CN109912603A - A kind of practical approach using N- methoxyamide as nitrogen source synthesizing new bioactive molecule - Google Patents
A kind of practical approach using N- methoxyamide as nitrogen source synthesizing new bioactive molecule Download PDFInfo
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- CN109912603A CN109912603A CN201910248529.8A CN201910248529A CN109912603A CN 109912603 A CN109912603 A CN 109912603A CN 201910248529 A CN201910248529 A CN 201910248529A CN 109912603 A CN109912603 A CN 109912603A
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title claims abstract description 128
- 229910052757 nitrogen Inorganic materials 0.000 title claims abstract description 82
- GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 title claims abstract description 55
- 230000000975 bioactive effect Effects 0.000 title claims abstract description 53
- 230000002194 synthesizing effect Effects 0.000 title abstract description 42
- 238000013459 approach Methods 0.000 title abstract 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 168
- -1 silver hexafluoroantimonate Chemical compound 0.000 claims abstract description 96
- 238000000034 method Methods 0.000 claims abstract description 66
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 18
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 8
- 229940079593 drug Drugs 0.000 claims abstract description 8
- 239000011521 glass Substances 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 239000012298 atmosphere Substances 0.000 claims description 43
- MMAGMBCAIFVRGJ-UHFFFAOYSA-J iridium(3+);1,2,3,4,5-pentamethylcyclopenta-1,3-diene;tetrachloride Chemical class 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 43
- 238000004440 column chromatography Methods 0.000 claims description 39
- 238000007112 amidation reaction Methods 0.000 claims description 18
- 230000009435 amidation Effects 0.000 claims description 15
- 239000003153 chemical reaction reagent Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 150000001336 alkenes Chemical class 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical class 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Chemical class CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 2
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 42
- PBQZQTQFQFYBNJ-UHFFFAOYSA-N n-methoxybenzamide Chemical compound CONC(=O)C1=CC=CC=C1 PBQZQTQFQFYBNJ-UHFFFAOYSA-N 0.000 abstract description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 6
- 239000006227 byproduct Substances 0.000 abstract description 3
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 238000006467 substitution reaction Methods 0.000 abstract description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 abstract 1
- MILUBEOXRNEUHS-UHFFFAOYSA-N iridium(3+) Chemical class [Ir+3] MILUBEOXRNEUHS-UHFFFAOYSA-N 0.000 abstract 1
- WQIQNKQYEUMPBM-UHFFFAOYSA-N pentamethylcyclopentadiene Chemical compound CC1C(C)=C(C)C(C)=C1C WQIQNKQYEUMPBM-UHFFFAOYSA-N 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 172
- 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
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 description 64
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 36
- 238000005160 1H NMR spectroscopy Methods 0.000 description 36
- 239000012043 crude product Substances 0.000 description 36
- 239000003208 petroleum Substances 0.000 description 36
- 239000002994 raw material Substances 0.000 description 31
- 238000004293 19F NMR spectroscopy Methods 0.000 description 13
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 10
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 10
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- JNXLTSSPACJLEG-BQYQJAHWSA-N (e)-n-methyl-3-phenylprop-2-enamide Chemical compound CNC(=O)\C=C\C1=CC=CC=C1 JNXLTSSPACJLEG-BQYQJAHWSA-N 0.000 description 2
- CWIAOSJDTXVSSA-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]-4,5-dihydro-1,3-oxazole Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=NCCO1 CWIAOSJDTXVSSA-UHFFFAOYSA-N 0.000 description 2
- XBHOUXSGHYZCNH-UHFFFAOYSA-N 2-phenyl-1,3-benzothiazole Chemical compound C1=CC=CC=C1C1=NC2=CC=CC=C2S1 XBHOUXSGHYZCNH-UHFFFAOYSA-N 0.000 description 2
- AOVOPXJEOAMRMY-UHFFFAOYSA-N 3-(difluoromethyl)-n-methoxy-1-methylpyrazole-4-carboxamide Chemical compound CONC(=O)C1=CN(C)N=C1C(F)F AOVOPXJEOAMRMY-UHFFFAOYSA-N 0.000 description 2
- AMELKRLHOQGFSI-UHFFFAOYSA-N 3-amino-n-methylbutanamide Chemical compound CNC(=O)CC(C)N AMELKRLHOQGFSI-UHFFFAOYSA-N 0.000 description 2
- BJATUPPYBZHEIO-UHFFFAOYSA-N 3-methyl-2-phenylpyridine Chemical compound CC1=CC=CN=C1C1=CC=CC=C1 BJATUPPYBZHEIO-UHFFFAOYSA-N 0.000 description 2
- MTLFMNFAALESGJ-UHFFFAOYSA-N 5-methoxy-3-methyl-1-phenylpyrazole Chemical compound COC1=CC(C)=NN1C1=CC=CC=C1 MTLFMNFAALESGJ-UHFFFAOYSA-N 0.000 description 2
- AHKXGLRKPKMGTP-UHFFFAOYSA-N N-phenylmethoxyoctadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NOCC1=CC=CC=C1 AHKXGLRKPKMGTP-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- JAWGVVJVYSANRY-UHFFFAOYSA-N cobalt(3+) Chemical compound [Co+3] JAWGVVJVYSANRY-UHFFFAOYSA-N 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 229910052741 iridium Inorganic materials 0.000 description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 2
- GGLGESNCXBFOSN-UHFFFAOYSA-N n-methoxy-2-phenylacetamide Chemical compound CONC(=O)CC1=CC=CC=C1 GGLGESNCXBFOSN-UHFFFAOYSA-N 0.000 description 2
- CZRZGHLNUUOGNL-UHFFFAOYSA-N n-phenylmethoxybutanamide Chemical compound CCCC(=O)NOCC1=CC=CC=C1 CZRZGHLNUUOGNL-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- FRYZFIKPCCCDCD-UHFFFAOYSA-N 2-(2-chlorophenyl)pyridine Chemical compound ClC1=CC=CC=C1C1=CC=CC=N1 FRYZFIKPCCCDCD-UHFFFAOYSA-N 0.000 description 1
- AUWGCKQDHVHZJG-UHFFFAOYSA-N 2-amino-n-methoxyacetamide Chemical compound CONC(=O)CN AUWGCKQDHVHZJG-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- TXDBDBSTXWITQA-UHFFFAOYSA-N 3-amino-N-methoxypropanamide Chemical compound CONC(=O)CCN TXDBDBSTXWITQA-UHFFFAOYSA-N 0.000 description 1
- IJUCBGPQWGGYBV-UHFFFAOYSA-N 4-amino-n-methylbutanamide Chemical compound CNC(=O)CCCN IJUCBGPQWGGYBV-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical class CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- FGHAZDVJHATENE-UHFFFAOYSA-N [N-]=[N+]=[N-].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[NH6+3] Chemical compound [N-]=[N+]=[N-].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[NH6+3] FGHAZDVJHATENE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000015250 liver sausages Nutrition 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- LFJJTHGQRVVGGN-UHFFFAOYSA-N methyl 3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2N=C(ON=2)C=2C(=CC=CC=2)F)=C1 LFJJTHGQRVVGGN-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- BMBFKPBHUSWJPD-UHFFFAOYSA-N n-methoxy-3-(trifluoromethyl)benzamide Chemical compound CONC(=O)C1=CC=CC(C(F)(F)F)=C1 BMBFKPBHUSWJPD-UHFFFAOYSA-N 0.000 description 1
- OVULJVYRDCLMGQ-UHFFFAOYSA-N n-methoxyfuran-2-carboxamide Chemical compound CONC(=O)C1=CC=CO1 OVULJVYRDCLMGQ-UHFFFAOYSA-N 0.000 description 1
- WUELPSVXUUGQFI-UHFFFAOYSA-N n-phenylmethoxycyclopropanecarboxamide Chemical compound C1CC1C(=O)NOCC1=CC=CC=C1 WUELPSVXUUGQFI-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a kind of practical approaches for using N- methoxyamide as nitrogen source synthesizing new bioactive molecule, nitrogen heterocyclic, dichloro (pentamethylcyclopentadiene base) iridium (III) dimer, silver hexafluoroantimonate and the N- methoxy benzamide of aryl substitution are sequentially added in glass reaction tube, with 1,2- dichloroethanes is as solvent, it is reacted at 120 DEG C -140 DEG C, acquisition uses N- methoxyamide as nitrogen source synthesizing new bioactive molecule.The product types multiplicity that benefit is obtained by the present invention not only may be directly applied to the synthesis of drug molecule, modify but also can be used for other further reactions；Meanwhile synthetic route is easy safely, cost is relatively low, operation and last handling process are simple, selectivity is good, methanol is unique by-product, meets the concept of Green Chemistry.
Description
Technical Field
The present invention relates to a practical method for the synthesis of novel biologically active molecules using N-methoxyamides as nitrogen source.
Background
The construction of the C-N bond is one of the most basic operations in nature and organic synthesis, and the resulting amino compound is widely present in natural products, drugs, and functional materials. Conventional synthetic methods use functionalized compounds such as alkenyl or aryl halides to react with a nitrogen source, and the like.
