A method for synthesizing selenide aryl or selenide olefin amine compounds catalyzed by palladium

Abstract

The present invention belongs to the field of drug synthesis, and specifically relates to a method for synthesizing selenized aryl or selenized alkenyl amine compounds catalyzed by palladium. At present, the activation of carbon-hydrogen bonds remains at γ-C(sp3)-H sulfidation or selenidation, and the remote δ-C(sp2)-H position selenidation of the directing group has not been achieved. The present invention provides a remote δ-C(sp 2 The invention discloses a method for selenization at the δ-C(sp2)-H position, specifically, under an inert gas, compound I, compound II, a palladium catalyst, an oxidant and a solvent are mixed and reacted directly to obtain compound III, thereby realizing the progressive selenization at δ-C(sp2)-H of the directing group (-NHPA). The method has mild reaction conditions, simple operation and high reaction yield, which can reach up to 98%. The reaction substrate has wide adaptability, and aromatic, heteroaryl and alkenyl compounds can all achieve selenization of C(sp2)-H bonds.

Description

Technical Field

[0001] The invention belongs to the field of drug synthesis, and in particular relates to a method for synthesizing selenized aryl or selenized alkenyl amine compounds by using palladium as catalyst. Background Art

[0002] C(sp 2 )-Se bonds are widely present in various functional materials, fluorescent probes, candidate drugs and bioactive molecules. For example, aryl selenides are widely present in many drugs for treating cancer, SARS-CoV2 and pain diseases. Therefore, in the past few decades, the construction of C-Se bonds has been the focus of chemists. The construction of traditional C-Se bonds largely relies on the direct cross-coupling reaction of metal thiolates with pre-functionalized aryl halides or aryl boronic acids. The long reaction route and harsh reaction conditions lead to poor functional group tolerance, and the diversity of products is greatly limited. Therefore, it is very necessary to explore a new synthetic route with mild reaction conditions, good substrate tolerance and shorter reaction steps.

[0003] In recent years, transition metal-catalyzed C-H bond functionalization to construct C-Se has atom and step economy and has become an important strategy for the synthesis or structural modification of bioactive molecules. In this context, transition metal-catalyzed direct ortho-directing group-assisted selective C-H selenylation (sulfurization) reactions have been gradually developed. As early as 2012, Daugulis's group used bidentate directing groups to achieve copper-promoted sulfurization of inert γ-C-H bonds of benzylamine derivatives to obtain disulfide products. Subsequently, Nishihara and Li successfully achieved direct C-H sulfurization of aryl pyridines using palladium and rhodium catalysts, respectively. In 2014, Nishihara's group used a pyridine amide bidentate system to selectively C-H sulfurize naphthalene at the 1 position under palladium catalysis. Inspired by this work, Xie's group recently further expanded the substrate range to benzyl γ-C (sp 3 )-H sulfidation reaction.

[0004] Although great progress has been made in transition metal-catalyzed carbon-hydrogen selenization (sulfurization) reactions in recent years, these reactions are mostly limited to the functionalization of the CH bond ortho to the directing group, and the more challenging remote δ-position CH selenization of arylethylamines and alkenylamines has not yet been reported. Therefore, it is necessary to develop a transition metal palladium-catalyzed remote δ-C (sp 2 The )-H reaction method for constructing seleninated arylethylamines or alkenylethylamines is of great significance and lays the foundation for the development of drugs. Summary of the invention

[0005] In view of the above problems, the object of the present invention is to provide a method for synthesizing selenized aryl or selenized alkenyl amine compounds using palladium catalysis.

[0006] The method of the present invention solves the problem of long-range δ-position CH selenization of the directing group, specifically, the δ-C (sp 2 The method of the present invention has mild conditions, simple operation, high reaction yield and wide adaptability of reaction substrates.

