CN107540597A - The preparation method of the ketone derivatives of N dimethylacetamide bases indoles 2 - Google Patents
The preparation method of the ketone derivatives of N dimethylacetamide bases indoles 2 Download PDFInfo
- Publication number
- CN107540597A CN107540597A CN201710863008.4A CN201710863008A CN107540597A CN 107540597 A CN107540597 A CN 107540597A CN 201710863008 A CN201710863008 A CN 201710863008A CN 107540597 A CN107540597 A CN 107540597A
- Authority
- CN
- China
- Prior art keywords
- reaction
- nmr
- cdcl
- preparation
- alkyl
- 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
- -1 ketone derivatives of N dimethylacetamide Chemical class 0.000 title claims abstract description 76
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 150000002475 indoles Chemical class 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 14
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 9
- 150000002940 palladium Chemical class 0.000 claims abstract description 9
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 150000002367 halogens Chemical class 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 5
- 230000000694 effects Effects 0.000 claims abstract 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 105
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 5
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 claims 9
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims 3
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical class CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 229910052763 palladium Inorganic materials 0.000 claims 2
- 238000006467 substitution reaction Methods 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 abstract description 116
- 238000000034 method Methods 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 5
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 abstract description 3
- 230000007613 environmental effect Effects 0.000 abstract description 2
- XEFCWBLINXJUIV-UHFFFAOYSA-N acetic acid;iodobenzene Chemical compound CC(O)=O.CC(O)=O.IC1=CC=CC=C1 XEFCWBLINXJUIV-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 72
- 238000005481 NMR spectroscopy Methods 0.000 description 61
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical group [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 39
- 239000012043 crude product Substances 0.000 description 36
- 239000000203 mixture Substances 0.000 description 36
- 239000003208 petroleum Substances 0.000 description 36
- 238000010898 silica gel chromatography Methods 0.000 description 36
- 238000003786 synthesis reaction Methods 0.000 description 33
- 230000015572 biosynthetic process Effects 0.000 description 32
- 150000001875 compounds Chemical class 0.000 description 18
- 150000005625 indol-2-ones Chemical class 0.000 description 9
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- QKLXBIHSGMPUQS-FGZHOGPDSA-M (3r,5r)-7-[4-(4-fluorophenyl)-2,5-dimethyl-1-phenylpyrrol-3-yl]-3,5-dihydroxyheptanoate Chemical compound CC1=C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C(C)N1C1=CC=CC=C1 QKLXBIHSGMPUQS-FGZHOGPDSA-M 0.000 description 1
- VPMIAOSOTOODMY-KJAPKAAFSA-N (4r)-6-[(e)-2-[6-tert-butyl-4-(4-fluorophenyl)-2-propan-2-ylpyridin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C([C@H](O)C1)C(=O)OC1/C=C/C=1C(C(C)C)=NC(C(C)(C)C)=CC=1C1=CC=C(F)C=C1 VPMIAOSOTOODMY-KJAPKAAFSA-N 0.000 description 1
- UTOIEVWJKDLJGE-AQRBRUGDSA-N (4r,6s)-6-[(e)-2-[4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyrimidin-5-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C=1C=C(F)C=CC=1C1=NC(C(C)C)=NC(C(C)C)=C1\C=C\[C@@H]1C[C@@H](O)CC(=O)O1 UTOIEVWJKDLJGE-AQRBRUGDSA-N 0.000 description 1
- QRDAPCMJAOQZSU-KQQUZDAGSA-N (e)-3-[4-[(e)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1-methylpyrrol-2-yl]-n-hydroxyprop-2-enamide Chemical compound C1=C(\C=C\C(=O)NO)N(C)C=C1\C=C\C(=O)C1=CC=CC(F)=C1 QRDAPCMJAOQZSU-KQQUZDAGSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- DWXSYDKEWORWBT-UHFFFAOYSA-N 2-(2-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1Br DWXSYDKEWORWBT-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- REDUQXCPUSNJOL-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O Chemical compound C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O REDUQXCPUSNJOL-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- CYSWUSAYJNCAKA-FYJFLYSWSA-N ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O Chemical compound ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O CYSWUSAYJNCAKA-FYJFLYSWSA-N 0.000 description 1
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000002365 anti-tubercular Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- KSCRVOKQPYZBHZ-IXPOFIJOSA-N benzyl n-[(2s)-1-[[(2s)-1-[[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxo-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@H]1C(NCC1)=O)C(=O)C=1SC2=CC=CC=C2N=1)C(C)C)C(=O)OCC1=CC=CC=C1 KSCRVOKQPYZBHZ-IXPOFIJOSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-N 0.000 description 1
- OZTTXCISDPJUDI-UHFFFAOYSA-N n-[2-(dimethylamino)-2-oxoethyl]-2-phenylacetamide Chemical class CN(C)C(=O)CNC(=O)CC1=CC=CC=C1 OZTTXCISDPJUDI-UHFFFAOYSA-N 0.000 description 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Landscapes
- Indole Compounds (AREA)
Abstract
本发明涉及一种N‑乙酰二甲胺基吲哚‑2‑酮衍生物的制备方法，包括以下步骤：将式(1)的取代N‑乙酰二甲胺基苯乙酰胺衍生物和二醋酸碘苯在钯盐催化剂的作用下，在有机溶剂中于25‑80℃下反应，得到式(2)的N‑乙酰二甲胺基吲哚‑2‑酮衍生物：R1、R2、R3、R4、R5、R6独立地选自氢、烷基、烷氧基、乙酰氧基、卤素或三氟甲基。本发明的方法原料易得、收率高、反应条件温和、普适性好且绿色环保。The present invention relates to a kind of preparation method of N-acetyldimethylaminoindol-2-ketone derivative, comprising the following steps: the substituted N-acetyldimethylaminophenylacetamide derivative of formula (1) and diacetic acid Iodobenzene reacts at 25-80° C. in an organic solvent under the effect of a palladium salt catalyst to obtain the N-acetyldimethylaminoindol-2-one derivative of formula (2): R 1 , R 2 , R 3 , R 4 , R 5 , R 6 are independently selected from hydrogen, alkyl, alkoxy, acetoxy, halogen or trifluoromethyl. The method of the invention has easy-to-obtain raw materials, high yield, mild reaction conditions, good universality and environmental protection.
Description
技术领域technical field
本发明涉及有机合成领域，尤其涉及一种N-乙酰二甲胺基吲哚-2-酮衍生物的制备方法。The invention relates to the field of organic synthesis, in particular to a preparation method of N-acetyldimethylaminoindol-2-one derivatives.
背景技术Background technique
吲哚-2-酮衍生物通常具有显著的生物活性和药理活性，如抗结核、抗惊厥、抗高血糖和抗弧菌，因此合成吲哚-2-酮衍生物具有重要的价值。Indol-2-one derivatives usually have significant biological and pharmacological activities, such as anti-tuberculosis, anti-convulsant, anti-hyperglycemia and anti-vibrio, so the synthesis of indol-2-one derivatives is of great value.
至今，吲哚-2-酮衍生物的合成方法主要有以下几种：So far, the synthetic methods of indol-2-one derivatives mainly contain the following types:
SU841264,1995中公开了一种吲哚-2-酮衍生物的合成方法，该方法路线较长，总收率较低。SU841264, 1995 discloses a synthesis method of indol-2-one derivatives, which has a long route and low overall yield.
利用邻溴苯乙酸为原料合成吲哚-2-酮衍生物方法，以及吲哚-2-酮的N烃基化的方法，分别在WO/2004/087658A1,2004和Organic Process Research&Development.2009,13,443-449上公开，但这些方法均具有步骤长，收率低，成本高的缺点。Using o-bromophenylacetic acid as a raw material for the synthesis of indol-2-one derivatives, and the method for the N-alkylation of indol-2-ones, respectively in WO/2004/087658A1, 2004 and Organic Process Research&Development.2009,13,443- 449, but these methods all have the disadvantages of long steps, low yield and high cost.
总之，现有技术制备吲哚-2-酮衍生物过程中存在收率较低，原料昂贵，反应条件苛刻和对环境不友好等不足。因此，从C-H键活化出发，开发反应条件温和、适用范围广泛、符合绿色化学要求的合成方法非常重要。In a word, there are disadvantages in the preparation process of indol-2-one derivatives in the prior art, such as low yield, expensive raw materials, harsh reaction conditions and unfriendly environment. Therefore, starting from the activation of C-H bonds, it is very important to develop synthetic methods with mild reaction conditions, a wide range of applications, and the requirements of green chemistry.
发明内容Contents of the invention
为解决上述技术问题，本发明的目的是提供一种N-乙酰二甲胺基吲哚-2-酮衍生物的制备方法，本发明的方法原料易得、收率高、反应条件温和、普适性好且绿色环保。In order to solve the above-mentioned technical problems, the purpose of this invention is to provide a kind of preparation method of N-acetyldimethylamino indol-2-one derivative, the method raw material of the present invention is easy to get, yield is high, reaction condition is gentle, general Good adaptability and green environmental protection.
本发明提供了一种N-乙酰二甲胺基吲哚-2-酮衍生物的制备方法，其特征在于，包括以下步骤：The invention provides a kind of preparation method of N-acetyldimethylaminoindol-2-one derivative, it is characterized in that, comprises the following steps:
将式(1)的取代N-乙酰二甲胺基苯乙酰胺衍生物和二醋酸碘苯(PhI(OAc)2)在钯盐催化剂的作用下，在有机溶剂中于25-80℃下反应，得到式(2)的N-乙酰二甲胺基吲哚-2-酮衍生物：Reaction of substituted N-acetyldimethylaminophenylacetamide derivatives of formula (1) and iodobenzene diacetate (PhI(OAc) 2 ) in an organic solvent under the action of a palladium salt catalyst at 25-80°C , to obtain N-acetyldimethylaminoindol-2-one derivatives of formula (2):
其中，R1、R2、R3、R4、R5、R6独立地选自氢、烷基、烷氧基、乙酰氧基、卤素、芳香基或三氟甲基。其中，R5所连接的碳原子上的另外一个取代基团为氢或甲基。Wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 are independently selected from hydrogen, alkyl, alkoxy, acetoxy, halogen, aryl or trifluoromethyl. Wherein, another substituting group on the carbon atom to which R 5 is connected is hydrogen or methyl.