In the prior art, a large number of documents report amidation reactions of C-H bonds, and the construction of C-N bonds. For example, the documents (1) Younoku Park, Kyung Tae Park, Jeung Gon Kim, and SukbokChang. mechanical students on the Rh (III) -Mediated Amidon transfer leader to route C-H amplification with a New Type of amplitude J.Amidon.Chem.Soc.2015, 137, 4534-4542. (2) Ruhuai Mei, Joachim Loup, and AndLutz Acker. Oxazolinyl-amplified C-H amplification by Cobalt (III) catalysis, AC 2016,6,793-797.(3) Jaeyun Ryu, Jengu Kyun, Mkawang K, summer warp cement, arm K, III-branched C-H amplification, and III: an effective use of Acyl Azides as the Nitrogen Source.J. am. chem. Soc.2013,135,12861-12868 (4), Pitabambar Pate and Sukbok Chang. cobalt (III) -catalysis C-HAmidation of aryl using acetyl amides as the convention Amino Source undersurface Condition ACS Cat. 2015,5, 853-.
The synthetic route is as follows:
in the technical scheme, the azide nitrogen source has certain danger in use and is inconvenient to store. The synthesis route of the 1,4, 2-bisoxazole-5-ketone amidation test is complicated, and the substrate has certain limitation. Therefore, there is a need to develop a new amidation reagent which is easy to synthesize, store, obtain raw materials and have a wide variety, and the amidation reaction is applied to the synthesis, modification and modification of drug molecules.
Disclosure of Invention
The invention aims to provide a preparation method of aryl-substituted nitrogen heterocyclic compound ortho-amidation product, which is simple and convenient to operate.
The technical scheme of the invention is as follows:
a practical method for the synthesis of novel biologically active molecules using N-methoxyamides as nitrogen sources, which method comprises:
adding an aryl-substituted nitrogen heterocyclic compound, dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, silver hexafluoroantimonate and an amidation reagent into a glass reaction tube in sequence, reacting at 120-140 ℃ by taking 1, 2-dichloroethane as a solvent, fixing the glass reaction tube in a heating stirrer for stirring, and performing column chromatography separation and purification treatment on a product after the reaction is finished to obtain the novel bioactive molecule synthesized by taking N-methoxyamide as a nitrogen source.
Further, the amidation reagent is represented by the following structural general formula:
wherein,
R1is methyl;
R2、R3、R4、R5any one or two of the above-mentioned two compounds are one or two of hydrogen, alkyl, alkoxy, trifluoromethyl and halogen;
R6is benzyl or methyl;
R7is any one of branched alkyl, cycloalkyl and olefin derivatives, or methylamino protected by phthaloyl and derivatives thereof, or precursors of drug molecules, or any one of benzyl, phenethyl and derivatives thereof, and furan.
Further, the aryl-substituted nitrogen heterocyclic compound is shown as the following structural general formula:
wherein,
R8is any one of hydrogen, methyl, methoxy, carbobenzoxy, trifluoromethyl, X ═ O or N;
R9is any one of alkyl, hydrogen, methyl, methoxyl, carbobenzoxy and trifluoromethyl;
R10is any one of hydrogen, methyl, methoxyl, carbobenzoxy and trifluoromethyl;
R11is any one of hydrogen, methyl, methoxy, carbobenzoxy, trifluoromethyl, X ═ O or N;
R12is hydrogen, methyl or methoxyAny one of benzyloxycarbonyl and trifluoromethyl;
R13is H or F;
R14is acetyl.
Further, the molar ratio of the aryl-substituted nitrogen heterocyclic compound to the dichloro (pentamethylcyclopentadienyl) iridium (III) dimer to the silver hexafluoroantimonate to the amidation reagent is 1: 0.025-0.030:0.1-0.15: 1.5-2.0.
Further, the molar ratio of the aryl-substituted nitrogen heterocyclic compound to the dichloro (pentamethylcyclopentadienyl) iridium (III) dimer to the silver hexafluoroantimonate to the amidation reagent is 1: 0.025: 0.1: 1.5.
further, the concentration of the 1, 2-dichloroethane is 0.2 mmol/mL.
Further, the reaction atmosphere is a reaction in an air atmosphere.
Further, the reaction atmosphere is N2And (4) carrying out a reaction.
Further, the rotating speed of the heating stirrer is 400-800rpm, the heating temperature is 120-140 ℃, and the reaction time is 12-24 h.
The invention provides a practical method for synthesizing novel bioactive molecules by using N-methoxyamide as a nitrogen source, which has the advantages that:
1. the amidation reagent used in the invention takes acids (such as benzoic acid, phenylacetic acid, styrene acid, alkyl acid, amino acid derivatives and the like) as starting materials, and the raw materials are easy to obtain and have a plurality of varieties;
2. the products obtained by the method of the invention have various types, can be directly applied to synthesis, modification and coupling of related drug molecules, enrich the development of the C-N bond research field and have great potential value;
3. the method has the advantages of simple and easy operation of reaction conditions, simple post-treatment process and less byproducts;
4. the invention has important practical significance for enriching the structures of some drug molecules.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments in order to make the above objects, features and advantages more apparent and understandable.
The present invention provides a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, comprising: an aryl-substituted nitrogen heterocyclic compound, dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, silver hexafluoroantimonate and an amidation reagent are sequentially added into a glass reaction tube, 1, 2-dichloroethane is used as a solvent, and the N is used or added under the air atmosphere2Protecting, reacting at 120-140 ℃, fixing the glass reaction tube in a heating stirrer for stirring, and performing column chromatography separation and purification treatment on a product after the reaction is finished, thereby obtaining the novel bioactive molecule.
The reaction process of the above technical scheme can be expressed as follows:
in order to make the aforementioned objects, features and advantages of the present invention more comprehensible, embodiments accompanying the present invention are further described below. The invention is not limited to the embodiments listed but also comprises any other known variations within the scope of the invention as claimed.
Reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic may be included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
Example 1
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: 3-methyl-2-phenylpyridine and N-methoxybenzamide are used as raw materials, and the reaction formula is as follows:
⑴ A reaction tube was charged with 0.0338 g (0.2mmol) of 3-methyl-2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.045 g (0.3mmol) of N-methoxybenzamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 96%).
1H NMR(400MHz,CDCl3)δ13.45(s,1H),8.94–8.63(m,1H),8.44(s,1H),8.05(dd,J＝7.6,1.8Hz,2H),7.69–7.56(m,3H),7.55–7.47(m,3H),7.47–7.40(m,1H),7.22–7.10 (m,1H),2.35(s,3H)；13C NMR(101MHz,CDCl3)δ165.5,155.4,147.4,138.5,138.1,135.8,131.8,131.5,129.8,128.6,128.5,127.4,125.4,123.5,122.4,121.7,18.2.
Example 2
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the aryl-substituted nitrogen heterocyclic compound and 2-chloro-4-methylsulfonyl-N-methoxy benzamide are taken as raw materials, and the reaction formula is as follows:
⑴ A reaction tube was charged with 0.0379 g (0.2mmol) of 2- (2-chlorophenyl) pyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0789 g (0.3mmol) of 2-chloro-4-methylsulfonyl-N-methoxybenzamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 70%).
1H NMR(400MHz,CDCl3)δ9.98(s,1H),8.51(d,J＝4.0Hz,1H),8.26(d,J＝7.7Hz,1H),7.93(s,1H),7.84(t,J＝7.5Hz,2H),7.67(dd,J＝10.6,8.3Hz,2H),7.44–7.28(m,3H),3.05(s,3H)；13C NMR(101MHz,CDCl3)δ163.1,154.3,149.0,143.3,140.4,137.2,136.5,133.0,132.1,131.1,130.1,129.5,129.4,127.7,127.0,126.0,123.3,121.8,44.4；HRMSCalcd for C19H14Cl2N2O3S[M+Na+]:443.0000,Found:443.0013.
Example 3
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: 2-phenylpyridine and N- (benzyloxy) undec-10-enamide are taken as raw materials, and the reaction formula is as follows:
⑴ into a reaction tube were added 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0867 g (0.3mmol) of N- (benzyloxy) undec-10-enamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 48%).
1H NMR(400MHz,CDCl3)δ12.09(s,1H),8.64–8.63(m,1H),8.56(d,J＝8.2Hz,1H),7.84(td,J＝7.9,1.8Hz,1H),7.73(d,J＝8.1Hz,1H),7.64(dd,J＝7.9,1.4Hz,1H),7.44–7.36(m,1H),7.30–7.26(m,1H),7.15(td,J＝7.7,1.1Hz,1H),5.87–5.73(m,1H),5.04–4.90(m,2H),2.38(t,J＝7.6Hz,2H),2.05–2.00(m,2H),1.76–1.67(m,2H),1.39–1.30(m,5H),1.30–1.23(m,5H)；13C NMR(101MHz,CDCl3)δ171.9,158.5,147.5,139.3,137.8,137.8,130.2,128.9,125.8,123.5,123.3,122.1,122.0,114.3,38.7,33.9,29.5,29.4,29.3,29.2, 29.0,25.8；HRMS Calcd for C22H28N2O[M+H+]:337.2280,Found:337.2279.