[0007] The reaction mechanism of synthesizing selenide arylethylamine in the present invention is:

[0008] First, palladium acetate coordinates with the bidentate directing group of substrate 1a, and generates a six-membered ring palladium intermediate A through reversible CH activation. Intermediate A undergoes oxidative addition with substrate 2a to generate Pd(IV) intermediate B, and then undergoes reduction elimination to generate target product 3aa and Pd(II) intermediate C. Intermediate C can coordinate with another molecular substrate 1a to generate Pd(II) intermediate D, and then undergoes reduction elimination to generate target product 3aa and Pd(0) species. Pd(0) species is finally oxidized by silver acetate to generate palladium acetate and participate in the next round of catalytic cycle. The present invention mainly involves the catalytic cycle of Pd(II)→Pd(IV)→Pd(II)→Pd(0)→Pd(II).

[0009]

[0010] The specific plan is as follows:

[0011] A method for preparing compound III, comprising reacting compound I, compound II with a palladium catalyst and an oxidant in a solvent to obtain compound III; wherein the structural formulas of compound I, compound II and compound III are as follows:

[0012]

[0013] Wherein X is independently selected from

[0014]

[0015] R 1 Independently selected from hydrogen, ester group, alkyl group;

[0016] R 2 Independently selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; the substituent is halogen, alkyl, alkoxy;

[0017] R 3 , R 4 are independently selected from hydrogen, halogen, hydroxyl, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; the substituent is halogen, alkyl, alkoxy;

[0018] In the technical solution of the present invention, R 1 Independently selected from hydrogen, ester group, alkyl group;

[0019] R 2 Independently selected from substituted or unsubstituted aryl; the substituent is halogen, alkyl, alkoxy;

[0020] R 3 , R 4 are independently selected from hydrogen, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; the substituent is halogen, alkyl, alkoxy;

[0021] Furthermore, R 1 independently selected from hydrogen, -COOC 2 H 5 ,methyl;

[0022] R 2 Independently selected from substituted or unsubstituted aryl; the substituent is halogen, alkyl, alkoxy;

[0023] R 3 , R 4 They are independently selected from hydrogen, halogen, nitro, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C1-C10 alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; the substituent is halogen, alkyl, alkoxy.

[0024] In the technical solution of the present invention, the R 2 Independently selected from substituted or unsubstituted aryl; the substituent is F, Cl, Br, C1-C10 alkyl, C1-C10 alkoxy;

[0025] R 3 , R 4 They are independently selected from hydrogen, halogen, nitro, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted aryl; the substituents are F, Cl, Br, C1-C10 alkyl, C1-C10 alkoxy.

[0026] Furthermore, R 2 Independently selected from substituted or unsubstituted aryl; the substituent is F, Cl, Br, C1-C4 alkyl, C1-C4 alkoxy;

[0027] R 3 , R 4They are independently selected from hydrogen, F, Cl, Br, nitro, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted aryl; the substituent is F, Cl, Br, C1-C6 alkyl, C1-C6 alkoxy.

[0028] Furthermore, R 2 Independently selected from substituted or unsubstituted aryl; the substituent is F, Cl, Br, methyl, methoxy;

[0029] R 3 , R 4 Each is independently selected from hydrogen, F, Cl, Br, nitro, methyl, methoxy, phenyl and 4-fluorophenyl.

[0030] In the specific technical scheme of the present invention, compound III is selected from one of the following structural formulas:

[0031]

[0032]

[0033] In the technical solution of the present invention, the palladium catalyst is Pd(OAc) 2 .

[0034] Furthermore, the oxidant is AgOAc, Ag 2 O、AgNO 3 、Ag 2 CO 3 、AgOPiv、PhI(OAc) 2 , K 2 S 2 O 8 One or more of;

[0035] Furthermore, the oxidant is AgOAc, Ag 2 CO 3 , AgOPiv or one or more thereof.

[0036] Further, the solvent is one or more of toluene, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethyl sulfoxide, acetonitrile, 1,2-dichloroethane, trifluoroethanol, and hexafluoroisopropanol;

[0037] Furthermore, the solvent is one or more of toluene, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethyl sulfoxide, acetonitrile, and 1,2-dichloroethane.

[0038] From the screening results of Example 1, it can be seen that when the solvent is toluene and the oxidant is silver acetate, the reaction has a higher yield. Therefore, in the technical aspect of the present invention, toluene is preferably used as the solvent and silver acetate is used as the oxidant.