进一步地，R1、R2、R3、R4、R5、R6均为氢；Further, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are all hydrogen;
或R1、R2、R3、R4的其中一者为烷基、烷氧基、芳香基、卤素或三氟甲基，其他三者均为氢，R5、R6均为氢；Or one of R 1 , R 2 , R 3 , and R 4 is alkyl, alkoxy, aryl, halogen or trifluoromethyl, the other three are hydrogen, and R 5 and R 6 are both hydrogen;
或R1、R2、R4、R5均为氢，R3为烷基或芳香基，R6为C1-C6烷基；Or R 1 , R 2 , R 4 , and R 5 are all hydrogen, R 3 is an alkyl or aryl group, and R 6 is a C 1 -C 6 alkyl group;
或R4、R6均为氢，R5为烷基或乙酰氧基，R1、R2或R3中的其中一者为烷基、芳香基或卤素，其他二者均为氢。Or R 4 and R 6 are both hydrogen, R 5 is alkyl or acetoxy, one of R 1 , R 2 or R 3 is alkyl, aryl or halogen, and the other two are hydrogen.
进一步地，烷基为C1-C6烷基。优选地，烷基为甲基、乙基、丁基、异丙基、丁基、环丁基或环己基。Further, the alkyl group is a C 1 -C 6 alkyl group. Preferably, the alkyl group is methyl, ethyl, butyl, isopropyl, butyl, cyclobutyl or cyclohexyl.
进一步地，烷氧基为C1-C6烷氧基。优选地，烷氧基为甲氧基。Further, alkoxy is C 1 -C 6 alkoxy. Preferably, alkoxy is methoxy.
进一步地，芳香基为苯基。Further, the aromatic group is phenyl.
进一步地，卤素为氯、溴或碘。Further, halogen is chlorine, bromine or iodine.
进一步地，钯盐催化剂为醋酸钯(Pd(OAc)2)或氯化钯。优选地，钯盐催化剂为醋酸钯。Further, the palladium salt catalyst is palladium acetate (Pd(OAc) 2 ) or palladium chloride. Preferably, the palladium salt catalyst is palladium acetate.
进一步地，有机溶剂为甲苯、1,2-二氯乙烷(DCE)、四氢呋喃(THF)、1,4-二氧六环或醋酸酐。优选地，有机溶剂为甲苯。Further, the organic solvent is toluene, 1,2-dichloroethane (DCE), tetrahydrofuran (THF), 1,4-dioxane or acetic anhydride. Preferably, the organic solvent is toluene.
进一步地，取代N-乙酰二甲胺基苯乙酰胺衍生物、二醋酸碘苯和钯盐催化剂的摩尔比为1:1-2:0.05-0.1。优选地，取代N-乙酰二甲胺基苯乙酰胺衍生物、二醋酸碘苯和钯盐催化剂的摩尔比为1:1.5:0.05。Further, the molar ratio of the substituted N-acetyldimethylaminophenylacetamide derivative, iodobenzene diacetate and palladium salt catalyst is 1:1-2:0.05-0.1. Preferably, the molar ratio of the substituted N-acetyldimethylaminophenylacetamide derivative, iodobenzene diacetate and palladium salt catalyst is 1:1.5:0.05.
优选地，反应温度为60℃。Preferably, the reaction temperature is 60°C.
借由上述方案，本发明至少具有以下优点：By means of the above solution, the present invention has at least the following advantages:
1.本发明使用取代N-乙酰二甲胺-苯乙酰胺衍生物衍生物为起始物，原料易得、种类多样；利用本发明的方法得到的产物类型多样，既可以直接使用、又可以用于其他进一步的反应。1. The present invention uses substituted N-acetyldimethylamine-phenylacetamide derivative derivatives as the starting material, and the raw materials are easy to get and various in type; the products obtained by the method of the present invention are various in type, which can be used directly or for other further reactions.
2.本发明反应条件温和、反应操作和后处理过程简单，产率很高，适合于规模生产。2. The present invention has mild reaction conditions, simple reaction operation and post-treatment process, high yield and is suitable for large-scale production.
上述说明仅是本发明技术方案的概述，为了能够更清楚了解本发明的技术手段，并可依照说明书的内容予以实施，以下以本发明的较佳实施例并配合详细说明如后。The above description is only an overview of the technical solutions of the present invention. In order to understand the technical means of the present invention more clearly and implement them according to the contents of the description, the preferred embodiments of the present invention are described in detail below.
具体实施方式detailed description
下面结合实施例，对本发明的具体实施方式作进一步详细描述。以下实施例用于说明本发明，但不用来限制本发明的范围。以下方程式中的Me代表甲基(CH3)。Below in conjunction with the examples, the specific implementation of the present invention will be further described in detail. The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention. Me in the following equations represents a methyl group (CH 3 ).
实施例1N-乙酰二甲胺基吲哚-2-酮的合成The synthesis of embodiment 1N-acetyldimethylaminoindol-2-ketone
(1)称取N-乙酰二甲胺基苯乙酰胺1a(0.0440g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2a。分离产率为86％。(1) Weigh N-acetyldimethylaminophenylacetamide 1a (0.0440g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2a. The isolated yield was 86%.
(2)称取N-乙酰二甲胺基苯乙酰胺1a(0.0440g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到80℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2a。分离产率为83％。(2) Weigh N-acetyldimethylaminophenylacetamide 1a (0.0440g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g, 0.3 mmol). The mixture was heated to 80°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2a. The isolated yield was 83%.
(3)称取N-乙酰二甲胺基苯乙酰胺1a(0.0440g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物在25℃反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2a。分离产率为53％。(3) Weigh N-acetyldimethylaminophenylacetamide 1a (0.0440g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g, 0.3 mmol). The mixture was reacted at 25°C, followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2a. Isolated yield was 53%.
(4)(2)称取N-乙酰二甲胺基苯乙酰胺1a(0.0440g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL 1,2-二氯乙烷(DCE)中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到80℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2a。分离产率为67％。(4)(2) Weigh N-acetyldimethylaminophenylacetamide 1a (0.0440g, 0.2mmol), and dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL 1,2-dichloroethane (DCE) , PhI(OAc) 2 (0.0966 g, 0.3 mmol) was added. The mixture was heated to 80°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2a. Isolated yield was 67%.
(5)称取N-乙酰二甲胺基苯乙酰胺1a(0.0440g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL四氢呋喃(THF)中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到80℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2a。分离产率为22％。(5) Weigh N-acetyldimethylaminophenylacetamide 1a (0.0440g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL tetrahydrofuran (THF), add PhI(OAc) 2 (0.0966 g, 0.3 mmol). The mixture was heated to 80°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2a. Isolated yield was 22%.
(6)称取N-乙酰二甲胺基苯乙酰胺1a(0.0440g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL1，4-二氧六环中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到80℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2a。分离产率为45％。(6) Weigh N-acetyldimethylaminophenylacetamide 1a (0.0440g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL of 1,4-dioxane, add PhI(OAc) 2 (0.0966 g, 0.3 mmol). The mixture was heated to 80°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2a. Isolated yield was 45%.
(7)称取N-乙酰二甲胺基苯乙酰胺1a(0.0440g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL醋酸酐中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到80℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2a。分离产率为17％。对上述产物进行核磁和质谱分析，结果如下：(7) Weigh N-acetyldimethylaminophenylacetamide 1a (0.0440g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL acetic anhydride, add PhI(OAc) 2 (0.0966g, 0.3 mmol). The mixture was heated to 80°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2a. Isolated yield was 17%. Above-mentioned product is carried out NMR and mass spectrum analysis, and the results are as follows:
2a:1H NMR(400MHz,CDCl3)δ7.26–7.21(m,2H),7.04-7.00(m,1H),6.80(d,J＝7.60Hz,1H),4.51(s,2H),3.59(s,2H),3.11(s,3H),2.96(s,3H)；13C NMR(101MHz,CDCl3)δδ175.30,166.16,144.52,128.00,124.46,124.28,122.64,108.99,41.88,36.72,35.92,35.71；HRMS(ESI-TOF)m/z calcd for C12H14N2O2[M+H]+:219.1134,Found:219.1123.2a: 1 H NMR (400MHz, CDCl 3 ) δ7.26–7.21(m,2H),7.04-7.00(m,1H),6.80(d,J=7.60Hz,1H),4.51(s,2H), 3.59(s,2H),3.11(s,3H),2.96(s,3H); 13 C NMR(101MHz,CDCl 3 )δδ175.30,166.16,144.52,128.00,124.46,124.28,122.64,108.99,41.88,36.72, 35.92,35.71; HRMS(ESI-TOF)m/z calcd for C 12 H 14 N 2 O 2 [M+H] + :219.1134,Found:219.1123.