Example 4
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the aryl-substituted nitrogen heterocyclic compound and N-methoxyl-4-hexadienyl formamide are used as raw materials, and the reaction formula is as follows:
⑴ into a reaction tube were charged 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0423 g (0.3mmol) of N-methoxy-4-hexadienecarboxamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (50% yield).
1H NMR(400MHz,CDCl3)δ12.33(s,1H),8.70–8.62(m,2H),7.93–7.78(m,1H), 7.75(d,J＝8.1Hz,1H),7.66(dd,J＝7.9,1.4Hz,1H),7.49–7.37(m,1H),7.36–7.27(m, 2H),7.25–7.13(m,1H),6.34–6.20(m,1H),6.19–6.05(m,1H),5.94(d,J＝15.0Hz,1H), 1.86(d,J＝6.7Hz,3H),13C NMR(101MHz,CDCl3)δ164.8,158.4,147.3,141.5,138.0, 138.0,130.2,123.0,128.9,125.5,123.6,123.5,123.2,122.1,122.0,18.8.
Example 5
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the method takes 2-phenylpyridine and N-methoxy-p- (dipropyl sulfamic acid) benzamide as raw materials, and has the following reaction formula:
⑴ into a reaction tube were added 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0942 g (0.3mmol) of N-methoxy-p- (dipropylsulfonic acid) benzamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (50% yield).
1H NMR(400MHz,CDCl3)δ13.60(s,1H),8.77(dd,J＝8.3,1.0Hz,1H),8.66–8.62(m,1H),8.17–8.12(m,2H),7.97–7.92(m,2H),7.91–7.80(m,2H),7.76(dd,J＝7.9,1.5 Hz,1H),7.51–7.45(m,1H),7.35–7.29(m,1H),7.23(td,J＝7.9,1.2Hz,1H),3.48–2.83 (m,4H),1.64–1.50(m,4H),0.88(t,J＝7.4Hz,6H)；13C NMR(101MHz,CDCl3)δ164.1, 158.2,147.3,143.0,139.4,138.2,137.9,130.5,128.9,128.2,127.4,125.5,124.2,123.1,122.4, 121.9,50.1,22.1,11.3；HRMS Calcd for C24H27N3O3S[M+Na+]:460.1617,Found:460.1630.
Example 6
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the reaction formula of the compound is as follows, wherein 2-phenylpyridine and 3- (difluoromethyl) -N-methoxyl-1-methyl-1H-pyrazole-4-formamide are used as raw materials:
⑴ A reaction tube was charged with 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0615 g (0.3mmol) of 3- (difluoromethyl) -N-methoxy-1-methyl-1H-pyrazole-4-carboxamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain the desired product (yield 45%).
1H NMR(400MHz,CDCl3)δ12.84(s,1H),8.66–8.46(m,2H),7.87–7.73(m,3H), 7.67(dd,J＝7.9,1.4Hz,1H),7.45–7.36(m,1H),7.34–7.27(m,1H),7.20–7.12(m,1H), 3.98(s,3H)；13C NMR(101MHz,CDCl3)δ159.8,158.3,147.1,146.3(t,JC–F＝24.0Hz), 138.1,137.6,131.0,130.3,128.9,125.3,123.8,123.2,122.2,122.1,118.4(t,JC–F＝3.5Hz), 109.6(t,JC–F＝236.3Hz),39.9；19F NMR(376MHz,CDCl3)δ-115.17(d,J＝54.2Hz)；HRMS Calcd forC17H14F2N4O[M+Na+]:350.1033,Found:350.1037.
Example 7
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the reaction formula of the compound takes 2-phenylpyridine and 3-amino-N-methoxypropionamide protected by phthalic anhydride as raw materials, and comprises the following steps:
⑴ into a reaction tube were added 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0744 g (0.3mmol) of phthalic anhydride-protected 3-amino-N-methoxypropionamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 10:1) to obtain the desired product (yield 72%).
1H NMR(400MHz,CDCl3)δ12.27(s,1H),8.60–8.54(m,1H),8.43(d,J＝8.2Hz,1H),7.79–7.69(m,3H),7.66–7.59(m,3H),7.55(dd,J＝7.9,1.2Hz,1H),7.32(t,J＝7.8Hz,1H),7.22–7.15(m,1H),7.08(t,J＝7.6Hz,1H),4.03(t,J＝7.6Hz,2H),2.74(t,J＝7.4Hz,2H)；13C NMR(101MHz,CDCl3)δ168.4,168.2,157.7,147.0,138.4,137.3,134.0,132.2,130.4,128.9,125.6,124.0,123.4,123.3,122.6,122.2,36.6,34.6；HRMS Calcd forC22H17N3O3[M+Na+]:394.1168,Found:394.1179.
Example 8
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the method takes 2-phenylpyridine and 4-amino-N-methylbutanamide protected by phthalic anhydride as raw materials, and has the following reaction formula:
⑴ into a reaction tube were added 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0786 g (0.3mmol) of phthalic anhydride-protected 4-amino-N-methylbutanamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 10:1) to obtain the desired product (yield 59%).
1H NMR(400MHz,CDCl3)δ12.11(s,1H),8.54(d,J＝4.4Hz,1H),8.38(d,J＝8.2Hz,1H),7.79–7.69(m,3H),7.68–7.57(m,3H),7.54(d,J＝7.8Hz,1H),7.27(t,J＝7.8Hz, 1H),7.19(t,J＝6.1Hz,1H),7.05(t,J＝7.5Hz,1H),3.71(t,J＝6.8Hz,2H),2.38(t,J＝7.6 Hz,2H),2.18–1.97(m,2H)；13C NMR(101MHz,CDCl3)δ170.3,168.4,158.2,147.4,138.0,137.6,134.0,132.2,130.1,128.9,125.6,123.6,123.3,123.2,122.1,122.0,37.6,35.7,24.6；HRMS Calcd for C23H19N3O3[M+Na+]:408.1324,Found:408.1324.
Example 9
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the method takes 2-phenylpyridine and 3- (aminomethyl) -N-methoxyl-5-methylhexanamide protected by phthalic anhydride as raw materials, and has the following reaction formula:
⑴ A reaction tube was charged with 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0954 g (0.3mmol) of phthalic anhydride-protected 3- (aminomethyl) -N-methoxy-5-methylhexanamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours in an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain the desired product (yield 76%).
1H NMR(400MHz,CDCl3)δ12.10(s,1H),8.66(dd,J＝4.9,0.9Hz,1H),8.29(d,J＝8.2Hz,1H),7.84(td,J＝8.0,1.8Hz,1H),7.71(dd,J＝5.4,3.0Hz,3H),7.62–7.56(m,3H),7.33–7.17(m,2H),7.07(td,J＝7.8,1.2Hz,1H),3.84–3.42(m,2H),2.72–2.56(m,1H),2.43–2.26(m,2H),1.91–1.64(m,1H),1.37–1.14(m,2H),0.88(dd,J＝10.0,6.6Hz, 6H)；13CNMR(101MHz,CDCl3)δ170.3,168.7,158.2,147.5,137.9,137.5,133.8,132.1, 130.0,128.7,125.5,123.4,123.2,123.1,122.0,121.9,42.3,42.0,33.1,25.4,23.0, 22.5；HRMSCalcd for C27H28N3O3[M+Na+]:464.1950,Found:464.1931.
Example 10
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the aryl-substituted nitrogen heterocyclic compound and phthalic anhydride protected 2- (1- (aminomethyl) cyclohexyl) -N-methoxy acetamide are used as raw materials, and the reaction formula is as follows:
⑴ into a reaction tube were added 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0990 g (0.3mmol) of phthalic anhydride-protected 2- (1- (aminomethyl) cyclohexyl) -N-methoxyacetamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain the desired product (yield 86%).
1H NMR(400MHz,CDCl3)δ12.01(s,1H),8.58–8.52(m,1H),8.48(dd,J＝8.3,0.7Hz,1H),7.81–7.73(m,3H),7.69–7.64(m,3H),7.58(dd,J＝7.9,1.2Hz,1H),7.34(t,J＝7.8Hz,1H),7.23–7.16(m,1H),7.11(t,J＝7.6Hz,1H),3.83(s,2H),2.45(s,2H),1.72–1.65(m,2H),1.64–1.55(m,2H),1.53–1.31(m,5H),1.30–1.23(m,1H)；13C NMR(101 MHz,CDCl3)δ169.6,169.2,158.2,147.4,137.6,137.4,133.9,132.0,129.9,128.8,126.0,123.4,123.2,123.1,122.1,121.8,46.2,44.6,39.1,33.4,25.6,21.7；HRMS Calcd forC28H27N3O3[M+Na+]:476.1950,Found:476.1931.