[0039] In the technical solution of the present invention, the molar ratio of compound I to compound II is 1:1-10; the added palladium catalyst is 1-10 mol%; and the molar ratio of compound I to oxidant is 1:1-10.

[0040] Furthermore, the molar ratio of compound I to compound II is 1:2-5; the added palladium catalyst is 3-7 mol%; and the molar ratio of compound I to oxidant is 1:2-5.

[0041] Furthermore, the molar ratio of compound I to compound II is 1:1.5; the added palladium catalyst is 5 mol%; and the molar ratio of compound I to the oxidant is 1:1.5.

[0042] In the technical solution of the present invention, compound III is obtained by directly reacting compound I, compound II, a palladium catalyst, an oxidant and a solvent under an inert gas, and the reaction temperature is 100-140°C.

[0043] In the technical solution of the present invention, the reaction temperature is 120°C.

[0044] Symbols in this invention Indicates that the carbon-carbon bond is broken at the position marked by the symbol.

[0045] In the present invention, AgOAc represents silver acetate;

[0046] In the present invention, Ag 2 O represents silver oxide;

[0047] In the present invention, AgNO 3 represents silver nitrate;

[0048] In the present invention, Ag 2 CO 3 represents silver carbonate;

[0049] In the present invention, AgOPiv represents silver pivalate;

[0050] In the present invention, PhI(OAc) 2 represents iodobenzene diacetate;

[0051] In the present invention, K 2 S 2 O 8 It stands for potassium persulfate.

[0052] In the present invention, the group represented by -NHPA is

[0053] The beneficial effects of the present invention are:

[0054] 1. For the first time, the δ-C(sp2)-H progressive selenization of the directing group (-NHPA) was achieved.

[0055] 2. The reaction conditions are mild, the operation is simple, and the reaction yield is high, up to 98%.

[0056] 3. The reaction substrates have wide adaptability. Aromatic amines, heteroaryl amines, and alkenyl amine compounds can all achieve selenization of δ-C(sp2)-H bonds. DETAILED DESCRIPTION

[0057] The technical solution of the present invention is further defined below in conjunction with specific implementation methods, but the scope of protection required is not limited to the description.

[0058] The drugs and reagents used in the present invention can be purchased through commercial channels.

[0059] Example 1: Screening of solvents and oxidants

[0060]

[0061] The present invention screened the solvent and oxidant used in the reaction, and the solvent and oxidant used are shown in Table 1.

[0062] Table 1 Screening of solvents and oxidants

[0063]

[0064] The specific experimental operation of No. 1 to No. 16 is as follows: 0.20mmol of arylethylamine substrate and 1.5 equivalents of diaryl diselenide are mixed under anhydrous and oxygen-free operation, 5mol% of catalyst and 2.0 equivalents of oxidant are added to the reaction tube, dry solvent is added under nitrogen protection, and the mixture is reacted at 120℃ for 12h to obtain a mixed liquid. After the reaction is completed, water and ethyl acetate are added for extraction three times, the organic layers are combined, and anhydrous Na 2 SO 4 The organic layer was dried, filtered, concentrated, and separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate=30 / 1-5 / 1) to obtain selenized arylethylamine compounds.

[0065] The specific experimental operation of No. 17 is as follows: 0.20mmol of arylethylamine substrate and 1.5 equivalents of diaryl diselenide are mixed under anhydrous and oxygen-free operation, 2.5mol% of catalyst and 2.0 equivalents of oxidant are added to the reaction tube, dry solvent is added under nitrogen protection, and the mixture is reacted at 120°C for 12h to obtain a mixed liquid. After the reaction is completed, water and ethyl acetate are added for extraction three times, the organic layers are combined, and anhydrous Na 2 SO4 The organic layer was dried, filtered, concentrated, and separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate=30 / 1-5 / 1) to obtain selenized arylethylamine compounds.

[0066] The specific experimental operation of No. 18 is as follows: 0.20mmol of arylethylamine substrate and 1.5 equivalents of diaryl diselenide are mixed under anhydrous and oxygen-free operation, 5mol% of catalyst and 2.0 equivalents of oxidant are added to the reaction tube, dry solvent is added under argon protection, and the mixture is reacted at 100°C for 12h to obtain a mixed liquid. After the reaction is completed, water and ethyl acetate are added for extraction three times, the organic layers are combined, and anhydrous Na 2 SO 4 The organic layer was dried, filtered, concentrated, and separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate=30 / 1-5 / 1) to obtain the selenized aryl group.