实施例二：6-甲氧基-N-乙酰二甲胺基吲哚-2-酮的合成Example 2: Synthesis of 6-methoxy-N-acetyldimethylaminoindol-2-one
称取4-甲氧基-N-乙酰二甲胺基苯乙酰胺1b(0.0500g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯(toluene)中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2b。分离产率为91％。对产物进行核磁和质谱分析，结果如下：Weigh 4-methoxy-N-acetyldimethylaminophenylacetamide 1b (0.0500g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2b. The isolated yield was 91%. The product was analyzed by NMR and mass spectrometry, the results are as follows:
2b:1H NMR(400MHz,CDCl3)δ7.12(d,J＝8.40Hz,1H),6.53(d,J＝8.00Hz,1H),6.42(s,1H),4.49(s,2H),3.79(s,3H),3.53(s,2H),3.11(s,3H),2.97(s,3H)；13C NMR(101MHz,CDCl3)δ176.18,166.18,160.23,145.83,125.06,116.26,106.80,97.21,55.77,42.09,36.86,36.07,35.26；HRMS Calcd for C13H16N2O3[M+H]+:249.1239,Found:249.1242.2b: 1 H NMR (400MHz, CDCl 3 ) δ7.12(d, J＝8.40Hz, 1H), 6.53(d, J＝8.00Hz, 1H), 6.42(s, 1H), 4.49(s, 2H) ,3.79(s,3H),3.53(s,2H),3.11(s,3H),2.97(s,3H); 13 C NMR(101MHz,CDCl 3 )δ176.18,166.18,160.23,145.83,125.06,116.26, 106.80,97.21,55.77,42.09,36.86,36.07,35.26; HRMS Calcd for C 13 H 16 N 2 O 3 [M+H] + :249.1239,Found:249.1242.
实施例三：6-甲基-N-乙酰二甲胺基吲哚-2-酮的合成Example 3: Synthesis of 6-methyl-N-acetyldimethylaminoindol-2-one
称取4-甲基-N-乙酰二甲胺基苯乙酰胺1c(0.0468g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2c。分离产率为88％。Weigh 4-methyl-N-acetyldimethylaminophenylacetamide 1c (0.0468g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g , 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2c. The isolated yield was 88%.
2c:1H NMR(400MHz,CDCl3)δ7.11(d,J＝7.60Hz,1H),6.83(d,J＝7.60Hz,1H),6.63(s,1H),4.50(s,2H),3.55(s,2H),3.12(s,3H),2.98(s,3H),2.34(s,3H).；13C NMR(101MHz,CDCl3)δ175.81,166.37,144.73,138.18,124.30,123.35,121.37,109.94,42.03,36.86,36.07,35.60,22.02；HRMS Calcd for C13H16N2O2[M+H]+:233.1290,Found:233.1297.2c: 1 H NMR (400MHz, CDCl 3 ) δ7.11(d, J=7.60Hz, 1H), 6.83(d, J=7.60Hz, 1H), 6.63(s, 1H), 4.50(s, 2H) ,3.55(s,2H),3.12(s,3H),2.98(s,3H),2.34(s,3H).; 13 C NMR(101MHz,CDCl 3 )δ175.81,166.37,144.73,138.18,124.30,123.35 ,121.37,109.94,42.03,36.86,36.07,35.60,22.02; HRMS Calcd for C 13 H 16 N 2 O 2 [M+H] + :233.1290,Found:233.1297.
实施例四：6-三氟甲基-N-乙酰二甲胺基吲哚-2-酮的合成Example 4: Synthesis of 6-trifluoromethyl-N-acetyldimethylaminoindol-2-one
称取4-三氟甲基-N-乙酰二甲胺基苯乙酰胺1d(0.0576g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2d。分离产率为54％。Weigh 4-trifluoromethyl-N-acetyldimethylaminophenylacetamide 1d (0.0576g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 ( 0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2d. Isolated yield was 54%.
2d:1H NMR(400MHz,CDCl3)δ7.35–7.29(dd,J＝17.60,9.60Hz,2H),6.96(s,1H),4.53(s,2H),3.64(s,2H),3.14(s,3H),2.98(s,3H)；13C NMR(101MHz,CDCl3)δ175.00,165.54,145.32,130.63(q,JC-F＝32.33Hz),128.38,124.78,124.24(q,JC-F＝243.00Hz),119.78(q,JC-F＝4.00Hz),105.70(q,JC-F＝3.67Hz),41.77,36.71,36.05,35.64；19F NMR(376MHz,CDCl3)δ-62.22；HRMS Calcd for C13H13F3N2O2[M+H]+:287.1007,Found:287.0998.2d: 1 H NMR (400MHz, CDCl 3 ) δ7.35–7.29 (dd, J=17.60, 9.60Hz, 2H), 6.96(s, 1H), 4.53(s, 2H), 3.64(s, 2H), 3.14(s,3H),2.98(s,3H); 13 C NMR(101MHz,CDCl 3 )δ175.00,165.54,145.32,130.63(q,J CF ＝32.33Hz),128.38,124.78,124.24(q,J CF =243.00Hz), 119.78(q, J CF =4.00Hz), 105.70 (q, J CF =3.67Hz), 41.77, 36.71, 36.05, 35.64; 19 F NMR (376MHz, CDCl 3 ) δ-62.22; HRMS Calcd for C 13 H 13 F 3 N 2 O 2 [M+H] + :287.1007,Found:287.0998.
实施例五：6-溴-N-乙酰二甲胺基吲哚-2-酮的合成Example five: Synthesis of 6-bromo-N-acetyldimethylaminoindol-2-one
称取4-溴-N-乙酰二甲胺基苯乙酰胺1e(0.0596g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2e。分离产率为63％。Weigh 4-bromo-N-acetyldimethylaminophenylacetamide 1e (0.0596g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2e. Isolated yield was 63%.
2e:1H NMR(400MHz,CDCl3)δ7.3(s,1H),7.36(d,J＝8.40Hz,1H),6.69(d,J＝8.00Hz,1H),4.50(s,2H),3.60(s,2H),3.11(s,3H),2.97(s,3H)；13C NMR(101MHz,CDCl3)δ174.69,165.93,143.79,131.00,127.78,126.41,115.40,110.60,41.99,36.84,36.06,35.65；HRMS Calcd for C13H13BrN2O2[M+H]+:297.0239,Found:297.0225.2e: 1 H NMR (400MHz, CDCl 3 ) δ7.3(s, 1H), 7.36(d, J=8.40Hz, 1H), 6.69(d, J=8.00Hz, 1H), 4.50(s, 2H) ,3.60(s,2H),3.11(s,3H),2.97(s,3H); 13 C NMR(101MHz,CDCl 3 )δ174.69,165.93,143.79,131.00,127.78,126.41,115.40,110.60,41.99,36.84 ,36.06,35.65; HRMS Calcd for C 13 H 13 BrN 2 O 2 [M+H] + :297.0239,Found:297.0225.
实施例六：6-苯基-N-乙酰二甲胺基吲哚-2-酮的合成Example 6: Synthesis of 6-phenyl-N-acetyldimethylaminoindol-2-one
称取4-苯基-N-乙酰二甲胺基苯乙酰胺1f(0.0582g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2f。分离产率为78％。Weigh 4-phenyl-N-acetyldimethylaminophenylacetamide 1f (0.0582g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g , 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2f. Isolated yield was 78%.
2f:1H NMR(400MHz,CDCl3)δ7.56(d,J＝6.80Hz,2H),7.44–7.41(m,2H),7.35(d,J＝7.60Hz,1H),7.30(d,J＝7.60Hz,1H),7.25(d,J＝8.00Hz,1H),6.99(s,1H),4.56(s,2H),3.63(s,2H),3.13(s,3H),2.97(s,3H)；13C NMR(101MHz,CDCl3)δ175.63,166.13,145.22,141.74,141.37,128.93,127.63,127.50,124.77,123.46,121.82,108.02,42.01,36.82,36.05,35.63；HRMS Calcd for C18H18N2O2[M+H]+:295.1447,Found:295.1436.2f: 1 H NMR (400MHz, CDCl 3 ) δ7.56(d, J=6.80Hz, 2H), 7.44–7.41(m, 2H), 7.35(d, J=7.60Hz, 1H), 7.30(d, J＝7.60Hz, 1H), 7.25(d, J＝8.00Hz, 1H), 6.99(s, 1H), 4.56(s, 2H), 3.63(s, 2H), 3.13(s, 3H), 2.97( s, 3H); 13 C NMR (101MHz, CDCl 3 ) δ175.63, 166.13, 145.22, 141.74, 141.37, 128.93, 127.63, 127.50, 124.77, 123.46, 121.82, 108.02, 42.01, 36.82, 356.05 for CMS; Cal for CMS 18 H 18 N 2 O 2 [M+H] + :295.1447, Found: 295.1436.
实施例七：6-氯-N-乙酰二甲胺基吲哚-2-酮的合成Example 7: Synthesis of 6-chloro-N-acetyldimethylaminoindol-2-one
称取4-氯-N-乙酰二甲胺基苯乙酰胺1g(0.0508g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2g。分离产率为73％。Weigh 1 g of 4-chloro-N-acetyldimethylaminophenylacetamide (0.0508 g, 0.2 mmol), dissolve palladium acetate (0.0022 g, 0.01 mmol) in 1 mL of toluene, add PhI(OAc) 2 (0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2g. Isolated yield was 73%.
2g:1H NMR(400MHz,CDCl3)δ7.14(d,J＝7.9Hz,1H),6.98(d,J＝9.7Hz,1H),6.76(s,1H),4.47(s,2H),3.55(s,2H),3.11(s,3H),2.97(s,3H)；13C NMR(101MHz,CDCl3)δ175.37(s),165.70(s),145.85(s),133.85(s),125.42(s),122.72(s),122.60(s),109.74(s),41.82(s),36.73(s),36.05(s),35.36(s)；HRMS Calcd for C12H13ClN2O2[M+H]+:253.0666,Found:253.0660.2g: 1 H NMR (400MHz, CDCl 3 ) δ7.14(d, J=7.9Hz, 1H), 6.98(d, J=9.7Hz, 1H), 6.76(s, 1H), 4.47(s, 2H) ,3.55(s,2H),3.11(s,3H),2.97(s,3H); 13 C NMR(101MHz,CDCl 3 )δ175.37(s),165.70(s),145.85(s),133.85( s), 125.42(s), 122.72(s), 122.60(s), 109.74(s), 41.82(s), 36.73(s), 36.05(s), 35.36(s); HRMS Calcd for C 12 H 13 ClN 2 O 2 [M+H] + :253.0666,Found:253.0660.