Example 11
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: 2-phenyl pyridine and phthalic anhydride protected 2-amino-N-methoxy acetamide are used as raw materials, and the reaction formula is as follows:
⑴ A reaction tube was charged with 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0702 g (0.3mmol) of phthalic anhydride-protected 2-amino-N-methoxyacetamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours in an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 10:1) to obtain the desired product (yield 70%).
1H NMR(400MHz,CDCl3)δ12.54(s,1H),8.52(d,J＝7.7Hz,1H),8.15–8.12(m,1H),7.92(dd,J＝5.5,3.1Hz,2H),7.83–7.76(m,3H),7.72(d,J＝8.1Hz,1H),7.63(dd,J＝7.9,1.4Hz,1H),7.42–7.33(m,1H),7.18–7.09(m,2H),4.54(s,3H)；13C NMR(101MHz, CDCl3)δ167.8,164.7,157.9,146.9,138.3,137.0,134.4,132.3,130.4,129.0,125.8,124.3,123.8,123.3,122.5,122.1,41.9；HRMS Calcd for C21H15N3O3[M+Na+]:380.1001,Found:380.0992.
Example 12
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the method takes 2-phenylpyridine and 3-amino-N-methoxyl-5-methylhexanamide protected by phthalic anhydride as raw materials, and has the following reaction formula:
⑴ into a reaction tube were added 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0912 g (0.3mmol) of phthalic anhydride-protected 3-amino-N-methoxy-5-methylhexanamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain the desired product (yield 78%).
1H NMR(400MHz,CDCl3)δ12.25(s,1H),9.26–8.56(m,1H),8.39(d,J＝8.2Hz,1H),7.71(td,J＝8.1,1.8Hz,1H),7.64–7.61(m,2H),7.59–7.48(m,4H),7.28–7.17(m,2H),7.07–6.98(m,1H),4.98–4.68(m,1H),3.10(dd,J＝14.7,9.0Hz,1H),2.77(dd,J＝14.7,6.0Hz,1H),2.26–2.03(m,1H),1.72–1.29(m,2H),0.85(d,J＝6.2Hz,3H),0.79(d,J＝6.3Hz,3H)；13C NMR(101MHz,CDCl3)δ168.5,168.4,158.0,147.6,137.8,137.4,133.8,131.8,130.1,128.7,1255,123.6,123.2,122.8,122.1,122.0,47.1,41.4,41.2,25.2,23.3；HRMSCalcd for C26H25N3O3[M+Na+]:450.1791,Found:450.1791.
Example 13
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the method takes 2-phenylpyridine and 3-amino-N-methylbutanamide protected by phthalic anhydride as raw materials, and has the following reaction formula:
⑴ into a reaction tube were added 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0786 g (0.3mmol) of phthalic anhydride-protected 3-amino-N-methylbutanamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 95%).
1H NMR(400MHz,CDCl3)δ12.38(s,1H),8.74–8.73(m,1H),8.49(d,J＝8.2Hz,1H),7.82–7.76(m,1H),7.75–7.71(m,2H),7.68–7.57(m,4H),7.36–7.23(m,2H),7.10(t,J＝7.6Hz,1H),5.08–4.85(m,1H),3.22(dd,J＝14.8,8.5Hz,1H),2.91(dd,J＝14.8,6.5Hz,1H),1.53(d,J＝7.0Hz,3H)；13C NMR(101MHz,CDCl3)δ168.4,168.2,158.0(s),147.6,137.7,137.4,133.8,131.9,130.0,128.6,125.3,123.5,123.1,122.7,121.9,44.3,42.0,18.8；HRMS Calcd for C23H19N3O3[M+Na+]:408.1324,Found:408.1312.
Example 14
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: starting from (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate and phthalic anhydride protected 2- (1- (aminomethyl) cyclohexyl) -N-methoxyacetamide, the reaction is as follows:
⑴ A reaction tube was charged with 0.0944 g (0.2mmol) of (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyldiacetic acid ester, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0990 g (0.3mmol) of phthalic anhydride-protected 2- (1- (aminomethyl) cyclohexyl) -N-methoxyacetamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain the desired product (yield 65%).
1H NMR(400MHz,CDCl3)δ12.99(s,1H),9.15(dd,J＝8.8,6.7Hz,1H),8.91(s,1H),8.49(dd,J＝12.0,2.4Hz,1H),8.32(s,1H),7.80–7.75(m,2H),7.72–7.67(m,2H),7.00–6.81(m,1H),6.28(d,J＝5.0Hz,1H),6.00(t,J＝5.3Hz,1H),5.69(t,J＝5.1Hz,1H),4.50–4.44(m,2H),4.39(dd,J＝12.3,4.7Hz,1H),3.87(s,2H),2.54(s,2H),2.16(s,3H),2.12(s,3H),2.09(s,3H),1.76(d,J＝9.7Hz,2H),1.65(s,2H),1.57–1.40(m,5H),1.24(s,1H)；13CNMR(101MHz,CDCl3)δ170.4,170.3,169.7,169.5,169.3,163.6,155.8,151.9,150.8,142.8, 141.9(d,JC–F＝12.4Hz),135.4(d,JC–F＝9.8Hz),134.1,132.1,131.3,123.3,116.8(d,JC–F＝ 2.9Hz),110.2(d,JC–F＝22.5Hz),108.4(d,JC–F＝28.1Hz),86.8,80.5,73.2,70.6,63.1,46.2, 44.8,39.3,33.8,25.8,21.9,20.9,20.6,20.5；19F NMR(376MHz,CDCl3)δ-94.05–-117.39 (m).HRMS Calcd for C33H33FN6O7[M+Na+]:667.3392,Found:667.2297.
Example 15
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: starting from (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate and N-methoxybenzamide, the reaction is as follows:
⑴ (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate 0.0944 g (0.2mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer 0.0040 g (0.005mmol), silver hexafluoroantimonate 0.0069 g (0.02mmol), phthalic anhydride-protected 3- (aminomethyl) -N-methoxy-5-methylhexanamide 0.0954 g (0.3mmol), and 1.00mL of 1, 2-dichloroethane were charged into a reaction tube and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 3:1) to obtain the desired product (yield 52%).
1H NMR(400MHz,CDCl3)δ12.98(s,1H),9.11(dd,J＝9.0,6.6Hz,1H),9.02(s,1H),8.32(s,1H),8.17(dd,J＝12.1,2.7Hz,1H),7.64–7.59(m,2H),7.57–7.50(m,2H),6.86–6.77(m,1H),6.32(d,J＝5.3Hz,1H),6.01(t,J＝5.4Hz,1H),5.70(t,J＝5.0Hz,1H),4.53–4.46(m,2H),4.42(dd,J＝12.4,4.7Hz,1H),3.75–3.65(m,1H),3.65–3.60(m,1H),2.85–2.71(m,1H),2.64–2.29(m,3H),2.17(s,2H),2.15(s,3H),2.10(s,3H),1.78(dt,J＝13.4,6.7Hz,1H),1.30(t,J＝7.2Hz,2H),0.96(d,J＝6.5Hz,3H),0.93(d,J＝6.5Hz,3H)；13C NMR(101MHz,CDCl3)δ170.8,170.4,169.7,169.5,168.7,164.64(d,JC–F＝251.4Hz), 155.8,152.0,150.9,142.7,141.8(d,JC–F＝12.5Hz),135.3(d,JC–F＝10.2Hz),133.9,131.9,131.2,123.1,116.6,110.0(d,JC–F＝22.0Hz),107.9(d,JC–F＝27.9Hz),86.7,80.6,73.2,70.7, 63.2,42.6,42.4,32.8,25.5,22.9,22.6,20.9,20.7,20.5；19F NMR(376MHz,CDCl3)δ-105.02 –-105.11(m).HRMS Calcd for C38H39FN6O10[M+Na+]:781.2609,Found:781.2611.
Example 16
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: starting from (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate and N- (benzyloxy) undec-10-enamide, the reaction is as follows:
⑴ (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate 0.0944 g (0.2mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer 0.0040 g (0.005mmol), silver hexafluoroantimonate 0.0069 g (0.02mmol), N- (benzyloxy) undec-10-enamide 0.0867 g (0.3mmol) and 1.00mL of 1, 2-dichloroethane were charged into a reaction tube and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 43%).
