于：反应温度为40-80℃。
6.根据权利要求2所述螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的合成方法，其特征在于：所述氧化剂为空气或氧气。
7.根据权利要求2所述螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的合成方法，其特征在于：所述N-芳基脒1、重氮异喹啉二酮类化合物2与催化剂摩尔比为1-1.5:1-1.5:0.02-0.06。
8.根据权利要求2所述螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的合成方法，其特征在于：反应中加入添加剂；添加剂选自六氟锑酸银、双三氟甲烷磺酰亚胺银盐、乙酸银、醋酸铜、醋酸铯、特戊酸、1-金刚烷甲酸、醋酸、碳酸钾或氢氧化钠。
9.根据权利要求8所述螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的合成方法，其特征在于：所述N-芳基脒1与添加剂摩尔比为1-1.5:0.2-1。
10.如权利要求1所述螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物的应用，其特征在于：将螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物3在硼氢化钠存在下还原生成化合物4；对于化合物3中R1为溴代物时，在金属钯催化剂存在下与苯硼酸、苯乙烯或苯乙炔偶联生成化合物5、化合物6或化合物7；化合物4-7结构通式为：
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210057833.6A CN114213431A (zh) | 2022-01-19 | 2022-01-19 | 螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物及其合成方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210057833.6A CN114213431A (zh) | 2022-01-19 | 2022-01-19 | 螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物及其合成方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114213431A true CN114213431A (zh) | 2022-03-22 |
Family
ID=80708480
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210057833.6A Pending CN114213431A (zh) | 2022-01-19 | 2022-01-19 | 螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物及其合成方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114213431A (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102363620A (zh) * | 2011-11-10 | 2012-02-29 | 南京工业大学 | 光致变色化合物6’-氮杂环取代-9’-酰氧基酯化螺噁嗪及其合成方法 |
| CN106866670A (zh) * | 2017-04-28 | 2017-06-20 | 遵义医学院 | 一种螺[3,5`‑吡咯[2,1‑a]异喹啉‑氧化吲哚]类化合物及其制备方法 |
| CN113185523A (zh) * | 2021-05-17 | 2021-07-30 | 河南师范大学 | 一种3-吲哚酮[螺]-3h-吲哚类化合物的合成方法 |
-
2022
- 2022-01-19 CN CN202210057833.6A patent/CN114213431A/zh active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102363620A (zh) * | 2011-11-10 | 2012-02-29 | 南京工业大学 | 光致变色化合物6’-氮杂环取代-9’-酰氧基酯化螺噁嗪及其合成方法 |
| CN106866670A (zh) * | 2017-04-28 | 2017-06-20 | 遵义医学院 | 一种螺[3,5`‑吡咯[2,1‑a]异喹啉‑氧化吲哚]类化合物及其制备方法 |
| CN113185523A (zh) * | 2021-05-17 | 2021-07-30 | 河南师范大学 | 一种3-吲哚酮[螺]-3h-吲哚类化合物的合成方法 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Frank et al. | Palladium-catalyzed vinylic substitution reactions with heterocyclic bromides | |
| EP1064243B1 (en) | Coupling reactions with palladium catalysts | |
| CN102358739B (zh) | 咪唑[1,2-a]吡啶和咪唑醛类化合物的合成方法 | |
| JP4879160B2 (ja) | ２−ブロモ又はクロロアニリンのパラジウム触媒インドール化 | |
| WO2022078306A1 (zh) | 一种大位阻氮杂环卡宾钯配合物及其制备方法与应用和基于其的索尼吉布的合成方法 | |
| CN110105359B (zh) | 一种合成茚螺异吲哚[2,1-b]异喹啉三酮类化合物的方法 | |
| Balan et al. | Efficient microwave-assisted formation of functionalized 2, 5-dihydropyrroles using ruthenium-catalyzed ring-closing metathesis | |
| CN107162968A (zh) | 一种可见光催化四氢喹啉类化合物氧化脱氢合成喹啉类化合物的方法 | |
| JPH06298731A (ja) | 複素環化合物の製造方法 | |
| CN114085217A (zh) | 一种轴手性吡啶联芳环类化合物及其制备方法 | |
| Cartoon et al. | Ortho-metallation reactions of various N-substituted pyrroles | |
| CN114213431A (zh) | 螺[苯并[d][1,3]噁嗪-异喹啉二酮]类化合物及其合成方法 | |
| CN115197228A (zh) | 吡唑啉酮[螺]二氢酞嗪和1,3-茚二酮[螺]二氢酞嗪类化合物的合成方法 | |
| CN114989178A (zh) | 一种螺[β-内酰胺-3,3’-氧化吲哚]类衍生物及其制备方法和应用 | |
| Pedrosa et al. | Synthesis of enantiopure mono-and disubstituted tetrahydroisoquinolines by 6-exo radical cyclizations | |
| CN111004164B (zh) | 一种多取代2-芳基吲哚衍生物的制备方法 | |
| CN109369496B (zh) | 一种3-芳基取代吡咯类化合物的合成方法 | |
| CN110746345B (zh) | 2-(2-氨基-5-溴-苯甲酰基)吡啶的合成方法 | |
| CN113651788A (zh) | 一种3-胺烷基色酮化合物及其制备方法 | |
| CN109608455B (zh) | 一种吲唑并[2,3-a]喹啉及其衍生物的合成方法 | |
| CN109988053B (zh) | 一种邻位烯基取代的苄醇衍生物的制备方法 | |
| CN109776338A (zh) | Salan配体、金属-Salan配合物及制备手性α-羟基-β-酮酸酯化合物的方法 | |
| JP2021502885A (ja) | ホスフィン非含有コバルト系触媒ならびにその調製のための方法および使用 | |
| CN116903534A (zh) | 一种邻苯二甲酰亚胺螺萘酮类化合物及其合成方法 | |
| Kumbhar et al. | Synthesis of quinoxalines and pyrido [2, 3-b] pyrazines by Suzuki–Miyaura cross-coupling reaction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20220322 |
|
| RJ01 | Rejection of invention patent application after publication |