实施例八：5-碘-N-乙酰二甲胺基吲哚-2-酮的合成Example 8: Synthesis of 5-iodo-N-acetyldimethylaminoindol-2-one
称取3-碘-N-乙酰二甲胺基苯乙酰胺1h(0.0672g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2h。分离产率为56％。Weigh 3-iodo-N-acetyldimethylaminophenylacetamide for 1h (0.0672g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2h. Isolated yield was 56%.
2h:1H NMR(400MHz,CDCl3)δ7.54(s,2H),6.59(d,J＝8.00Hz,1H),4.49(s,2H),3.58(s,2H),3.11(s,3H),2.96(s,3H)；13C NMR(101MHz,CDCl3)δ170.28,167.90,138.38,137.20,136.55,130.68,128.76,94.91,43.04,41.65,36.08,35.77；HRMS Calcd forC12H13IN2O2[M+H+]:345.0022,Found:345.0010.2h: 1 H NMR (400MHz, CDCl 3 ) δ7.54(s, 2H), 6.59(d, J=8.00Hz, 1H), 4.49(s, 2H), 3.58(s, 2H), 3.11(s, 3H), 2.96(s, 3H); 13 C NMR (101MHz, CDCl 3 ) δ170.28, 167.90, 138.38, 137.20, 136.55, 130.68, 128.76, 94.91, 43.04, 41.65, 36.08, 35.77; HRMS Calcd for 13 IN 12 H 2 O 2 [M+H + ]: 345.0022, Found: 345.0010.
实施例九：5-三氟甲基-N-乙酰二甲胺基吲哚-2-酮的合成Example 9: Synthesis of 5-trifluoromethyl-N-acetyldimethylaminoindol-2-one
称取3-三氟甲基-N-乙酰二甲胺基苯乙酰胺1i(0.0576g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2i。分离产率为58％。Weigh 3-trifluoromethyl-N-acetyldimethylaminophenylacetamide 1i (0.0576g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 ( 0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2i. Isolated yield was 58%.
2i:1H NMR(400MHz,CDCl3)δ7.52(d,J＝9.00Hz,1H),7.50(s,1H),6.86(d,J＝8.00Hz,1H),4.55(s,2H),3.65(s,2H),3.14(s,3H),2.98(s,3H)；13C NMR(101MHz,CDCl3)δ175.12,165.73,147.68,135.63(q,JC-F＝34.33Hz),125.94(q,JC-F＝4.33Hz),123.24(q,JC-F＝286.12Hz),124.89,121.73(q,JC-F＝4.00Hz),108.93,41.90,36.82,36.08,35.56；HRMS Calcd for C13H13F3N2O2[M+H]+:287.1007,Found:287.0999.2i: 1 H NMR (400MHz, CDCl 3 ) δ7.52(d, J=9.00Hz, 1H), 7.50(s, 1H), 6.86(d, J=8.00Hz, 1H), 4.55(s, 2H) , 3.65(s, 2H), 3.14(s, 3H), 2.98(s, 3H); 13 C NMR (101MHz, CDCl 3 ) δ175.12, 165.73, 147.68, 135.63(q, J CF =34.33Hz), 125.94( q,J CF ＝4.33Hz),123.24(q,J CF ＝286.12Hz),124.89,121.73(q,J CF ＝4.00Hz),108.93,41.90,36.82,36.08,35.56; HRMS Calcd for C 13 H 13 F 3 N 2 O 2 [M+H] + :287.1007, Found: 287.0999.
实施例十：5-溴-N-乙酰二甲胺基吲哚-2-酮的合成Example 10: Synthesis of 5-bromo-N-acetyldimethylaminoindol-2-one
称取3-溴-N-乙酰二甲胺基苯乙酰胺1j(0.0596g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2j。分离产率为62％。Weigh 3-bromo-N-acetyldimethylaminophenylacetamide 1j (0.0596g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2j. Isolated yield was 62%.
2j:1H NMR(400MHz,CDCl3)δ7.37(s,1H),7.36(d,J＝7.60Hz,1H),6.69(d,J＝8.40Hz,1H),4.50(s,2H),3.60(s,2H),3.12(s,3H),2.97(s,3H)；13C NMR(101MHz,CDCl3)δ174.69,165.93,143.79,131.00,127.78,126.41,115.40,110.60,41.99,36.84,36.06,35.65；HRMS Calcd for C12H13BrN2O2[M+H]+:297.0239,Found:297.0229.2j: 1 H NMR (400MHz, CDCl 3 ) δ7.37(s, 1H), 7.36(d, J=7.60Hz, 1H), 6.69(d, J=8.40Hz, 1H), 4.50(s, 2H) ,3.60(s,2H),3.12(s,3H),2.97(s,3H); 13 C NMR(101MHz,CDCl 3 )δ174.69,165.93,143.79,131.00,127.78,126.41,115.40,110.60,41.99,36.84 ,36.06,35.65; HRMS Calcd for C 12 H 13 BrN 2 O 2 [M+H] + :297.0239,Found:297.0229.
实施例十一：5-氯-N-乙酰二甲胺基吲哚-2-酮的合成Embodiment 11: Synthesis of 5-chloro-N-acetyldimethylaminoindol-2-one
称取3-氯-N-乙酰二甲胺基苯乙酰胺1k(0.0508g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2k。分离产率为70％。Weigh 3-chloro-N-acetyldimethylaminophenylacetamide 1k (0.0508g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate=1:2) to obtain compound 2k. Isolated yield was 70%.
2k:1H NMR(400MHz,CDCl3)δ7.23(s,1H),7.21(d,J＝11.60Hz,1H),6.72(d,J＝8.00Hz,1H),4.50(s,2H),3.59(s,2H),3.11(s,3H),2.97(s,3H)；13C NMR(101MHz,CDCl3)δ174.82,165.97,143.28,128.07,126.01,125.02,110.07,41.99,36.83,36.04,35.73；HRMSCalcd for C12H13ClN2O2[M+H]+:253.0666,Found:253.0650.2k: 1 H NMR (400MHz, CDCl 3 ) δ7.23(s,1H),7.21(d,J=11.60Hz,1H),6.72(d,J=8.00Hz,1H),4.50(s,2H) ,3.59(s,2H),3.11(s,3H),2.97(s,3H); 13 C NMR(101MHz,CDCl 3 )δ174.82,165.97,143.28,128.07,126.01,125.02,110.07,41.99,36.83,36.04 ,35.73; HRMS Calcd for C 12 H 13 ClN 2 O 2 [M+H] + :253.0666,Found:253.0650.
实施例十二：4-甲氧基-N-乙酰二甲胺基吲哚-2-酮的合成Example 12: Synthesis of 4-methoxy-N-acetyldimethylaminoindol-2-one
称取2-甲氧基-N-乙酰二甲胺基苯乙酰胺1l(0.0500g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2l。分离产率为85％。Weigh 2-methoxy-N-acetyldimethylaminophenylacetamide 1l (0.0500g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 21. The isolated yield was 85%.
2l:1H NMR(400MHz,CDCl3)δ7.23-7.19(m,1H),6.60(d,J＝8.40Hz,1H),6.49(d,J＝4.00Hz,1H),4.50(s,2H),3.85(s,3H),3.52(s,2H),3.10(s,3H),2.97(s,3H)；13C NMR(101MHz,CDCl3)δ175.72,166.41,145.81,129.43,111.12,105.81,102.55,55.68,42.30,36.86,36.06,33.56；HRMS Calcd for C13H16N2O3[M+H]+:249.1239,Found:249.1236.2l: 1 H NMR (400MHz, CDCl 3 ) δ7.23-7.19 (m, 1H), 6.60 (d, J = 8.40Hz, 1H), 6.49 (d, J = 4.00Hz, 1H), 4.50 (s, 2H),3.85(s,3H),3.52(s,2H),3.10(s,3H),2.97(s,3H); 13 C NMR(101MHz,CDCl 3 )δ175.72,166.41,145.81,129.43,111.12, 105.81,102.55,55.68,42.30,36.86,36.06,33.56; HRMS Calcd for C 13 H 16 N 2 O 3 [M+H] + :249.1239,Found:249.1236.
实施例十三：4-溴-N-乙酰二甲胺基吲哚-2-酮的合成Example 13: Synthesis of 4-bromo-N-acetyldimethylaminoindol-2-one
称取2-溴-N-乙酰二甲胺基苯乙酰胺1m(0.0596g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2m。分离产率为57％。Weigh 1m of 2-bromo-N-acetyldimethylaminophenylacetamide (0.0596g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL of toluene, add PhI(OAc) 2 (0.0966g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2m. Isolated yield was 57%.
2m:1H NMR(400MHz,CDCl3)δ7.18(d,J＝7.20Hz,1H),7.15-7.11(m,1H),6.76(d,J＝7.60Hz,1H),4.52(s,2H),3.57(s,2H),3.13(s,3H),2.99(s,3H)；13C NMR(101MHz,CDCl3)δ174.04,165.87,145.54,129.63,125.61,125.31,119.18,107.93,42.07,37.11,36.76,35.99；HRMS Calcd for C12H13BrN2O2[M+H]+:297.0239,Found:297.0223.2m: 1 H NMR (400MHz, CDCl 3 ) δ7.18(d, J=7.20Hz, 1H), 7.15-7.11(m, 1H), 6.76(d, J=7.60Hz, 1H), 4.52(s, 2H),3.57(s,2H),3.13(s,3H),2.99(s,3H); 13 C NMR(101MHz,CDCl 3 )δ174.04,165.87,145.54,129.63,125.61,125.31,119.18,107.93,42.07 ,37.11,36.76,35.99; HRMS Calcd for C 12 H 13 BrN 2 O 2 [M+H] + :297.0239,Found:297.0223.
实施例十四：4-碘-N-乙酰二甲胺基吲哚-2-酮的合成Example 14: Synthesis of 4-iodo-N-acetyldimethylaminoindol-2-one
称取2-碘-N-乙酰二甲胺基苯乙酰胺1n(0.0692g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2n。分离产率为55％。Weigh 2-iodo-N-acetyldimethylaminophenylacetamide 1n (0.0692g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2n. Isolated yield was 55%.
