CN116813613A - Rhodium-catalyzed method for synthesizing amide compound through pyridine triazole and phenyl isocyanate - Google Patents
Rhodium-catalyzed method for synthesizing amide compound through pyridine triazole and phenyl isocyanate Download PDFInfo
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- CN116813613A CN116813613A CN202310559868.4A CN202310559868A CN116813613A CN 116813613 A CN116813613 A CN 116813613A CN 202310559868 A CN202310559868 A CN 202310559868A CN 116813613 A CN116813613 A CN 116813613A
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- -1 amide compound Chemical class 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 title claims abstract description 19
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 title claims abstract description 17
- JVNIAJRGELYGEG-UHFFFAOYSA-N pyridine;2h-triazole Chemical compound C1=CNN=N1.C1=CC=NC=C1 JVNIAJRGELYGEG-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 14
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 10
- 239000010948 rhodium Substances 0.000 claims abstract description 10
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 238000010499 C–H functionalization reaction Methods 0.000 claims abstract description 7
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 4
- 150000003624 transition metals Chemical class 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
- 238000010898 silica gel chromatography Methods 0.000 claims description 9
- 229910018286 SbF 6 Inorganic materials 0.000 claims description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- 101710134784 Agnoprotein Proteins 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 230000035484 reaction time Effects 0.000 claims 1
- 238000007789 sealing Methods 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 239000012948 isocyanate Substances 0.000 abstract description 3
- 150000002894 organic compounds Chemical class 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 150000003951 lactams Chemical group 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- IHHUGFJSEJSCGE-UHFFFAOYSA-N 1-isocyanato-2-phenylbenzene Chemical compound O=C=NC1=CC=CC=C1C1=CC=CC=C1 IHHUGFJSEJSCGE-UHFFFAOYSA-N 0.000 description 1
- FMDGXCSMDZMDHZ-UHFFFAOYSA-N 1-isocyanato-4-methoxybenzene Chemical compound COC1=CC=C(N=C=O)C=C1 FMDGXCSMDZMDHZ-UHFFFAOYSA-N 0.000 description 1
- WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 1
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 1
- MGYGFNQQGAQEON-UHFFFAOYSA-N 4-tolyl isocyanate Chemical compound CC1=CC=C(N=C=O)C=C1 MGYGFNQQGAQEON-UHFFFAOYSA-N 0.000 description 1
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- AJIZIQCKUSMNPW-UHFFFAOYSA-N chlorobenzene;isocyanic acid Chemical compound N=C=O.ClC1=CC=CC=C1 AJIZIQCKUSMNPW-UHFFFAOYSA-N 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- FQDDBYGPHUUTRN-UHFFFAOYSA-N methyl 4-isocyanatobenzoate Chemical compound COC(=O)C1=CC=C(N=C=O)C=C1 FQDDBYGPHUUTRN-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
The invention relates to a method for synthesizing an amide compound by using a pyridine triazole compound and an isocyanate compound. Transition metal rhodium is used as a catalyst, pyridine triazole compounds and phenyl isocyanate compounds are used as raw materials, and under the condition that silver salt exists, the amide compounds are synthesized through C-H activation. Compared with other methods, the method has simple steps, atomic economy and step economy, is a method for effectively preparing the important amide compounds in the organic compounds, and has important application significance.
Description
Technical Field
The invention relates to a method for synthesizing an important amide compound in an organic compound through a pyridine triazole compound and an isocyanate benzene ester compound, belonging to the field of organic chemical synthesis.
Background
Amide and lactam backbones are a class of structures that are often found in pharmaceutical and natural molecules, and a series of methods have been developed to construct this indispensable amide linkage. In these studies, transition metal-catalyzed C-H activation stands out as a simpler synthetic route, and the unactivated C-H bond can be amidated directly. Many transition metal catalyzed C-H functionalization methods require Directing Groups (DGs), particularly convertible DGs, to improve regioselectivity and utility. By DGs-assisted C-H activation strategy, the C-H bond is reacted with unsaturated polar C-N Direct pi bond addition, selective attachment of nitrogen-based functional groups toAmong the molecules, the most efficient and economical method for rapid synthesis of amides and lactams is provided. Isocyanates have been widely used as multifunctional building blocks in organic synthesis to build C-C bonds into amides. Thus, the use of isocyanate as a functional group would be a more direct method of synthesizing amides. Pyridine triazole has been developed as a powerful tool for synthesizing compounds having the following propertiesNVarious molecules of heterocyclic fragments. Triazolyl as a convertible DG may direct C-H selective activation. Pyridine triazole is an ideal compound for DG related C-H activation and further conversion.