[0067] The specific experimental operation of No. 19 is as follows: 0.20mmol of arylethylamine substrate and 1.5 equivalents of diaryl diselenide are mixed under anhydrous and oxygen-free operation, 5mol% of catalyst and 1.5 equivalents of oxidant are added to the reaction tube, dry solvent is added under argon protection, and the mixture is reacted at 120°C for 12h to obtain a mixed liquid. After the reaction is completed, water and ethyl acetate are added for extraction three times, the organic layers are combined, and anhydrous Na 2 SO 4 The organic layer was dried, filtered, concentrated, and separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate=30 / 1-5 / 1) to obtain selenized arylethylamine compounds.

[0068] The specific experimental operation of No. 20 is as follows: 0.20 mmol of arylethylamine substrate and 1.5 equivalents of diaryl diselenide are mixed under anhydrous and oxygen-free operation, 5 mol% of catalyst is added to the reaction tube, dry solvent is added under nitrogen protection, and the mixture is reacted at 120° C. for 12 hours to obtain a mixed liquid. Trace products are detected after the reaction.

[0069] The specific experimental operation of No. 21 is as follows: 0.20 mmol of arylethylamine substrate and 1.5 equivalents of diaryl diselenide are mixed under anhydrous and oxygen-free operation, 1.5 equivalents of oxidant are added to the reaction tube, dry solvent is added under nitrogen protection, and the mixture is reacted at 120° C. for 12 hours to obtain a mixed liquid. No product is detected after the reaction is completed.

[0070] Example 2 Expansion of aryl or heteroaryl reaction substrates

[0071] Under anhydrous and oxygen-free conditions, 0.20 mmol of an aryl (or heteroaryl) ethylamine substrate and 1.5 equiv of a diaryl diselenide were mixed, and 5 mol% of a catalyst Pd(OAc) was added. 2and 1.5 equiv of oxidant AgOAc were added to the reaction tube, and dry toluene (2 mL) was added under argon protection, and the mixture was reacted at 120 °C for 12 h to obtain a mixed liquid. After the reaction was completed, water and ethyl acetate were added for extraction three times, and the organic layers were combined and anhydrous Na 2 SO 4 The organic layer was dried, filtered, concentrated, and separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30 / 1-5 / 1) to obtain selenized aryl (or heteroaryl) ethylamine compounds. The reaction products and yields are as follows:

[0072]

[0073]

[0074] In the present invention, in the reaction of synthesizing product 3ka, a disubstituted selenide product 3ka is also found. In a specific embodiment of the present invention, when the meta position of the substrate aromatic group contains a substituent, due to the steric hindrance effect, the selenide reaction selectively occurs on the side with less steric hindrance, such as products 3ga~3ja, 3la~3na, 3pa, 3sa.

[0075] Example 3 Expansion of olefinic reaction substrates

[0076] Under anhydrous and oxygen-free conditions, 0.20 mmol of alkenylethylamine substrate and 1.5 equivalents of diaryl diselenide were mixed, and 5 mol% of catalyst Pd(OAc) was added. 2 and 1.5 equiv of oxidant AgOAc were added to the reaction tube, and dry toluene (2 mL) was added under argon protection, and the mixture was reacted at 120 °C for 12 h to obtain a mixed liquid. After the reaction was completed, water and ethyl acetate were added for extraction three times, and the organic layers were combined and anhydrous Na 2 SO 4 The organic layer was dried, filtered, concentrated, and separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30 / 1-5 / 1) to obtain selenide-containing alkenylethylamine compounds. The reaction products and yields are as follows:

[0077]

[0078] Through comparative experiments, it was found that when no palladium catalyst was added to the synthesis reaction of product 3ya and product 3za, product 3ya and product 3za could not be synthesized.