2n:1H NMR(400MHz,CDCl3)δ7.38(d,J＝8.00Hz,1H),6.99-6.95(m,1H),6.77(d,J＝7.60Hz,1H),4.48(s,2H),3.48(s,2H),3.12(s,3H),2.97(s,3H).；13C NMR(101MHz,CDCl3)δ173.61,165.93,144.81,131.59,129.81,108.75,92.40,42.19,40.54,36.86,36.07；HRMS Calcd for C12H13IN2O2[M+H]+:345.0022,Found:345.0008.2n: 1 H NMR (400MHz, CDCl 3 ) δ7.38(d, J=8.00Hz, 1H), 6.99-6.95(m, 1H), 6.77(d, J=7.60Hz, 1H), 4.48(s, 2H), 3.48(s, 2H), 3.12(s, 3H), 2.97(s, 3H).; 13 C NMR (101MHz, CDCl 3 ) δ173.61, 165.93, 144.81, 131.59, 129.81, 108.75, 92.40, 42.19, 40.54, 36.86, 36.07; HRMS Calcd for C 12 H 13 IN 2 O 2 [M+H] + :345.0022, Found: 345.0008.
实施例十五：4-甲基-N-乙酰二甲胺基吲哚-2-酮的合成Example 15: Synthesis of 4-methyl-N-acetyldimethylaminoindol-2-one
称取2-甲基-N-乙酰二甲胺基苯乙酰胺1o(0.0468g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2o。分离产率为82％。Weigh 2-methyl-N-acetyldimethylaminophenylacetamide 1o (0.0468g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g , 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2o. The isolated yield was 82%.
2o:1H NMR(400MHz,CDCl3)δ7.16-7.12(m,1H),6.85(d,J＝8.00Hz,1H),6.64(d,J＝7.60Hz,1H),4.50(s,2H),3.48(s,2H),3.10(s,3H),2.96(s,3H),2.26(s,3H)；13C NMR(101MHz,CDCl3)δ175.39,166.31,144.31,134.18,128.07,123.99,123.10,106.57,42.13,36.80,36.00,34.79,18.72；HRMS Calcd for C13H16N2O2[M+H]+:233.1290,Found:233.1277.2o: 1 H NMR (400MHz, CDCl 3 ) δ7.16-7.12 (m, 1H), 6.85 (d, J = 8.00Hz, 1H), 6.64 (d, J = 7.60Hz, 1H), 4.50 (s, 2H),3.48(s,2H),3.10(s,3H),2.96(s,3H),2.26(s,3H); 13 C NMR(101MHz,CDCl 3 )δ175.39,166.31,144.31,134.18,128.07, 123.99,123.10,106.57,42.13,36.80,36.00,34.79,18.72; HRMS Calcd for C 13 H 16 N 2 O 2 [M+H] + :233.1290,Found:233.1277.
实施例十六：4，6-二甲基-N-乙酰二甲胺基吲哚-2-酮的合成Example 16: Synthesis of 4,6-dimethyl-N-acetyldimethylaminoindol-2-one
称取2,4-二甲基-N-乙酰二甲胺基苯乙酰胺1p(0.0496g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2p。分离产率为62％。Weigh 2,4-dimethyl-N-acetyldimethylaminophenylacetamide 1p (0.0496g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g, 0.3mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2p. Isolated yield was 62%.
2p:1H NMR(400MHz,CDCl3)δ6.67(s,1H),6.47(s,1H),4.48(s,2H),3.43(s,2H),3.11(s,3H),2.97(s,3H),2.30(s,3H),2.21(s,3H)；13C NMR(101MHz,CDCl3)δ175.78,166.38,144.37,138.06,133.82,124.65,120.10,107.38,42.10,36.78,36.01,34.56,21.88,18.64；HRMS Calcd for C14H18N2O2[M+H]+:247.1447,Found:247.1443.2p: 1 H NMR (400MHz, CDCl 3 ) δ6.67(s,1H),6.47(s,1H),4.48(s,2H),3.43(s,2H),3.11(s,3H),2.97( s,3H),2.30(s,3H),2.21(s,3H); 13 C NMR(101MHz,CDCl 3 )δ175.78,166.38,144.37,138.06,133.82,124.65,120.10,107.38,42.10,36.78,36.01, 34.56, 21.88, 18.64; HRMS Calcd for C 14 H 18 N 2 O 2 [M+H] + :247.1447, Found: 247.1443.
实施例十七：4，6-二氯-N-乙酰二甲胺基吲哚-2-酮的合成Example 17: Synthesis of 4,6-dichloro-N-acetyldimethylaminoindol-2-one
称取2,4-二氯-N-乙酰二甲胺基苯乙酰胺1q(0.0576g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2q。分离产率为47％。Weigh 2,4-dichloro-N-acetyldimethylaminophenylacetamide 1q (0.0576g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 ( 0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2q. Isolated yield was 47%.
2q:1H NMR(400MHz,CDCl3)δ7.03(s,1H),6.68(s,1H),4.47(s,2H),3.56(s,2H),3.12(s,3H),2.98(s,3H)；13C NMR(101MHz,CDCl3)δ174.28,165.44,146.46,134.73,130.98,122.57,121.49,108.38,42.02,36.75,36.09,34.99；HRMS Calcd forC12H12Cl2N2O2[M+H+]:287.0354,Found:287.0229.2q: 1 H NMR (400MHz, CDCl 3 ) δ7.03(s,1H),6.68(s,1H),4.47(s,2H),3.56(s,2H),3.12(s,3H),2.98( s, 3H); 13 C NMR (101MHz, CDCl 3 ) δ174.28, 165.44, 146.46, 134.73, 130.98, 122.57, 121.49, 108.38, 42.02, 36.75, 36.09, 34.99; HRMS Calcd for C 12 H 12 O 2 Cl 2 N [M+H + ]:287.0354,Found:287.0229.
实施例十八：5，6-二甲氧基-N-乙酰二甲胺基吲哚-2-酮的合成Example 18: Synthesis of 5,6-dimethoxy-N-acetyldimethylaminoindol-2-one
称取3,4-二甲氧基-N-乙酰二甲胺基苯乙酰胺1s(0.0560g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2s。分离产率为51％。Weigh 3,4-dimethoxy-N-acetyldimethylaminophenylacetamide 1s (0.0560g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2s. Isolated yield was 51%.
2s:1H NMR(400MHz,CDCl3)δ6.87(s,1H),6.57(s,1H),4.50(s,2H),3.89(s,3H),3.84(s,3H),3.54(s,2H),3.12(s,3H),2.97(s,3H)；13C NMR(101MHz,CDCl3)δ175.70,166.68,149.65,145.41,138.45,115.10,109.92,95.70,57.15,56.68,42.57,37.11,36.10,35.93；HRMS Calcd for C14H18Cl2N2O4[M+H+]:279.1345,Found:279.1300.2s: 1 H NMR (400MHz, CDCl 3 ) δ6.87(s,1H),6.57(s,1H),4.50(s,2H),3.89(s,3H),3.84(s,3H),3.54( s,2H),3.12(s,3H),2.97(s,3H); 13 C NMR(101MHz,CDCl 3 )δ175.70,166.68,149.65,145.41,138.45,115.10,109.92,95.70,57.15,56.68,42.57, 37.11, 36.10, 35.93; HRMS Calcd for C 14 H 18 Cl 2 N 2 O 4 [M+H + ]: 279.1345, Found: 279.1300.
实施例十九：5，6-二氯-N-乙酰二甲胺基吲哚-2-酮的合成Example 19: Synthesis of 5,6-dichloro-N-acetyldimethylaminoindol-2-one
称取3,4-二氯-N-乙酰二甲胺基苯乙酰胺1t(0.0576g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2t。分离产率为52％。Weigh 3,4-dichloro-N-acetyldimethylaminophenylacetamide 1t (0.0576g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 ( 0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2t. Isolated yield was 52%.
2t:1H NMR(400MHz,CDCl3)δ7.31(s,1H),6.86(s,1H),4.48(s,2H),3.57(s,2H),3.12(s,3H),2.98(s,3H)；13C NMR(101MHz,CDCl3)δ174.71,165.49,144.33,132.04,126.37,124.31,111.05,41.90,36.76,36.09,35.29；HRMS Calcd for C12H12Cl2N2O2[M+H+]:287.0354,Found:287.0330.2t: 1 H NMR (400MHz, CDCl 3 ) δ7.31(s,1H),6.86(s,1H),4.48(s,2H),3.57(s,2H),3.12(s,3H),2.98( s, 3H); 13 C NMR (101MHz, CDCl 3 ) δ174.71, 165.49, 144.33, 132.04, 126.37, 124.31, 111.05, 41.90, 36.76, 36.09, 35.29; HRMS Calcd for C 12 H 12 Cl 2 N 2 O 2 [ M+H + ]:287.0354,Found:287.0330.
实施例二十：3-甲基-6-异丁基-N-乙酰二甲胺基吲哚-2-酮的合成Example 20: Synthesis of 3-methyl-6-isobutyl-N-acetyldimethylaminoindol-2-one
称取4-异丁基-α-甲基-N-乙酰二甲胺基苯乙酰胺1u(0.0580g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2u。分离产率为91％。Weigh 4-isobutyl-α-methyl-N-acetyldimethylaminophenylacetamide 1u (0.0580g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI ( OAc) 2 (0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2u. The isolated yield was 91%.