1H NMR(400MHz,CDCl3)δ12.99(s,1H),9.19(dd,J＝9.0,6.6Hz,1H),8.97(s,1H),8.58(dd,J＝12.0,2.6Hz,1H),8.31(s,1H),7.06–6.84(m,1H),6.29(d,J＝5.1Hz,1H),6.01(t,J＝5.3Hz,1H),5.85–5.73(m,1H),5.69(t,J＝5.1Hz,1H),5.12–4.81(m,2H),4.53–4.48(m,1H),4.48–4.38(m,2H),2.47(t,J＝7.6Hz,2H),2.17(s,3H),2.14(s,3H),2.10(s,3H),2.05–1.98(m,2H),1.83–1.73(m,2H),1.42–1.32(m,5H),1.30–1.25(m,5H)；13C NMR(101MHz,CDCl3)δ172.4,170.4,169.7,169.5,165.0(d,JC–F＝251.6Hz),156.0,152.0,150.7,142.8.0,142.1(d,JC–F＝12.5Hz),139.3,135.5(d,JC–F＝10.3Hz),131.4,116.8(d,JC–F＝2.8Hz),114.3(s),110.3(d,JC–F＝22.2Hz),108.5(d,JC–F＝27.9Hz),86.8,80.6,73.2,70.7, 63.2,39.0,33.9,29.5,29.5,29.4,29.2,29.0,25.7,20.9,20.7,20.6；19F NMR(376MHz,CDCl3) δ-104.70(s)；HRMS Calcd for C33H40FN5O8[M+Na+]:676.2759,Found:676.2757.
Example 17
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: starting from (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate and N- (benzyloxy) stearamide, the reaction is as follows:
⑴ (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate 0.0944 g (0.2mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer 0.0040 g (0.005mmol), silver hexafluoroantimonate 0.0069 g (0.02mmol), N- (benzyloxy) stearamide 0.1169 g (0.3mmol) and 1.00mL of 1, 2-dichloroethane were charged into a reaction tube and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain the desired product (yield 53%).
1H NMR(400MHz,CDCl3)δ12.98(s,1H),9.19(dd,J＝9.0,6.6Hz,1H),8.97(s,1H),8.59(dd,J＝12.1,2.7Hz,1H),8.31(s,1H),6.98–6.90(m,1H),6.29(d,J＝5.2Hz,1H),6.01(t,J＝5.4Hz,1H),5.69(t,J＝5.1Hz,1H),4.52–4.48(m,2H),4.41(dd,J＝12.2,4.6Hz,1H),2.47(t,J＝7.6Hz,2H),2.17(s,3H),2.14(s,3H),2.10(s,3H),1.83–1.73(m,2H),1.24(s,28H),0.87(t,J＝6.8Hz,3H)；13C NMR(101MHz,CDCl3)δ172.4,170.4,169.7,169.5,165.0(d,JC–F＝251.5Hz),156.0,152.0,150.7,142.8,142.2(d,JC–F＝12.5Hz),135.5(d,JC–F＝10.2Hz),131.4(s),116.8(t,JC–F＝3.1Hz),110.3(d,JC–F＝22.2Hz),108.5(d, JC–F＝27.8Hz),86.6(s),80.6(s),73.2,70.7,63.2,39.0,32.1,29.8,29.8,29.8,29.7,29.6,29.5, 29.4,25.7,22.8,20.9,20.7,20.6,14.3；19F NMR(376MHz,CDCl3)δ-104.67(s).
Example 18
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: starting from (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate and 4- (N, N-dipropyl) -N-methoxybenzamide, the reaction is as follows:
⑴ (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate 0.0944 g (0.2mmol) (0.2mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer 0.0040 g (0.005mmol), silver hexafluoroantimonate 0.0069 g (0.02mmol), 4- (N, N-dipropyl) -N-methoxybenzamide 0.0942 g (0.3mmol) and 1.00mL of 1, 2-dichloroethane were charged into a reaction tube and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 3:1) to obtain the desired product (yield 47%).
1H NMR(400MHz,CDCl3)δ14.23(s,1H),9.38(dd,J＝9.0,6.5Hz,1H),8.99(s,1H),8.75(dd,J＝11.8,2.6Hz,1H),8.34(s,1H),8.19(d,J＝8.4Hz,2H),7.98(d,J＝8.4Hz,2H),7.18–6.92(m,1H),6.30(d,J＝5.0Hz,1H),6.00(t,J＝5.3Hz,1H),5.68(t,J＝5.1Hz,1H),4.53–4.50(m,1H),4.49–4.39(m,2H),3.19–3.08(m,4H),2.18(s,3H),2.14(s,3H),2.11(s,3H),1.61–1.53(m,4H),0.89(t,J＝7.4Hz,6H)；13C NMR(101MHz,CDCl3)δ170.4, 169.8,169.6,164.6,163.8,155.7,152.2,150.6,143.5,143.0,142.1(d,JC–F＝12.2Hz),139.0,135.9(d,JC–F＝10.6Hz),131.4,128.3,127.6,117.3,111.1(d,JC–F＝21.9Hz),108.7(d,JC–F＝ 27.6Hz),86.9,80.6,73.3,70.7,63.2,50.2,22.1,20.9,20.7,20.6,11.3；19F NMR(377MHz, CDCl3)δ-94.50–-111.96(m)；HRMS Calcd for C35H39FN6O10S[M+Na+]:777.2330,Found: 777.2317.
Example 19
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: starting from (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate and 3- (cyclopropylmethoxy) -4- (difluoromethoxy) -N-methoxybenzamide, the reaction is as follows:
⑴ (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6- (4-fluorophenyl) -9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate 0.0944 g (0.2mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer 0.0040 g (0.005mmol), silver hexafluoroantimonate 0.0069 g (0.02mmol), 3- (cyclopropylmethoxy) -4- (difluoromethoxy) -N-methoxybenzamide 0.0861 g (0.3mmol) and 1.00mL of 1, 2-dichloroethane were charged into a reaction tube and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 3:1) to obtain the desired product (yield 62%).
1H NMR(400MHz,CDCl3)δ14.01(s,1H),9.33(dd,J＝9.0,6.5Hz,1H),9.00(s,1H),8.74(dd,J＝12.0,2.7Hz,1H),8.33(s,1H),7.72(d,J＝2.0Hz,1H),7.62(dd,J＝8.3,2.0Hz, 1H),7.32(d,J＝8.3Hz,1H),7.06–6.95(m,1H),6.75(t,J＝75.0Hz,1H),6.29(d,J＝5.0 Hz,1H),6.00(t,J＝5.3Hz,1H),5.69(t,J＝5.2Hz,1H),4.54–4.48(m,1H),4.49–4.37(m, 2H),4.00(d,J＝6.9Hz,2H),2.18(s,3H),2.14(s,3H),2.11(s,3H),1.33–1.22(m,1H),0.75 –0.61(m,2H),0.43–0.35(m,2H)；13C NMR(101MHz,CDCl3)δ170.4,169.7,169.6,166.3 (d,JC–F＝253.0Hz),165.1,155.9,152.1,150.9,150.6,143.3(t,JC–F＝3.0Hz),143.0,142.4(d, JC–F＝12.4Hz),135.8(d,JC–F＝9.8Hz),133.9,131.4,122.2,119.4,117.2(d,JC–F＝2.8Hz), 116.0(t,JC–F＝261.7Hz),114.5,110.8(d,JC–F＝22.0Hz),108.6(d,JC–F＝28.1Hz),86.9, 80.6,74.3,73.3,70.7,20.9,20.7,20.6,10.2,3.4；19F NMR(376MHz,CDCl3)δ-81.80(s), -104.18(s)；HRMS Calcd for C34H32F3N5O10[M+Na+]:750.1999,Found:750.1997.
Example 20
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: taking (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6-phenyl-9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate and N-methoxybenzamide as raw materials, the reaction formula is as follows:
⑴ into a reaction tube were charged 0.0908 g (0.2mmol) of (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6-phenyl-9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0942 g (0.3mmol) of 4- (N, N-dipropyl) -N-methoxybenzamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 3:1) to obtain the desired product (yield 45%).
1H NMR(400MHz,CDCl3)δ13.78(s,1H),9.15(dd,J＝8.1,1.4Hz,1H),8.98(s,1H),8.83(dd,J＝8.4,0.7Hz,1H),8.34(s,1H),8.16(d,J＝8.5Hz,2H),7.95(d,J＝8.5Hz,2H),7.66–7.48(m,1H),7.39–7.28(m,1H),6.29(d,J＝5.0Hz,1H),6.00(t,J＝5.3Hz,1H), 5.68(t,J＝5.2Hz,1H),4.52–4.44(m,2H),4.40(dd,J＝12.0,4.4Hz,1H),3.24–2.98(m, 4H),2.16(s,3H),2.12(s,3H),2.09(s,3H),1.61–1.48(m,4H),0.88(t,J＝7.4Hz,6H)；13C NMR(101MHz,CDCl3)δ170.4,169.7,169.5,164.3,156.4,152.2,150.6,143.2,143.1,139.5,139.3,133.6,132.6,131.7,128.2,127.5,123.9,121.6,121.4,86.9,80.5,73.2,70.6,63.1,50.1, 22.1,20.9,20.6,20.5,11.3；HRMSCalcd for C35H40N6O10S[M+Na+]:759.2424,Found: 759.2435.
Example 21
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: starting from (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6-phenyl-9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate and 6- (3- ((3S,5S) -adamantan-1-yl) -4-methoxyphenyl) -N-methoxy-2-naphthamide, the reaction scheme is as follows:
⑴ to a reaction tube were added 0.0908 g (0.2mmol) of (2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6-phenyl-9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.1323 g (0.3mmol) of 6- (3- ((3S,5S) -adamantan-1-yl) -4-methoxyphenyl) -N-methoxy-2-naphthamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 3:1) to obtain the desired product (yield 51%).