[0079] Example 4 Structural Characterization of Each Product

[0080]

[0081] N-(2-methyl-6-(phenylselanyl)phenethyl)picolinamide(3aa). 1H NMR(600MHz,CDCl 3 )δ=8.55(dd,J=4.6,1.5Hz,1H),8.30–8.28(m,1H),8.21(d,J=7.7Hz,1H),7.87–7.84(m,1H),7.43(dd,J=7.6,4.8Hz,1H),7.41–7.37(m,2H),7.27–7.25(m,3H),7.23(d,J=7.9Hz,1H),7.13(d,J=7.5Hz,1H),7.03–7.01(m,1H),3.67–3.61(m,2H),3.23–3.19(m,2H),2.49(s,3H).HR-MS(ESI)m / z calcd for:C 21 H 21 N 2 O 80 Se + [M+H] + 397.0814,found397.0814.

[0082]

[0083] N-(2-methoxy-6-(phenylselanyl)phenethyl)picolinamide(3ba). 1 H NMR(600MHz,CDCl 3 )δ=8.52(d,J=4.7Hz,1H),8.39(s,1H),8.18(d,J=7.8Hz,1H),7.83–7.80(m,1H),7.42–7.38(m,3H),7.26–7.23(m,3H),7.08–7.05(m,1H),6.92(d,J=7.8Hz,1H),6.79(d,J=8.1Hz,1H),3.86(s,3H),3.70–3.67(m,2H),3.23(t,J=6.9Hz,2H).HR-MS(ESI)m / z calcd for:C 21 H 21 N 2 O 2 80 Se + [M+H] + 413.0763,found 413.0763.

[0084]

[0085] N-(2-fluoro-6-(phenylselanyl)phenethyl)picolinamide(3ca). 1 H NMR(600MHz,CDCl 3 )δ=8.53(d,J=4.8Hz,1H),8.23–8.19(m,2H),7.85–7.82(m,1H),7.43–7.40(m,3H),7.28(d,J=5.4Hz,3H),7.11–7.04(m,2H),6.99–6.93(m,1H),3.73–3.70(m,2H),3.21(t,J=7.3Hz,2H).HR-MS(ESI)m / z calcd for:C 20 H 17 FN 2 NaO 80 Se + [M+Na] + 423.0382,found 423.0383.

[0086]

[0087] N-(2-chloro-6-(phenylselanyl)phenethyl)picolinamide(3da). 1 H NMR(600MHz,CDCl 3 )δ=8.54(d,J=4.6Hz,1H),8.27(s,1H),8.21(d,J=7.6Hz,1H),7.86–7.83(m,1H),7.44–7.41(m,3H),7.29(d,J=5.2Hz,3H),7.26(s,1H),7.15(d,J=7.8Hz,1H),7.01–6.99(m,1H),3.78–3.74(m,2H),3.36(t,J=7.6Hz,2H).HR-MS(ESI)m / z calcd for:C 20 H 18 ClN 2 O 80 Se + [M+H] + 417.0267,found 417.0266.

[0088]

[0089] N-(2-bromo-6-(phenylselanyl)phenethyl)picolinamide(3ea). 1 H NMR(600MHz,CDCl 3 )δ=8.55(d,J=4.8Hz,1H),8.33–8.19(m,2H),7.86–7.83(m,1H),7.50–7.39(m,4H),7.29(d,J=6.6Hz,3H),7.18(d,J=7.8Hz,1H),6.92–6.90(m,1H),3.78–3.75(m,2H),3.39(t,J=7.6Hz,2H).HR-MS(ESI)m / z calcd for:C 20 H 18 BrN 2 O 80 Se + [M+H] + 460.9762,found 460.9762.

[0090]

[0091] N-(2-(phenylselanyl)-6-(trifluoromethyl)phenethyl)picolinamide(3fa). 1 H NMR(600MHz,CDCl 3 )δ=8.59–8.53(m,1H),8.34–8.20(m,2H),7.87–7.84(m,1H),7.56(d,J=7.9Hz,1H),7.50(d,J=7.0Hz,2H),7.44–7.43(m,1H),7.39(d,J=8.1Hz,1H),7.33(d,J=6.6Hz,3H),7.16–7.13(m,1H),3.79–3.76(m,2H),3.36(t,J=8.2Hz,2H).HR-MS(ESI)m / z calcd for:C 21 H 17 F 3 N 2 NaO 80 Se + [M+Na] + 473.0350,found 473.0351.