Disclosure of Invention
The invention realizes the method for synthesizing the amide compound by C-H activation by taking pyridine triazole compounds and phenyl isocyanate compounds as raw materials in the presence of a metal rhodium complex catalyst and silver salt. The invention has the advantages of easily obtained raw materials, good substrate applicability, simple and convenient operation, atom economy and wide application prospect.
The chemical reaction formula of the invention is as follows:
，
(1) Pyridine triazole compounds, phenyl isocyanate compounds, catalysts, silver salts and solvents are sequentially added into a clean and dry pressure-resistant bottle, nitrogen is introduced, and the mixture is moved to 100 ℃ and stirred for 12 hours.
(2) After TLC monitoring reaction, spin-drying the solvent, and separating and purifying the residue by silica gel column chromatography to obtain the product.
Pyridine triazole compound in step (1), R 1 Is one or more of hydrogen, C1-C5 alkyl and C1-C5 alkoxy; phenyl isocyanate compound, R 2 Is one or more of hydrogen, C1-C5 alkyl, C1-C5 alkoxy, halogen, nitro, C1-C4 alkoxy acyl and phenyl. The catalyst in step (1) is [ RhCp (MeCN) 3 ](SbF 6 ) 2 、[RhCp*Cl 2 ] 2 、[RhCp*(OAc) 2 ] 2 One or more of them. The solvent in the step (1) is tolueneOne or more of dichloromethane and 1, 2-dichloroethane. The silver salt in the step (1) is AgSbF 6 ，AgOAc，AgBF 4 ，AgNO 3 One or more of them. The reaction concentration of the pyridine triazole compound in the step (1) is 0.1 mol/L. Pyridine triazole compound in step (1): phenyl isocyanate compound: catalyst: the molar ratio of silver salt is 1:3:0.05:0.3.
Detailed Description
The invention is further described below in conjunction with the specific embodiments to facilitate an understanding of the invention. But should not be construed as limiting the scope of the invention, which is defined in the appended claims.
Example 1: synthesis of Compound 1
Sequentially adding 3-phenyl- [1,2,3 into a clean and dry reactor]Triazole- [1,5 ]α]Pyridine (31.4 mg, 0.10 mmol), phenyl isocyanate (35.7 mg,0.30 mmol), [ RhCp ] 3 ](SbF 6 ) 2 (4.1 mg,0.005 mmol), agOAc (5.0 mg,0.03 mmol), dichloromethane (1.0 mL) was stirred at 100℃for 12 hours after the passage of nitrogen. After TLC monitoring the reaction, the solvent is removed under reduced pressure, and the white solid is obtained by separating and purifying by adopting silica gel column chromatography PE/EA, and the melting point is 211.6-212.3 o C, yield 72%. 1 H NMR (400 MHz, Chloroform-d) δ 8.78 (s, 1H), 8.71 (d,J= 7.0 Hz, 1H), 7.96 (d,J= 7.2 Hz, 1H), 7.73 (d,J= 9.0 Hz, 1H), 7.61-7.55 (m, 3H), 7.45 (d,J= 7.8 Hz, 2H), 7.23 (d,J= 6.6 Hz, 3H), 7.05-6.99 (m, 2H). 13 C NMR (100 MHZ, Chloroform-d) Delta 166.98, 137.95, 137.00, 136.83, 132.11, 131.04, 130.76, 130.22, 129.05, 128.88, 127.67, 126.13, 125.37, 124.35, 119.96, 118.11, 115.92. HRMS (ESI) m/z calculated [ C ] 19 H 14 N 4 O，M+H] + :314.3480, found: 314.3478.
example 2: synthesis of Compound 2
Sequentially adding 3-p-tolyl- [1,2,3 into a clean and dry reactor]Triazole [1,5 ]α]Pyridine (20.9 mmol,0.10 mmol), phenyl isocyanate (35.7 mg,0.3 mmol), [ RhCp ] Cl 2 ] 2 （3.0 mg，0.005 mmol），AgSbF 6 (10.3 mg,0.03 mmol), toluene (1.0 mL), was stirred at 100℃for 12 hours after the introduction of nitrogen. After the completion of the reaction by TLC, the solvent was removed under reduced pressure, and the mixture was purified by separation using a silica gel column chromatography PE/EA to give a white solid having a melting point of 187.8 to 188.3 o C, yield 72%. 1 H NMR (400 MHz, Chloroform-d) δ 8.94 (s, 1H), 8.68 (d,J= 7.0 Hz, 1H), 7.76 (s, 1H), 7.69 (d,J= 8.9 Hz, 1H), 7.46 (d,J= 7.6 Hz, 3H), 7.37 (d,J= 7.5 Hz, 1H), 7.26-7.20 (m, 3H), 7.03 (t,J= 7.3 Hz, 1H), 6.97 (t,J= 6.7 Hz, 1H), 2.46 (s, 3H). 13 C NMR (100 MHZ, Chloroform-d) δ 167.18, 139.13, 138.06, 137.07, 136.55, 132.04, 131.49, 130.94, 130.77, 128.83, 125.93, 125.30, 124.70, 124.25, 119.99, 118.16, 115.86, 21.22. HRMS(ESI) m/z: [C 20 H 16 N 4 O，M+H] + Calculated values: 328.3750, found: 328.3755.