1H NMR(400MHz,CDCl3)δ13.82(s,1H),9.17(dd,J＝8.0,1.5Hz,1H),9.10(s,1H),8.96(dd,J＝8.4,0.9Hz,1H),8.60(s,1H),8.35(s,1H),8.14(dd,J＝8.6,1.7Hz,1H),8.03(t, J＝8.5Hz,3H),7.84(dd,J＝8.5,1.7Hz,1H),7.67–7.55(m,3H),7.35–7.28(m,1H),7.01 (d,J＝8.5Hz,1H),6.31(d,J＝5.1Hz,1H),6.04(t,J＝5.3Hz,1H),5.72(t,J＝5.2Hz,1H), 4.53–4.48(m,1H),4.48–4.38(m,2H),3.91(s,3H),2.21–2.16(m,11H),2.13(s,3H),2.10 (s,3H),1.82(s,7H)；13C NMR(101MHz,CDCl3)δ169.9,169.1,168.9,165.4,158.4,156.2, 151.6,150.2,142.4,140.5,139.5,138.5,134.9,133.0,132.2,132.0,131.2,131.1,129.0,128.2, 127.4,126.2,125.5,125.3,124.3,123.8122.8,121.1,120.7,111.7,86.2,80.0,72.6,70.1,62.6, 54.7,40.1,36.7,36.7,28.7,20.3,20.1,19.9.
Example 22
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: 2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6-phenyl-9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate and 3- (5- (2-fluorophenyl) -1,2, 4-oxadiazol-3-yl) -N-methoxybenzamide were used as starting materials, and the reaction formula was as follows:
⑴ into a reaction tube were added 0.0908 g (0.2mmol) of 2S,3S,4S,5S) -2- (acetoxymethyl) -5- (6-phenyl-9H-purin-9-yl) tetrahydrofuran-3, 4-diyl diacetate, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0939 g (0.3mmol) of 3- (5- (2-fluorophenyl) -1,2, 4-oxadiazol-3-yl) -N-methoxybenzamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 3:1) to obtain the desired product (yield 47%).
1H NMR(400MHz,CDCl3)δ14.06(s,1H),9.46(s,1H),9.19(d,J＝8.0Hz,1H),8.99(s, 1H),8.92(d,J＝8.3Hz,1H),8.48–8.22(m,4H),7.73–7.52(m,3H),7.44–7.28(m,3H),6.34(d,J＝5.4Hz,1H),6.02(t,J＝5.5Hz,1H),5.65(t,J＝5.4Hz,1H),4.50–4.46(m,1H),4.44–4.36(m,2H),2.16(s,3H),2.13(s,3H),2.07(s,3H)；13C NMR(101MHz,CDCl3)δ 173.2(d,JC–F＝4.4Hz),170.4,169.7,169.5,168.4,164.5,162.2,159.7,156.4,152.3,151.6,142.8,139.9,136.1,134.9(d,JC–F＝8.6Hz),133.6,132.5,131.6,131.5,131.1,130.8,129.7, 127.2,125.4,124.9(d,JC–F＝3.7Hz),123.6,121.6(d,JC–F＝17.4Hz),117.4(d,JC–F＝20.9 Hz),112.9(d,JC–F＝11.3Hz),86.5,80.7,73.2,70.8,63.1,20.9,20.7,20.5；19FNMR(376 MHz,CDCl3)δ-97.68–-130.43(m).
Example 23
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the reaction formula is as follows, wherein the reaction formula is that 3- (5- (2-fluorophenyl) -1,2, 4-oxadiazole-3-yl) methyl benzoate and N-methoxybenzamide are used as raw materials:
⑴ methyl 3- (5- (2-fluorophenyl) -1,2, 4-oxadiazol-3-yl) benzoate 0.0596 g (0.2mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer 0.0040 g (0.005mmol), silver hexafluoroantimonate 0.0069 g (0.02mmol), phthalic anhydride protected 3-amino-N-methylbutyramide 0.0786 g (0.3mmol) and 1.00mL of 1, 2-dichloroethane were charged into a reaction tube and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 3:1) to obtain the desired product (yield 41%).
1H NMR(400MHz,CDCl3)δ10.75(s,1H),8.93(d,J＝2.0Hz,1H),8.74(d,J＝8.9Hz,1H),8.33–8.24(m,1H),8.10(dd,J＝8.8,2.0Hz,1H),7.79(dd,J＝5.4,3.0Hz,2H),7.71–7.62(m,3H),7.45–7.38(m,1H),7.37–7.30(m,1H),5.13–4.92(m,1H),3.93(s,3H),3.43(dd,J＝15.5,8.9Hz,1H),3.05(dd,J＝15.5,5.9Hz,1H),1.59(d,J＝7.0Hz,3H)；13C NMR(101MHz,CDCl3)δ172.13(d,JC–F＝4.8Hz),169.3,168.3,167.4,166.1,162.4,159.8,141.6, 135.5(d,JC–F＝8.9Hz),134.0,133.7,132.1,131.2(d,JC–F＝8.3Hz),125.2,125.1,123.4, 120.5,117.5(d,JC–F＝20.8Hz),113.4,112.1(d,JC–F＝11.0Hz),52.3,44.0,41.9,19.1；19F NMR(376MHz,CDCl3)δ-107.67(s).
Example 24
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the reaction formula is as follows, wherein N, N-dibenzyl-4- (5- (p-tolyl) -3- (trifluoromethyl) -1H-pyrazol-1-yl) benzene sulfonamide and phthalic anhydride protected 3-amino-N-methyl butyramide are used as raw materials:
⑴ into a reaction tube were added 0.1122 g (0.2mmol) of N, N-dibenzyl-4- (5- (p-tolyl) -3- (trifluoromethyl) -1H-pyrazol-1-yl) benzenesulfonamide, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0786 g (0.3mmol) of phthalic anhydride-protected 3-amino-N-methylbutyramide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 3:1) to obtain the desired product (yield 60%).
1H NMR(400MHz,CDCl3)δ8.83(d,J＝1.7Hz,1H),8.75(s,1H),7.69–7.64(m,2H),7.57–7.52(m,2H),7.37(dd,J＝8.4,2.0Hz,1H),7.21–7.19(m,6H),7.14–7.04(m,4H),7.01(d,J＝8.0Hz,2H),6.91–6.89(m,3H),6.81(s,1H),4.93–4.76(m,1H),4.32(s,4H),3.21(dd,J＝15.0,9.4Hz,1H),2.82(dd,J＝15.0,5.7Hz,1H),2.32(s,3H),1.50(d,J＝6.9Hz,3H)；13C NMR(101MHz,CDCl3)δ168.5,168.1,147.0,145.0(q,JC–F＝38.8Hz),141.6,140.0,135.3,133.9,133.8,131.7,131.2,129.8,128.7,128.5,128.4,127.8,127.6,124.8,123.3, 122.7,122.4,105.8,50.7,44.2,41.5,21.4,19.0；19F NMR(376MHz,CDCl3)δ-62.43(s).
Example 25
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the method takes benzyl (3-methyl-1-phenyl-1H-pyrazol-5-yl) carbonate and N-methoxyl (2, 2-difluoro-1, 3-benzodioxole-5-) formamide as raw materials, and has the following reaction formula:
⑴ benzyl (3-methyl-1-phenyl-1H-pyrazol-5-yl) carbonate 0.0616 g (0.2mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer 0.0040 g (0.005mmol), silver hexafluoroantimonate 0.0069 g (0.02mmol), N-methoxy (2, 2-difluoro-1, 3-benzodioxole-5-) formamide 0.0693 g (0.3mmol), and 1.00mL of 1, 2-dichloroethane were charged in a reaction tube, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 10:1) to obtain the desired product (yield 45%).
1H NMR(400MHz,CDCl3)δ10.38(s,1H),8.57(dd,J＝8.3,1.1Hz,1H),7.68–7.56(m,2H),7.43–7.34(m,4H),7.34–7.30(m,3H),7.19–7.08(m,2H),6.19(s,1H),5.19(s,2H),2.40(s,2H)；13C NMR(101MHz,CDCl3)δ163.3,150.7,150.2,146.3,146.0,144.2,133.9,133.0,131.8,131.4,129.3,129.1,128.9,128.8,126.1,124.8,124.1,123.6,122.5,109.4, 109.0,95.6,71.7,14.6；19F NMR(376MHz,CDCl3)δ-49.70(s)；HRMSCalcdfor C26H19F2N3O6[M+Na+]:530.1140,Found:530.1117.