2u:1H NMR(400MHz,CDCl3)δ7.12(d,J＝7.60Hz,1H),6.82(d,J＝7.60Hz,1H),6.62(s,1H),4.55–4.43(m,2H),3.10(s,3H),2.96(s,3H),2.45(d,J＝7.20Hz,2H),1.88–1.81(m,1H),1.48(d,J＝7.60Hz,3H),0.89(d,J＝6.80Hz,6H)；13C NMR(101MHz,CDCl3)δ179.26,166.45,143.29,142.05,127.87,123.50,123.22,109.72,45.85,42.18,40.41,36.87,36.01,30.44,22.59,22.57,15.80；HRMS Calcd for C17H24N2O2[M+H+]:289.1916.；Found:289.1905.2u: 1 H NMR (400MHz, CDCl 3 ) δ7.12(d, J=7.60Hz, 1H), 6.82(d, J=7.60Hz, 1H), 6.62(s, 1H), 4.55–4.43(m, 2H), 3.10(s, 3H), 2.96(s, 3H), 2.45(d, J=7.20Hz, 2H), 1.88–1.81(m, 1H), 1.48(d, J=7.60Hz, 3H), 0.89 (d, J=6.80Hz, 6H); 13 C NMR (101MHz, CDCl 3 ) δ179.26, 166.45, 143.29, 142.05, 127.87, 123.50, 123.22, 109.72, 45.85, 42.18, 40.41, 35.87, 30.491, 2 , 22.57, 15.80; HRMS Calcd for C 17 H 24 N 2 O 2 [M+H + ]: 289.1916.; Found: 289.1905.
实施例二十一：3,3-二甲基-N-乙酰二甲胺基吲哚-2-酮的合成Example 21: Synthesis of 3,3-dimethyl-N-acetyldimethylaminoindol-2-one
称取α，α-二甲基-N-乙酰二甲胺基苯乙酰胺1v(0.0496g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2v。分离产率为92％。Weigh α,α-dimethyl-N-acetyldimethylaminophenylacetamide 1v (0.0496g, 0.2mmol), and dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966g, 0.3mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2v. The isolated yield was 92%.
2v:1H NMR(400MHz,CDCl3)δ7.22–7.19(m,2H),7.06-7.03(m,1H),6.83(d,J＝7.60Hz,1H),4.51(s,2H),3.09(s,3H),2.96(s,3H),1.41(s,6H)；13C NMR(101MHz,CDCl3)δ181.62,166.37,142.05,135.64,127.86,122.81,122.43,108.95,44.34,41.98,36.75,35.98,24.65；HRMS Calcd for C14H18N2O2[M+H+]:247.1447,Found:247.1434.2v: 1 H NMR (400MHz, CDCl 3 )δ7.22–7.19(m,2H),7.06-7.03(m,1H),6.83(d,J＝7.60Hz,1H),4.51(s,2H), 3.09(s,3H),2.96(s,3H),1.41(s,6H); 13 C NMR(101MHz,CDCl 3 )δ181.62,166.37,142.05,135.64,127.86,122.81,122.43,108.95,44.34,41.98, 36.75, 35.98, 24.65; HRMS Calcd for C 14 H 18 N 2 O 2 [M+H + ]: 247.1447, Found: 247.1434.
实施例二十二：3-乙酰氧基-4-氯-N-乙酰二甲胺基吲哚-2-酮的合成Example 22: Synthesis of 3-acetoxy-4-chloro-N-acetyldimethylaminoindol-2-one
称取2-氯-α-乙酰氧基-N-乙酰二甲胺基苯乙酰胺1w(0.0624g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2w。分离产率为84％。Weigh 2-chloro-α-acetoxy-N-acetyldimethylaminophenylacetamide 1w (0.0624g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc ) 2 (0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2w. The isolated yield was 84%.
2w:1H NMR(400MHz,CDCl3)δ7.27-7.23(m,1H),7.02(d,J＝8.40Hz,1H),6.76(d,J＝8.00Hz,1H),6.18(s,1H),4.66(d,J＝16.40Hz,1H),4.34(d,J＝16.40Hz,1H),3.11(s,3H),2.98(s,3H),2.20(s,3H)；13C NMR(101MHz,CDCl3)δ171.77,169.67,165.66,145.57,131.68,131.66,121.64,108.22,69.00,42.48,36.91,36.09,20.52；HRMS Calcd forC14H15ClN2O2[M+H+]:311.0799,Found:311.0790.2w: 1 H NMR (400MHz, CDCl 3 ) δ7.27-7.23(m, 1H), 7.02(d, J＝8.40Hz, 1H), 6.76(d, J＝8.00Hz, 1H), 6.18(s, 1H), 4.66(d, J=16.40Hz, 1H), 4.34(d, J=16.40Hz, 1H), 3.11(s, 3H), 2.98(s, 3H), 2.20(s, 3H); 13 C NMR (101MHz, CDCl 3 ) δ171.77, 169.67, 165.66, 145.57, 131.68, 131.66, 121.64, 108.22, 69.00, 42.48, 36.91, 36.09, 20.52; HRMS Calcd for C 14 H 15 H + ClN 2 O 2 ] [M: 311.0799,Found:311.0790.
实施例二十三：α-乙酰氧基-N-乙酰二甲胺基吲哚-2-酮的合成Example 23: Synthesis of α-Acetoxy-N-acetyldimethylaminoindol-2-one
称取α-乙酰氧基-N-乙酰二甲胺基苯乙酰胺1x(0.0556g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2x。分离产率为91％。Weigh α-acetoxy-N-acetyldimethylaminophenylacetamide 1x (0.0556g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc) 2 (0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2x. The isolated yield was 91%.
2x:1H NMR(400MHz,CDCl3)δ7.35(d,J＝7.20Hz,1H),7.32-7.28(m,1H),7.07-7.03(m,1H),6.84(d,J＝7.60Hz,1H),6.05(s,1H),4.63(d,J＝8.00Hz,1H),4.39(d,J＝8.00Hz,1H),3.11(s,3H),2.98(s,3H),2.19(s,3H)；13C NMR(101MHz,CDCl3)δ172.55,170.52,165.85,144.01,130.56,125.83,124.37,123.47,109.64,70.04,42.27,36.90,36.08,20.95；HRMS Calcd for C14H16N2O4[M+H+]:277.1188,Found:277.1182.2x: 1 H NMR (400MHz, CDCl 3 ) δ7.35(d, J=7.20Hz, 1H), 7.32-7.28(m, 1H), 7.07-7.03(m, 1H), 6.84(d, J=7.60 Hz,1H),6.05(s,1H),4.63(d,J=8.00Hz,1H),4.39(d,J=8.00Hz,1H),3.11(s,3H),2.98(s,3H), for CMS _ 16 N 2 O 4 [M+H + ]: 277.1188, Found: 277.1182.
实施例二十四：2-(6’-氯-2’氧代螺[环丁-1，3’吲哚啉]-1-基)-N,N二甲基乙酰胺的合成Example 24: Synthesis of 2-(6'-chloro-2'oxospiro[cyclobutane-1,3'indoline]-1-yl)-N,N dimethylacetamide
称取1-(4-氯苯基)-N-乙酰二甲胺基环丁基甲酰胺1y(0.0520g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2y。分离产率为92％。Weigh 1-(4-chlorophenyl)-N-acetyldimethylaminocyclobutylformamide 1y (0.0520g, 0.2mmol), dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL toluene, add PhI(OAc ) 2 (0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2y. The isolated yield was 92%.
2y:1H NMR(400MHz,CDCl3)δ7.38(d,J＝8.00Hz,1H),7.02(d,J＝7.60Hz,1H),6.73(s,1H),4.43(s,2H),3.08(s,3H),2.94(s,3H),2.68–2.58(m,2H),2.38–2.27(m,3H),2.26–2.13(m,1H)；13C NMR(101MHz,CDCl3)δ180.42,165.88,143.58,133.53,132.46,109.30,47.86,41.80,36.67,35.94,31.57,16.81；HRMS Calcd for C14H15ClN2O2[M+H+]:293.1057,Found:293.1047.2y: 1 H NMR (400MHz, CDCl 3 ) δ7.38(d, J＝8.00Hz, 1H), 7.02(d, J＝7.60Hz, 1H), 6.73(s, 1H), 4.43(s, 2H) , 3.08(s,3H), 2.94(s,3H), 2.68–2.58(m,2H), 2.38–2.27(m,3H), 2.26–2.13(m,1H); 13 C NMR (101MHz, CDCl 3 )δ180.42,165.88,143.58,133.53,132.46,109.30,47.86,41.80,36.67,35.94,31.57,16.81; HRMS Calcd for C 14 H 15 ClN 2 O 2 [M+H + ]:293.1057,Found:2793
实施例二十五：N,N-二甲基-2-(6-甲基-2-氧代吲哚啉-1-基)丙酰胺的合成Example 25: Synthesis of N,N-dimethyl-2-(6-methyl-2-oxoindolin-1-yl)propionamide
称取N,N-二甲基-2-(2-(对甲苯基)乙酰胺基)丙酰胺1z(0.0496g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2z。分离产率为72％。Weigh N,N-dimethyl-2-(2-(p-tolyl)acetamido)propionamide 1z (0.0496g, 0.2mmol), and dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL of toluene, PhI(OAc) 2 (0.0966 g, 0.3 mmol) was added. The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2z. Isolated yield was 72%.
2z:1H NMR(400MHz,CDCl3)δ7.12(d,J＝7.60Hz,1H),7.01(s,1H),6.85(d,J＝7.20Hz,1H),5.42(q,J＝6.80Hz,1H),3.51(s,2H),2.94(s,3H),2.90(s,3H),2.34(s,3H),1.51(d,J＝6.80Hz,3H)；13C NMR(101MHz,CDCl3)δ174.62,169.39,142.79,138.55,124.29,123.35,121.46,111.85,47.10,37.21,36.52,35.20,22.10,14.85；HRMS Calcd forC14H18N2O2[M+H+]:247.1447,Found:247.1444.2z: 1 H NMR (400MHz, CDCl 3 ) δ7.12(d, J=7.60Hz, 1H), 7.01(s, 1H), 6.85(d, J=7.20Hz, 1H), 5.42(q, J= 6.80Hz, 1H), 3.51(s, 2H), 2.94(s, 3H), 2.90(s, 3H), 2.34(s, 3H), 1.51(d, J=6.80Hz, 3H); 13C NMR( 101MHz, CDCl 3 )δ174.62, 169.39, 142.79, 138.55, 124.29, 123.35, 121.46, 111.85, 47.10, 37.21, 36.52, 35.20, 22.10, 14.85; HRMS Calcd forC 14 H + 18 : N 2 O 2 [ 247.1447,Found: 247.1444.