example 3: synthesis of Compound 3
Sequentially adding 3-m-methoxyphenyl- [1,2,3 into a clean and dry reactor]Triazole- [1,5 ]α]Pyridine (31.4 mg, 0.10 mmol), phenyl isocyanate (35.7 mg,0.30 mmol), [ RhCp ] 3 ](SbF 6 ) 2 (4.1 mg,0.005 mmol), agOAc (5.0 mg,0.03 mmol), dichloromethane (1.0 mL) was stirred at 100℃for 12 hours after the passage of nitrogen. After the completion of the reaction by TLC, the solvent was removed under reduced pressure, and PE/EA fraction was purified by silica gel column chromatographySeparating and purifying to obtain white solid with melting point of 211.6-212.3 o C, yield 54%. 1 H NMR (400 MHz, Chloroform-d) δ 8.78 (s, 1H), 8.71 (d,J= 7.0 Hz, 1H), 7.95 (d,J= 8.4 Hz, 1H), 7.72 (d,J= 8.9 Hz, 1H), 7.41 (d,J= 7.8 Hz, 2H), 7.22 (t,J= 7.6 Hz, 3H), 7.10 - 7.05 (m, 2H), 7.04 - 6.99 (m, 2H), 3.89 (s, 3H). 13 C NMR (100 MHz, Chloroform-d) Delta 166.63, 161.23, 138.13, 137.01, 132.40, 132.18, 129.36, 129.09, 128.83, 126.24, 125.37, 124.15, 119.83, 118.15, 116.15, 116.00, 114.61, 55.63. HRMS (ESI) m/z calculated [ C ] 19 H 14 N 4 O，M+H] + :344.1273, found: 344.1268.
example 4: synthesis of Compound 4
Sequentially adding 3-phenyl- [1,2,3 into a clean and dry reactor]Triazole [1,5 ]α]Pyridine (31.4 mg, 0.10 mmol), p-toluyl isocyanate (40 mg,0.3 mmol), [ RhCp (OAc) 2 ] 2 （3.3 mg，0.005 mmol），AgBF 4 (5.8 mg,0.03 mmol), 1, 2-dichloroethane (1.0. 1.0 mL), and stirring at 100℃for 12 hours after introducing nitrogen. After the completion of the reaction by TLC, the solvent was removed under reduced pressure, and the mixture was purified by separation using a silica gel column chromatography PE/EA to give a white solid having a melting point of 242.3-245.3 o C, yield 73%. 1 H NMR (400 MHz, Chloroform-d) δ 8.71 (d,J= 7.1 Hz, 1H), 8.59 (s, 1H), 7.95 (d,J= 6.9 Hz, 1H), 7.73 (d,J= 9.0 Hz, 1H), 7.61-7.54 (m, 3H), 7.30 (d,J= 8.3 Hz, 2H), 7.23 (d,J= 8.6 Hz, 1H), 7.05-6.99 (m, 3H), 2.26 (s, 3H). 13 C NMR (100 MHZ, Chloroform-d) δ 166.89, 137.02, 136.88, 135.34, 133.99, 132.09, 131.04, 130.68, 130.12, 129.35, 129.02, 127.67, 126.08, 125.34, 120.02, 118.15, 115.88, 20.87. HRMS(ESI) m/z: [C 20 H 16 N 4 O，M+H] + Calculated values: 328.3750, found: 328.3752.