Example 26
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the method takes benzyl (3-methyl-1-phenyl-1H-pyrazol-5-yl) carbonate and 4- (N, N-dipropyl) -N-methoxybenzamide as raw materials, and has the following reaction formula:
⑴ benzyl (3-methyl-1-phenyl-1H-pyrazol-5-yl) carbonate 0.0616 g (0.2mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer 0.0040 g (0.005mmol), silver hexafluoroantimonate 0.0069 g (0.02mmol), 4- (N, N-dipropyl) -N-methoxybenzamide 0.0942 g (0.3mmol) and 1.00mL of 1, 2-dichloroethane were charged in a reaction tube and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 10:1) to obtain the desired product (yield 40%).
1H NMR(400MHz,CDCl3)δ10.54(s,1H),8.59(dd,J＝8.3,1.0Hz,1H),8.00–7.94(m,2H),7.92–7.86(m,2H),7.45–7.39(m,1H),7.38–7.30(m,6H),7.15(td,J＝8.0,1.4 Hz,1H),6.19(s,1H),5.19(s,2H),3.10(dd,J＝8.6,6.8Hz,4H),2.39(s,3H),1.61–1.50(m,4H),0.88(t,J＝7.4Hz,6H)；13C NMR(101MHz,CDCl3)δ163.6,150.7,150.2,145.9,143.4,138.4,133.8,132.8,129.3,129.1,128.9,128.8,128.0,127.4,126.2,124.7,124.3,122.5,95.6 71.7,50.1,22.1,14.7,11.3；HRMS Calcd for C31H34N4O6S[M+Na+]:613.2097,Found: 613.2069.
Example 27
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the method takes benzyl (3-methyl-1-phenyl-1H-pyrazol-5-yl) carbonate and 3- (cyclopropylmethoxy) -4- (difluoromethoxy) -N-methoxybenzamide as raw materials, and has the following reaction formula:
⑴ benzyl (3-methyl-1-phenyl-1H-pyrazol-5-yl) carbonate 0.0616 g (0.2mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer 0.0040 g (0.005mmol), silver hexafluoroantimonate 0.0069 g (0.02mmol), 3- (cyclopropylmethoxy) -4- (difluoromethoxy) -N-methoxybenzamide 0.0861 g (0.3mmol) and 1.00mL of 1, 2-dichloroethane were charged in a reaction tube and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 65%).
1H NMR(400MHz,CDCl3)δ10.19(s,1H),8.57(d,J＝8.0Hz,1H),7.56(d,J＝1.7Hz,1H),7.43–7.35(m,4H),7.34–7.26(m,4H),7.20(d,J＝8.3Hz,1H),7.12(t,J＝7.3Hz, 1H),6.71(t,J＝75.1Hz,1H),6.17(s,1H),5.19(s,2H),3.94(d,J＝7.0Hz,2H),2.38(s,3H),1.35–1.25(m,1H),0.66(q,J＝5.7Hz,2H),0.36(q,J＝4.9Hz,2H)；13C NMR(101MHz, CDCl3)δ164.1,150.8,150.1,145.91,143.2(t,JC–F＝3.1Hz),133.9,133.3,133.2,129.2, 129.2,128.9,128.8,126.2,125.0,124.0,122.5,122.2,119.3,116.0(t,JC–F＝261.6Hz)114.2,95.5,74.3,71.7,14.7,10.2,3.4；19F NMR(376MHz,CDCl3)δ-81.82(s).
Example 28
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: 2-phenylpyridine and N-methoxyl-3-trifluoromethyl benzamide are used as raw materials, and the reaction formula is as follows:
⑴ into a reaction tube were added 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0274 g (0.3mmol) of N-methoxy-3-trifluoromethylbenzamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 86%).
1H NMR(400MHz,CDCl3)δ13.71(s,1H),8.81(dd,J＝8.3,1.1Hz,1H),8.64–8.61(m,1H),8.30(s,1H),8.25(d,J＝7.8Hz,1H),7.86–7.74(m,3H),7.72(dd,J＝7.9,1.5Hz,1H),7.64–7.60(m,1H),7.52–7.41(m,1H),7.29–7.23(m,1H),7.22–7.12(m,1H)；13C NMR(101MHz,CDCl3)δ163.8,158.1,147.1,138.1,136.5,131.2(d,JC–F＝0.9Hz),130.8 (q,JC–F＝32.7Hz),130.40(s),129.4,128.7,128.1(q,JC–F＝3.6Hz),125.4,125.1,124.0(d,JC–F＝0.9Hz),123.9,122.9,122.7,122.3,121.7；19F NMR(376MHz,CDCl3)δ-62.51(s).
Example 29
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: 2-phenylpyridine and N-methoxy furan formamide are used as raw materials, and the reaction formula is as follows:
⑴ A reaction tube was charged with 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0423 g (0.3mmol) of N-methoxyfurancarboxamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 70%).
1H NMR(400MHz,CDCl3)δ13.29(s,1H),8.77–8.68(m,2H),7.88–7.82(m,1H), 7.77(d,J＝8.1Hz,1H),7.71(dd,J＝7.9,1.5Hz,1H),7.56–7.54(m,1H),7.49–7.41(m, 1H),7.33–7.28(m,1H),7.22–7.17(m,2H),6.54(dd,J＝3.5,1.7Hz,1H)；13C NMR(101 MHz,CDCl3)δ158.2,156.7,149.1,147.5,144.4,137.9,137.5,130.3,128.9,125.9,123.8,123.0,122.1,122.1,114.6,112.3
Example 30
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: the reaction formula of the method is as follows by taking 2-phenylpyridine and N- (benzyloxy) butanamide as raw materials:
⑴ into a reaction tube were added 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0579 g (0.3mmol) of N- (benzyloxy) butanamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 70%).
1H NMR(400MHz,CDCl3)δ12.10(s,1H),8.68–8.61(m,1H),8.56(d,J＝8.3Hz,1H),7.83(td,J＝7.8,1.9Hz,1H),7.73(d,J＝8.1Hz,1H),7.64(dd,J＝7.9,1.5Hz,1H),7.45–7.33(m,1H),7.30–7.26(m,1H),7.15(td,J＝7.8,1.2Hz,1H),2.37(t,J＝7.5Hz,2H),1.86–1.65(m,2H),0.98(t,J＝7.4Hz,3H)；13C NMR(101MHz,CDCl3)δ171.8,158.5,147.5,137.8,137.7,130.1,128.93(s),125.8,123.5,123.2,122.1,122.0,40.6,19.1,13.9；HRMSCalcd for C15H16N2O[M+Na+]:263.1160,Found:263.1162.
Example 31
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: taking 2-phenylpyridine and N- (benzyloxy) cyclopropane formamide as raw materials, the reaction formula is as follows:
⑴ into a reaction tube were added 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0573 g (0.3mmol) of N- (benzyloxy) cyclopropanecarboxamide, and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (91% yield).
1H NMR(400MHz,CDCl3)δ12.33(s,1H),8.66–8.65(m,1H),8.54(d,J＝8.2Hz,1H),7.84(td,J＝7.9,1.8Hz,1H),7.74(d,J＝8.1Hz,1H),7.64(dd,J＝7.9,1.4Hz,1H),7.43–7.33(m,1H),7.31–7.26(m,1H),7.16–7.11(m,1H),1.61–1.53(m,1H),1.11–1.01(m, 2H),0.89–0.78(m,2H)；13C NMR(101MHz,CDCl3)δ172.4,158.4,147.3,138.0,137.8, 130.2,129.0,123.4,123.3,122.1,122.0,16.6,7.9；HRMS Calcd for C15H14N2O[M+Na+]:261.1004,Found:261.1011.
Example 32
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: 2-phenylpyridine and N-methoxyl-2-phenylacetamide are taken as raw materials, and the reaction formula is as follows:
⑴ into a reaction tube were added 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0495 g (0.3mmol) of N-methoxy-2-phenylacetamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 79%).
1H NMR(400MHz,CDCl3)δ11.75(s,1H),8.54(d,J＝8.2Hz,1H),8.11(dd,J＝4.9,0.9Hz,1H),7.79–7.71(m,1H),7.61(d,J＝8.1Hz,1H),7.56(dd,J＝7.9,1.5Hz,1H),7.47 –7.36(m,1H),7.37–7.28(m,5H),7.20–7.11(m,2H),3.75(s,2H)；13C NMR(101MHz, CDCl3)δ170.1,158.0,147.5,137.6137.3,134.9,130.9,129.9,129.0,128.9,127.3,126.4,123.8,122.9,122.3,121.6,45.8.
Example 33
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: 2-phenylpyridine and N-methyl cinnamamide are used as raw materials, and the reaction formula is as follows:
⑴ A reaction tube was charged with 0.0310 g (0.2mmol) of 2-phenylpyridine, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0531 g (0.3mmol) of N-methylcinnamamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours in an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 85%).
1H NMR(400MHz,CDCl3)δ12.40(s,1H),8.68–8.57(m,2H),7.86–7.78(m,1H),7.75–7.68(m,1H),7.69–7.58(m,2H),7.49(d,J＝1.3Hz,2H),7.42–7.22(m,5H),7.17–7.09(m,1H),6.51(dd,J＝15.7,5.2Hz,1H)；13C NMR(101MHz,CDCl3)δ164.4,158.2, 147.3,141.1,138.2,137.9,135.0,130.3,129.8,129.0,128.9,128.0,125.7,123.8,123.4,122.8, 122.4,122.1.