实施例二十六：N,N-二甲基-2-(6-甲基-2-氧代吲哚啉-1-基)丁酰胺的合成Example 26: Synthesis of N,N-dimethyl-2-(6-methyl-2-oxoindolin-1-yl)butanamide
称取N,N-二甲基-2-(2-(对甲苯基)乙酰胺基)丁酰胺1Ⅰ(0.0524g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2Ⅰ。分离产率为70％。Weigh N,N-dimethyl-2-(2-(p-tolyl)acetamido)butanamide 1I (0.0524g, 0.2mmol), and dissolve palladium acetate (0.0022g, 0.01mmol) in 1mL of toluene, PhI(OAc) 2 (0.0966 g, 0.3 mmol) was added. The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2I. Isolated yield was 70%.
2Ⅰ:1H NMR(400MHz,CDCl3)δ7.11(d,J＝7.60Hz,1H),7.08(s,1H),6.84(d,J＝7.60Hz,1H),5.23–5.19(m,1H),3.60–3.46(m,2H),2.95(s,3H),2.93(s,3H),2.33(s,3H),2.16–1.98(m,2H),0.87(t,J＝7.40Hz,3H)；13C NMR(101MHz,CDCl3)δ175.26,169.00,142.97,138.47,124.17,123.33,121.31,112.30,52.93,37.24,36.40,35.09,22.10,22.03,10.61；HRMS Calcd for C15H20N2O2[M+H+]:261.1603,Found:261.1599.2Ⅰ: 1 H NMR (400MHz, CDCl 3 ) δ7.11(d, J=7.60Hz, 1H), 7.08(s, 1H), 6.84(d, J=7.60Hz, 1H), 5.23–5.19(m, 1H),3.60–3.46(m,2H),2.95(s,3H),2.93(s,3H),2.33(s,3H),2.16–1.98(m,2H),0.87(t,J＝7.40Hz ,3H); 13 C NMR (101MHz, CDCl 3 ) δ175.26, 169.00, 142.97, 138.47, 124.17, 123.33 , 121.31, 112.30, 52.93, 37.24, 36.40, 35.09, 22.10, 22.03, 10.61 for Hdc for CMS 10 HR N 2 O 2 [M+H + ]: 261.1603, Found: 261.1599.
实施例二十七：N,N,3-三甲基-2-(6-甲基-2-氧代吲哚啉-1-基)丁酰胺的合成Example 27: Synthesis of N,N,3-trimethyl-2-(6-methyl-2-oxoindolin-1-yl)butanamide
称取N,N,3-三甲基-2-(2-(对甲苯基)乙酰胺基)丁酰胺1Ⅱ(0.0552g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2Ⅱ。分离产率为70％。Weigh N,N,3-trimethyl-2-(2-(p-tolyl)acetamido)butanamide 1II (0.0552g, 0.2mmol), palladium acetate (0.0022g, 0.01mmol) was dissolved in 1mL toluene , PhI(OAc) 2 (0.0966 g, 0.3 mmol) was added. The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2II. Isolated yield was 70%.
2Ⅱ:1H NMR(400MHz,CDCl3)δ7.33(s,1H),7.10(d,J＝7.60Hz,1H),6.84(d,J＝7.60Hz,1H),4.94(d,J＝10.80Hz,1H),3.04(s,3H),2.94(s,3H),2.91–2.82(m,1H),2.34(s,3H),1.05(d,J＝6.40Hz,3H),0.75(d,J＝6.80Hz,3H)；13C NMR(101MHz,CDCl3)δ175.59,168.38,143.36,138.42,124.01,123.34,121.10,113.17,57.36,37.50,36.31,35.09,26.84,22.16,20.55,18.44；HRMS Calcd for C16H22N2O2[M+H+]:275.1760,Found:275.1444.2Ⅱ: 1 H NMR (400MHz, CDCl 3 ) δ7.33(s, 1H), 7.10(d, J=7.60Hz, 1H), 6.84(d, J=7.60Hz, 1H), 4.94(d, J= 10.80Hz,1H),3.04(s,3H),2.94(s,3H),2.91–2.82(m,1H),2.34(s,3H),1.05(d,J＝6.40Hz,3H),0.75( d, J＝6.80Hz, 3H); 13 C NMR (101MHz, CDCl 3 ) δ175.59, 168.38, 143.36, 138.42, 124.01, 123.34, 121.10, 113.17, 57.36, 37.50, 36.31, 35.09, 26.84, 22.456, 12 ; HRMS Calcd for C 16 H 22 N 2 O 2 [M+H + ]: 275.1760, Found: 275.1444.
实施例二十八：N,N,4-三甲基-2-(6-甲基-2-氧代吲哚啉-1-基)戊酰胺的合成Example 28: Synthesis of N,N,4-trimethyl-2-(6-methyl-2-oxoindolin-1-yl)pentanamide
称取N,N,4-三甲基-2-(2-(对甲苯基)乙酰胺基)戊酰胺1Ⅲ(0.0580g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2Ⅲ。分离产率为55％。Weigh N,N,4-trimethyl-2-(2-(p-tolyl)acetamido)pentanamide 1Ⅲ (0.0580g, 0.2mmol), palladium acetate (0.0022g, 0.01mmol) was dissolved in 1mL toluene , PhI(OAc) 2 (0.0966 g, 0.3 mmol) was added. The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2III. Isolated yield was 55%.
2Ⅲ:1H NMR(400MHz,CDCl3)δ7.11(d,J＝4.80Hz,1H),7.10(s,1H),6.84(d,J＝7.60Hz,1H),5.39(t,J＝7.40Hz,1H),3.51(q,J＝16.90Hz,2H),2.97(s,3H),2.93(s,3H),1.95(t,J＝7.00Hz,2H),1.49–1.41(m,1H),0.98(d,J＝6.80Hz,3H),0.89(d,J＝6.80Hz,3H)；13C NMR(101MHz,CDCl3)δ175.02,169.25,143.10,138.45,124.15,123.28,121.41,112.45,49.68,37.67,37.34,36.50,35.15,24.87,23.35,22.43,22.14；HRMS Calcd forC17H24N2O2[M+H+]:289.1916,Found:289.1911.2Ⅲ: 1 H NMR (400MHz, CDCl 3 ) δ7.11(d, J=4.80Hz, 1H), 7.10(s, 1H), 6.84(d, J=7.60Hz, 1H), 5.39(t, J= 7.40Hz, 1H), 3.51(q, J=16.90Hz, 2H), 2.97(s, 3H), 2.93(s, 3H), 1.95(t, J=7.00Hz, 2H), 1.49–1.41(m, 1H), 0.98(d, J=6.80Hz, 3H), 0.89(d, J=6.80Hz, 3H); 13 C NMR (101MHz, CDCl 3 ) δ175.02, 169.25, 143.10, 138.45, 124.15, 123.28, 121.41, 112.45, 49.68, 37.67, 37.34, 36.50, 35.15, 24.87, 23.35, 22.43, 22.14; HRMS Calcd for C 17 H 24 N 2 O 2 [M+H + ]: 289.1916, Found: 289.1911.
实施例二十九：N,N,3-三甲基-2-(6-甲基-2-氧代吲哚啉-1-基)戊酰胺的合成Example 29: Synthesis of N,N,3-trimethyl-2-(6-methyl-2-oxoindolin-1-yl)pentanamide
称取N,N,3-三甲基-2-(2-(对甲苯基)乙酰胺基)戊酰胺1Ⅳ(0.0580g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2Ⅳ。分离产率为54％。Weigh N,N,3-trimethyl-2-(2-(p-tolyl)acetamido)pentanamide 1Ⅳ (0.0580g, 0.2mmol), palladium acetate (0.0022g, 0.01mmol) was dissolved in 1mL toluene , PhI(OAc) 2 (0.0966 g, 0.3 mmol) was added. The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2IV. Isolated yield was 54%.
2Ⅳ:1H NMR(400MHz,CDCl3)δ7.35(s,1H),7.08(d,J＝7.60Hz,1H),6.83(d,J＝7.60Hz,1H),5.03(d,J＝10.80Hz,1H),3.59–3.43(m,2H),3.06(s,3H),2.93(s,3H),2.70–2.61(m,1H),2.34(s,3H),1.21–1.14(m,1H),1.03-0.92(m,1H),0.98(d,J＝6.40Hz,3H),0.79(t,J＝7.40Hz,3H)；13C NMR(101MHz,CDCl3)δ175.56,168.48,143.43,138.35,123.93,123.28,121.08,113.31,56.18,37.56,36.30,35.09,32.56,24.35,22.13,16.51,10.92；HRMS Calcd for C17H24N2O2[M+H+]:289.1916,Found:289.1905.2Ⅳ: 1 H NMR (400MHz, CDCl 3 ) δ7.35(s, 1H), 7.08(d, J=7.60Hz, 1H), 6.83(d, J=7.60Hz, 1H), 5.03(d, J= 10.80Hz,1H),3.59–3.43(m,2H),3.06(s,3H),2.93(s,3H),2.70–2.61(m,1H),2.34(s,3H),1.21–1.14(m ,1H),1.03-0.92(m,1H),0.98(d,J=6.40Hz,3H),0.79(t,J=7.40Hz,3H); 13 C NMR(101MHz,CDCl 3 )δ175.56,168.48, 143.43,138.35,123.93,123.28,121.08,113.31,56.18,37.56,36.30,35.09,32.56,24.35,22.13,16.51,10.92; HRMS Calcd for C 17 H 24 N 2 O 2 [M+H.1 + ]9:1 Found: 289.1905.