example 5: synthesis of Compound 5
Sequentially adding 3-phenyl- [1,2,3 into a clean and dry reactor]Triazole- [1,5 ]α]Pyridine (31.4 mg, 0.10 mmol), p-methoxyphenylisocyanate (44.7 mg,0.30 mmol), [ RhCp (MeCN) 3 ](SbF 6 ) 2 （4.1 mg，0.005 mmol），AgNO 3 (5.1 mg,0.03 mmol) and methylene chloride (1.0. 1.0 mL) were stirred at 100℃for 12 hours after the introduction of nitrogen. After TLC monitoring the reaction, the solvent is removed under reduced pressure, and the white solid is obtained by separating and purifying by adopting silica gel column chromatography PE/EA, and the melting point is 211.6-212.3 o C, yield 75%. 1 H NMR (400 MHz, Chloroform-d) δ 8.65 (d,J= 7.1 Hz, 1H), 8.46 (s, 1H), 7.89 (d,J= 7.0 Hz, 1H), 7.67 (d,J= 9.0 Hz, 1H), 7.56 - 7.46 (m, 3H), 7.24 (s, 1H), 7.19 (s, 2H), 6.94 (t,J= 6.8 Hz, 1H), 6.71 (d,J= 8.9 Hz, 2H), 3.68 (s, 3H). 13 C NMR (100 MHz, Chloroform-d) Delta 166.78, 156.42, 137.05, 136.86, 132.09, 131.04, 131.00, 130.62, 130.10, 129.00, 127.62, 126.05, 125.32, 121.69, 118.16, 115.87, 114.02, 55.42. HRMS (ESI) m/z calculated [ C ] 20 H 16 N 4 O 2 ，M+H] + :344.1273, found: 344.1271.
example 6: synthesis of Compound 6
Sequentially adding 3-phenyl- [1,2,3 into a clean and dry reactor]Triazole- [1,5 ]α]Pyridine (31.4 mg, 0.10 mmol), m-chlorobenzeneisocyanate (46.1 mg,0.30 mmol), [ RhCp (MeCN) 3 ](SbF 6 ) 2 (4.1 mg,0.005 mmol), agOAc (5.0 mg,0.03 mmol), dichloromethane (1.0 mL) was stirred at 100℃for 12 hours after the passage of nitrogen. After completion of the reaction by TLC, the solvent was removed under reduced pressureSeparating and purifying by silica gel column chromatography PE/EA to obtain white solid with melting point of 211.6-212.3 o C, yield 71%. 1 H NMR (400 MHz, Chloroform-d) δ 9.61 (s, 1H), 8.73 (d,J= 7.0 Hz, 1H), 7.83 (d,J= 7.5 Hz, 1H), 7.73 - 7.70 (m, 2H), 7.54 - 7.40 (m, 4H), 7.32 (d,J= 7.9 Hz, 1H), 7.12 (t,J= 8.0 Hz, 1H), 7.03 (t,J= 6.8 Hz, 1H), 6.98 (d,J= 7.9 Hz, 1H). 13 C NMR (100 MHz, Chloroform-d) δ167.11, 139.37, 136.92, 136.54, 134.44, 132.01, 130.75, 130.73, 130.20, 129.73, 128.82, 127.67, 126.22, 125.47, 124.21, 119.96, 118.07, 117.89, 116.03. HRMS (ESI) m/z calculated [ C 19 H 13 ClN 4 O，M+H] + :348.0778, found: 348.0772.
example 7: synthesis of Compound 7
Sequentially adding 3-phenyl- [1,2,3 into a clean and dry reactor]Triazole- [1,5 ]α]Pyridine (31.4 mg, 0.10 mmol), methyl 4-isocyanatobenzoate (53.1 mg,0.30 mmol), [ RhCp (MeCN) 3 ](SbF 6 ) 2 (4.1 mg,0.005 mmol), agOAc (5.0 mg,0.03 mmol), dichloromethane (1.0 mL) was stirred at 100℃for 12 hours after the passage of nitrogen. After TLC monitoring the reaction, the solvent is removed under reduced pressure, and the white solid is obtained by separating and purifying by adopting silica gel column chromatography PE/EA, and the melting point is 211.6-212.3 o C, yield 66%. 1 H NMR (400 MHz, Chloroform-d) δ 9.55 (s, 1H), 8.73 (d,J= 7.0 Hz, 1H), 7.93 (dd,J= 14.4, 8.0 Hz, 3H), 7.71 (d,J= 8.9 Hz, 1H), 7.63 - 7.52 (m, 5H), 7.29 (s, 1H), 7.03 (t,J= 6.7 Hz, 1H), 3.87 (s, 3H). 13 C NMR (100 MHz, Chloroform-d) Delta 167.10, 166.62, 142.34, 136.90, 136.46, 132.11, 130.94, 130.91, 130.68, 130.48, 129.00, 127.62, 126.29, 125.51, 125.47, 118.99, 118.02, 116.08, 51.96. HRMS (ESI) m/z calculated [ C 21 H 16 N 4 O 3 ，M+H] + :372.1222, found: 372.1217.