Example 34
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: 2-phenyl benzothiazole and N-methoxybenzamide are used as raw materials, and the reaction formula is as follows:
⑴ A reaction tube was charged with 0.0422 g (0.2mmol) of 2-phenylbenzothiazole, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0453 g (0.3mmol) of N-methoxybenzamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 65%).
1H NMR(400MHz,CDCl3)δ13.36(s,1H),9.05(dd,J＝8.5,1.0Hz,1H),8.30–8.20(m,2H),7.98(d,J＝8.1Hz,1H),7.93–7.87(m,2H),7.62–7.58(m,3H),7.56–7.51(m, 2H),7.46–7.40(m,1H),7.23–7.16(m,1H)；13C NMR(101MHz,CDCl3)δ169.2,166.5, 152.9,138.6,135.8,133.5,132.4,132.0,130.0,128.8,128.0,126.9,126.0,123.4,122.4,121.7, 121.0,119.5.
Example 35
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: 1-phenyl-3-methyl-5-methoxy pyrazole and N-methoxy benzamide are used as raw materials, and the reaction formula is as follows:
⑴ A reaction tube was charged with 0.0376 g (0.2mmol) of 1-phenyl-3-methyl-5-methoxypyrazole, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0453 g (0.3mmol) of N-methoxybenzamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 75%).
1H NMR(400MHz,CDCl3)δ10.97(s,1H),8.67(dd,J＝8.3,1.0Hz,1H),8.27–7.89(m,2H),7.60–7.55(m,1H),7.54–7.49(m,3H),7.45–7.36(m,1H),7.21(td,J＝7.9,1.3 Hz,1H),5.61(s,1H),3.93(s,3H),2.41(s,3H)；13C NMR(101MHz,CDCl3)δ165.0,156.6, 149.6,135.0,132.9,131.8,128.7,128.1,127.3,126.8,124.8,123.5,122.5,85.9,59.0,14.5.
Example 36
This example demonstrates a practical method for synthesizing novel bioactive molecules using N-methoxyamide as a nitrogen source, as follows: taking 2- (4- (trifluoromethyl) phenyl) -4, 5-dihydrooxazole and N-methoxybenzamide as raw materials, the reaction formula is as follows:
⑴ into a reaction tube were charged 0.0430 g (0.2mmol) of 2- (4- (trifluoromethyl) phenyl) -4, 5-dihydrooxazole, 0.0040 g (0.005mmol) of dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, 0.0069 g (0.02mmol) of silver hexafluoroantimonate, 0.0453 g (0.3mmol) of N-methoxybenzamide and 1.00mL of 1, 2-dichloroethane, and reacted at 120 ℃ for 12 hours under an air atmosphere;
⑵ TLC tracing the reaction until complete completion;
⑶ the crude product obtained after the reaction was completed was isolated by column chromatography (petroleum ether: ethyl acetate: 15:1) to obtain the desired product (yield 70%).
1H NMR(400MHz,CDCl3)δ13.10(s,1H),9.34(s,1H),8.07(d,J＝7.3Hz,1H),7.98(d,J＝8.2Hz,1H),7.60–7.46(m,2H),7.33(d,J＝8.3Hz,1H),4.46(t,J＝9.6Hz,1H),4.24(t,J＝9.6Hz,1H)；13C NMR(101MHz,CDCl3)δ166.4,164.3,140.7,134.8,134.2(q,JC–F＝32.7Hz),132.2,129.9,128.8,127.9,125.1(q,JC–F＝274.0Hz),118.9(q,JC–F＝3.7Hz),116.9 (q,JC–F＝3.9Hz),116.1(q,JC–F＝1.1Hz),66.7,54.9；19F NMR(376MHz,CDCl3)δ-63.19 (s).
In conclusion, the invention uses benzoyl derivatives as starting materials, has easily obtained raw materials and a plurality of varieties, and provides a novel amidation reagent. Compared with the traditional azide, the compound is convenient to synthesize and store, is safer in use, has wider substrate range compared with a 1,4, 2-bisoxazole-5-ketone amidation reagent, and is closer to an ideal C-H bond amidation reagent. The products obtained by the method of the invention have various types, can be directly applied to the synthesis and modification of drug molecules and can also be used for other further reactions; meanwhile, the synthesis route is safe and easy to implement, the cost is low, the reaction operation and the post-treatment process are simple, the selectivity is good, methanol is the only byproduct, and the concept of green chemistry is met.
It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.
Claims (9)
1. A practical method for the synthesis of novel biologically active molecules using N-methoxyamides as nitrogen sources, comprising: adding an aryl-substituted nitrogen heterocyclic compound, dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, silver hexafluoroantimonate and an amidation reagent into a glass reaction tube in sequence, reacting at 120-140 ℃ by taking 1, 2-dichloroethane as a solvent, fixing the glass reaction tube in a heating stirrer for stirring, and performing column chromatography separation and purification treatment on a product after the reaction is finished to obtain the novel bioactive molecule synthesized by taking N-methoxyamide as a nitrogen source.
2. The practical method of claim 1 for the synthesis of novel bioactive molecules using N-methoxyamide as nitrogen source, characterized in that: the amidation reagent is represented by the following structural general formula:
wherein,
R1is methyl;
R2、R3、R4、R5any one or two of the above-mentioned two compounds are one or two of hydrogen, alkyl, alkoxy, trifluoromethyl and halogen;
R6is benzyl or methyl;
R7is any one of branched alkyl, cycloalkyl and olefin derivatives, or methylamino protected by phthaloyl and derivatives thereof, or precursors of drug molecules, or any one of benzyl, furan, phenethyl and derivatives thereof.
3. The practical method of claim 1 for the synthesis of novel bioactive molecules using N-methoxyamide as nitrogen source, characterized in that: the aryl-substituted nitrogen heterocyclic compound is shown as the following structural general formula:
wherein,
R8is any one of hydrogen, methyl, methoxy, carbobenzoxy, trifluoromethyl, X ═ O or N;
R9is any one of alkyl, hydrogen, methyl, methoxyl, carbobenzoxy and trifluoromethyl;
R10is any one of hydrogen, methyl, methoxyl, carbobenzoxy and trifluoromethyl;
R11is any one of hydrogen, methyl, methoxy, carbobenzoxy, trifluoromethyl, X ═ O or N;
R12is any one of hydrogen, methyl, methoxyl, carbobenzoxy and trifluoromethyl;
R13is H or F;
R14is acetyl.
4. The practical method of claim 1 for the synthesis of novel bioactive molecules using N-methoxyamide as nitrogen source, characterized in that: the molar ratio of the aryl-substituted nitrogen heterocyclic compound to dichloro (pentamethylcyclopentadienyl) iridium (III) dimer to silver hexafluoroantimonate to amidation reagent is 1: 0.025-0.030:0.1-0.15:1.5-2.0.
5. The practical method of claim 4 for the synthesis of novel bioactive molecules using N-methoxyamide as nitrogen source, characterized in that: the molar ratio of the aryl-substituted nitrogen heterocyclic compound to dichloro (pentamethylcyclopentadienyl) iridium (III) dimer to silver hexafluoroantimonate to amidation reagent is 1: 0.025: 0.1: 1.5.
6. the practical method of claim 1 for the synthesis of novel bioactive molecules using N-methoxyamide as nitrogen source, characterized in that: the concentration of the 1, 2-dichloroethane is 0.2 mmol/mL.
7. The practical method of claim 1 for the synthesis of novel bioactive molecules using N-methoxyamide as nitrogen source, characterized in that: the reaction atmosphere is a reaction in an air atmosphere.
8. The practical method of claim 1 for the synthesis of novel bioactive molecules using N-methoxyamide as nitrogen source, characterized in that: the reaction atmosphere is N2And (4) carrying out a reaction.
9. The practical method of claim 1 for the synthesis of novel bioactive molecules using N-methoxyamide as nitrogen source, characterized in that: the rotating speed of the heating stirrer is 400-800rpm, the heating temperature is 120-140 ℃, and the reaction time is 12-24 h.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111978349A (en) * | 2020-09-24 | 2020-11-24 | 温州大学 | Method for synthesizing phosphonimide compound |
| CN111978349B (en) * | 2020-09-24 | 2022-12-09 | 温州大学 | Method for synthesizing phosphonimide compound |
| CN116063209A (en) * | 2023-02-07 | 2023-05-05 | 上海沃凯生物技术有限公司 | Method for preparing benzylamine derivative by catalyzing amination of benzyl C-H bond through nickel under promotion of visible light |
| CN116063209B (en) * | 2023-02-07 | 2024-04-09 | 上海沃凯生物技术有限公司 | Method for preparing benzylamine derivative by catalyzing amination of benzyl C-H bond through nickel under promotion of visible light |
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