实施例三十：2-环己基-N,N,-二甲基-2-(6-甲基-2-氧代吲哚啉-1-基)乙酰胺的合成Example 30: Synthesis of 2-cyclohexyl-N,N,-dimethyl-2-(6-methyl-2-oxoindolin-1-yl)acetamide
称取2-环己基-N,N,-二甲基-2-(2-(对甲苯基)乙酰胺基)乙酰胺1Ⅴ(0.0632g,0.2mmol)，醋酸钯(0.0022g,0.01mmol)溶于1mL甲苯中，加入PhI(OAc)2(0.0966g，0.3mmol)。混合物加热到60℃，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚:乙酸乙酯＝1:2)提纯后得到化合物2Ⅴ。分离产率为48％。Weigh 2-cyclohexyl-N,N,-dimethyl-2-(2-(p-tolyl)acetamido)acetamide 1V (0.0632g, 0.2mmol), palladium acetate (0.0022g, 0.01mmol) Dissolve in 1 mL of toluene and add PhI(OAc) 2 (0.0966 g, 0.3 mmol). The mixture was heated to 60°C, and the reaction was followed by TLC until the reaction was completely completed. After the reaction, the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:2) to obtain compound 2V. Isolated yield was 48%.
2Ⅴ:1H NMR(400MHz,CDCl3)δ7.32(s,1H),7.07(d,J＝7.60Hz,1H),6.81(d,J＝7.60Hz,1H),5.01(d,J＝10.80Hz,1H),3.57–3.41(m,2H),3.01(s,3H),2.90(s,3H),2.57-2.49(m,1H),2.33(s,3H),1.91(d,J＝12.00Hz,1H),1.69(d,J＝12.00Hz,1H),1.61(s,2H),1.34–1.24(m,2H),1.11(t,J＝9.40Hz,2H),0.98–0.86(m,2H)；13C NMR(101MHz,CDCl3)δ175.49,168.20,143.39,138.29,123.87,123.21,120.97,113.03,56.01,37.39,36.17,35.48,34.95,31.09,28.13,26.40,25.77,25.72,22.07；HRMS Calcd for C19H26N2O2[M+H+]:315.2073,Found:315.2066.2Ⅴ: 1 H NMR (400MHz, CDCl 3 ) δ7.32(s, 1H), 7.07(d, J=7.60Hz, 1H), 6.81(d, J=7.60Hz, 1H), 5.01(d, J= 10.80Hz,1H),3.57–3.41(m,2H),3.01(s,3H),2.90(s,3H),2.57-2.49(m,1H),2.33(s,3H),1.91(d,J =12.00Hz,1H),1.69(d,J=12.00Hz,1H),1.61(s,2H),1.34–1.24(m,2H),1.11(t,J=9.40Hz,2H),0.98–0.86 (m,2H); 13 C NMR(101MHz,CDCl 3 )δ175.49,168.20,143.39,138.29,123.87,123.21,120.97,113.03,56.01,37.39,36.17,35.48,34.95,31.09,27.402,25.25 ,22.07; HRMS Calcd for C 19 H 26 N 2 O 2 [M+H + ]: 315.2073, Found: 315.2066.
总之，本发明公开了一种吲哚-2-酮衍生物的制备方法，以取代2-苯乙酰胺基乙酰二甲胺衍生物为底物，以醋酸钯等钯盐为催化剂，在甲苯等有机溶剂中，与二醋酸碘苯在25-80℃反应，可高收率的制得多个吲哚-2-酮衍生物衍生物。In a word, the present invention discloses a preparation method of indol-2-one derivatives, which uses substituted 2-phenylacetamidoacetyldimethylamine derivatives as substrates, palladium acetate and other palladium salts as catalysts, in toluene, etc. In an organic solvent, it reacts with iodobenzene diacetate at 25-80°C to prepare multiple indol-2-one derivatives in high yield.
以上所述仅是本发明的优选实施方式，并不用于限制本发明，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明技术原理的前提下，还可以做出若干改进和变型，这些改进和变型也应视为本发明的保护范围。The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention. It should be pointed out that for those of ordinary skill in the art, some improvements can be made without departing from the technical principle of the present invention. and modifications, these improvements and modifications should also be considered as the protection scope of the present invention.
Claims (8)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710863008.4A CN107540597A (en) | 2017-09-22 | 2017-09-22 | The preparation method of the ketone derivatives of N dimethylacetamide bases indoles 2 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710863008.4A CN107540597A (en) | 2017-09-22 | 2017-09-22 | The preparation method of the ketone derivatives of N dimethylacetamide bases indoles 2 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107540597A true CN107540597A (en) | 2018-01-05 |
Family
ID=60964232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710863008.4A Pending CN107540597A (en) | 2017-09-22 | 2017-09-22 | The preparation method of the ketone derivatives of N dimethylacetamide bases indoles 2 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107540597A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113214134A (en) * | 2021-04-30 | 2021-08-06 | 南通大学 | Synthesis method of quaternary carbon oxoindole skeleton |
| US11365210B2 (en) | 2014-02-24 | 2022-06-21 | Ventana Medical Systems, Inc. | Quinone methide analog signal amplification |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004087658A1 (en) * | 2003-03-31 | 2004-10-14 | Ucb, S.A. | Indolone-acetamide derivatives, processes for preparing them and their uses |
-
2017
- 2017-09-22 CN CN201710863008.4A patent/CN107540597A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004087658A1 (en) * | 2003-03-31 | 2004-10-14 | Ucb, S.A. | Indolone-acetamide derivatives, processes for preparing them and their uses |
Non-Patent Citations (3)
| Title |
|---|
| FABIENNE BROEDERS ET AL.: "Practical Syntheses of Oxindole Derivatives: Chemical Development towards 2-(5-Chloro-2-oxo-2,3-dihydroindol-1-yl)acetamide and (S)-2-(5-Chloro-2-oxo-2,3-dihydroindol-1-yl)propionamide", 《ORGANIC PROCESS RESEARCH & DEVELOPMENT》 * |
| GANG HE ET AL.: "Use of a Readily Removable Auxiliary Group for the Synthesis of Pyrrolidones by the Palladium-Catalyzed Intramolecular Amination of Unactivated γ C(sp3)-H Bonds", 《ANGEW. CHEM. INT. ED.》 * |
| MINGYU GUAN ET AL.: "Pd-Catalyzed sequential β-C(sp3)-H arylation and intramolecular amination of δ-C(sp2)-H bonds for synthesis of quinolinones via an N,O-bidentate directing group", 《CHEM. COMMUN.》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11365210B2 (en) | 2014-02-24 | 2022-06-21 | Ventana Medical Systems, Inc. | Quinone methide analog signal amplification |
| US11780863B2 (en) * | 2014-02-24 | 2023-10-10 | Ventana Medical Systems, Inc. | Quinone methide analog signal amplification |
| US12215118B2 (en) | 2014-02-24 | 2025-02-04 | Ventana Medical Systems, Inc. | Quinone methide analog signal amplification |
| CN113214134A (en) * | 2021-04-30 | 2021-08-06 | 南通大学 | Synthesis method of quaternary carbon oxoindole skeleton |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107540597A (en) | The preparation method of the ketone derivatives of N dimethylacetamide bases indoles 2 | |
| CN109678788B (en) | A kind of 1,2-diaryl indole, derivative and synthetic method thereof | |
| CN110483364A (en) | A kind of indolone sulfone compound and its synthetic method | |
| She et al. | One-pot synthesis of functionalized benzimidazoles and 1H-pyrimidines via cascade reactions of o-aminoanilines or naphthalene-1, 8-diamine with alkynes and p-tolylsulfonyl azide | |
| CN104710429B (en) | Method for chiral spirocyclic phosphoric acid catalyzed synthesis of optically active quinoxaline derivative | |
| CN110396094B (en) | Quinolinone heteroaromatic ring compound and derivative and synthetic method thereof | |
| CN106892863A (en) | The preparation method of vismodegib and its intermediate | |
| CN109020877B (en) | A kind of alkyl-modified arylpyridine compound and preparation method thereof | |
| CN115246786B (en) | Preparation method of indole compound or benzoxazine compound | |
| Inahashi et al. | Efficient N-tert-butoxycarbonylation of indoles with di-tert-butyl dicarbonate catalyzed by cesium fluoride | |
| CN106278989B (en) | The synthetic method of 3- cyanogen radical indole compounds | |
| CN113173877B (en) | Indole acetyl imino sulfone series compounds and preparation method thereof | |
| Zhang et al. | Friedel-crafts alkylation of indoles by tert-enamides in acetic acid | |
| CN110372722B (en) | Method for synthesizing sulfur-nitrogen-containing bis-heterocyclic compound | |
| CN114292153A (en) | High-efficiency synthesis method of aryl halide | |
| CN103694157B (en) | A kind of method of preparing chirality alpha-chloro aziridine | |
| CN113651788A (en) | A kind of 3-aminoalkyl chromone compound and preparation method thereof | |
| CN112174962A (en) | Synthesis method of benzo [ e ] pyridylimidazo [4,5-g ] isoindole-1, 3(2H) -diketone compound | |
| CN113754544A (en) | A kind of preparation method of polysubstituted (E)-trifluoromethyl olefin | |
| CN104262167B (en) | A kind of preparation method of diaryl-amine derivative | |
| CN108675951A (en) | A kind of synthetic method of 2- alkenyls indole -3-carboxylic acid ester type compound | |
| Shibata et al. | Efficient synthesis of bicyclic α-hydroxy-α-trifluoromethyl-γ-lactams | |
| CN109574904A (en) | A kind of trifluoromethyl substituted-dihydro Benzazole compounds and preparation method thereof | |
| CN111808072B (en) | A kind of synthetic method of 3-formyl indole derivative | |
| CN115403505B (en) | A method for preparing a thioester compound containing an indole ketone structure |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180105 |