embodiment case 8: synthesis of Compound 8
Sequentially adding 3-phenyl- [1,2,3 into a clean and dry reactor]Triazole- [1,5 ]α]Pyridine (31.4 mg, 0.10 mmol), 2-biphenylisocyanate (58.6 mg,0.30 mmol), [ RhCp (MeCN) 3 ](SbF 6 ) 2 (4.1 mg,0.005 mmol), agOAc (5.0 mg,0.03 mmol), dichloromethane (1.0 mL) was stirred at 100℃for 12 hours after the passage of nitrogen. After TLC monitoring the reaction, the solvent is removed under reduced pressure, and the white solid is obtained by separating and purifying by adopting silica gel column chromatography PE/EA, and the melting point is 211.6-212.3 o C, yield thereof was found to be 49%. 1 H NMR (600 MHz, Chloroform-d) δ 8.70 (d,J= 6.4 Hz, 1H), 8.28 (d,J= 7.4 Hz, 1H), 7.77 (d,J= 8.9 Hz, 1H), 7.70 - 7.64 (m, 3H), 7.53 (t,J= 7.5 Hz, 1H), 7.45 (t,J= 7.4 Hz, 1H), 7.34 - 7.26 (m, 4H), 7.25 - 7.21 (m, 1H), 7.13 (s, 2H), 7.02 - 6.96 (m, 3H). 13 C NMR (100 MHz, Chloroform-d) Delta 167.63, 137.69, 136.35, 134.62, 132.86, 131.50, 130.68, 130.61, 130.07, 128.91, 128.86, 128.73, 128.55, 128.27, 128.25, 127.82, 125.86, 125.40, 124.54, 121.61, 118.19, 115.47. HRMS (ESI) m/z calculated [ C ] 19 H 14 N 4 O，M+H] + :390.1481, found: 390.1479.
Claims (7)
1. a method for synthesizing amide compounds by rhodium catalyzed pyridine triazole and phenyl isocyanate is characterized in that pyridine triazole compounds and phenyl isocyanate compounds are used as raw materials, and C-H activation is carried out to synthesize amide compounds in the presence of a transition metal rhodium catalyst and silver salt, wherein the chemical reaction formula is as follows:
，
wherein:
R 1 is one or more of hydrogen, C1-C5 alkyl and C1-C5 alkoxy; r is R 2 Is one or more of hydrogen, C1-C5 alkyl, C1-C5 alkoxy, halogen, C1-C4 alkoxy acyl and phenyl;
pyridine triazole means [1,2,3 ] having substituent at 3-position]Triazole- [1,5 ]α]Pyridine.
2. The method for synthesizing amide compounds by rhodium-catalyzed pyridine triazole and phenyl isocyanate as claimed in claim 1, which is characterized by comprising the following preparation steps:
adding pyridine triazole compounds, phenyl isocyanate compounds, transition metal rhodium catalysts, silver salts and solvents into a clean and dry pressure-resistant bottle, sealing, introducing nitrogen, heating and stirring for reaction; after the reaction is finished, the solvent is removed under reduced pressure, and the product is obtained by adopting silica gel column chromatography separation and purification.
3. The method for synthesizing amide compounds from pyridine triazole and phenyl isocyanate catalyzed by rhodium according to claim 2, wherein the solvent is one or more of toluene, methylene dichloride and 1, 2-dichloroethane.
4. The method for synthesizing amide compounds by rhodium catalyzed pyridine triazole and phenyl isocyanate according to claim 2, wherein the catalyst is [ RhCp (MeCN) 3 ](SbF 6 ) 2 、[RhCp*Cl 2 ] 2 、[RhCp*(OAc) 2 ] 2 One or more of them.
5. The method for synthesizing amide compounds from pyridine triazole and phenyl isocyanate catalyzed by rhodium according to claim 2, wherein the silver salt is AgSbF 6 ，AgOAc，AgBF 4 ，AgNO 3 One or more of them.
6. The method for synthesizing amide compounds from pyridine triazole and phenyl isocyanate under the catalysis of rhodium according to claim 2, wherein the reaction concentration of the pyridine triazole compound is 0.1 mmol/L, and the pyridine triazole compound is: phenyl isocyanate compound: catalyst: the molar ratio of silver salt is 1:3:0.05:0.3.
7. the method for synthesizing amide compounds by rhodium catalyzed pyridine triazole and phenyl isocyanate according to claim 2, wherein the reaction temperature is 100 ℃ and the reaction time is 12 hours.
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