[0092]

[0093] N-(5-fluoro-2-(phenylselanyl)phenethyl)picolinamide(3ga). 1 H NMR(600MHz,CDCl 3 )δ=8.52(ddd,J=4.8,1.7,0.9Hz,1H),8.23–8.12(m,2H),7.86–7.83(m,1H),7.48(dd,J=8.6,5.9Hz,1H),7.42(ddd,J=7.6,4.8,1.2Hz,1H),7.33–7.29(m,2H),7.25–7.19(m,3H),7.09–7.07(m,1H),6.89–6.86(m,1H),3.71–3.67(m,2H),3.13(t,J=7.3Hz,2H).HR-MS(ESI)m / z calcd for:C 20 H 17 FN 2 O 80 Se + [M+H] + 401.0563,found 401.0566.

[0094]

[0095] N-(5-chloro-2-(phenylselanyl)phenethyl)picolinamide(3ha). 1 H NMR(600MHz,CDCl 3 )δ=8.53(ddd,J=4.8,1.7,0.9Hz,1H),8.23–8.15(m,2H),7.86–7.83(m,1H),7.42(ddd,J=7.6,4.7,1.2Hz,1H),7.39–7.35(m,2H),7.32(d,J=2.4Hz,1H),7.31(d,J=8.3Hz,1H),7.27–7.25(m,3H),7.09(dd,J=8.3,2.4Hz,1H),3.72–3.67(m,2H),3.12–3.08(m,2H).HR-MS(ESI)m / z calcd for:C 20 H 17 ClN 2 NaO 80 Se + [M+Na] + 439.0087,found439.0088.

[0096]

[0097] N-(5-bromo-2-(phenylselanyl)phenethyl)picolinamide(3ia). 1 H NMR(600MHz,CDCl 3 )δ=8.57–8.51(m,1H),8.21–8.18(m,2H),7.86–7.84(m,1H),7.46(s,1H),7.42(d,J=6.2Hz,1H),7.40–7.36(m,2H),7.28–7.26(m,3H),7.23–7.21(m,2H),3.71–3.68(m,2H),3.10–3.08(m,2H). 13 C NMR(150MHz,CDCl 3 )δ=164.5,149.9,148.1,142.8,137.6,137.5,136.1,133.1,132.9,131.0,130.9,130.7,129.7,127.7,126.3,122.4,40.0,36.0.HR-MS(ESI)m / z calcd for:C 20 H 17 BrN 2 NaO 80 Se + [M+Na] + 482.9582,found 482.9581.

[0098]

[0099] N-(2-(phenylselanyl)-5-(trifluoromethyl)phenethyl)picolinamide(3ja). 1 H NMR(600MHz,CDCl 3 )δ=8.53(d,J=4.8Hz,1H),8.21(d,J=8.0Hz,2H),7.87–7.85(m,1H),7.52(d,J=7.1Hz,2H),7.48(s,1H),7.44–7.42(m 1H),7.39–7.32(m,3H),7.28(d,J=8.4Hz,1H),7.24(d,J=8.3Hz,1H),3.79–3.76(m,2H),3.16(t,J=7.3Hz,2H).HR-MS(ESI)m / z calcd for:C21 H 17 F 3 N 2 NaO 80 Se + [M+Na] + 473.0350,found 473.0351.

[0100]

[0101] N-(4-nitro-2-(phenylselanyl)phenethyl)picolinamide(3ka). 1 H NMR(600MHz,CDCl 3 )δ=8.53(ddd,J=4.8,1.7,0.9Hz,1H),8.25–8.16(m,2H),8.04–7.98(m,2H),7.87–7.85(m,1H),7.54–7.50(m,2H),7.46–7.41(m,2H),7.41–7.37(m,2H),7.37–7.34(m,1H),3.82–3.76(m,2H),3.21(t,J=7.1Hz,2H).HR-MS(ESI)m / z calcd for:C 20 H 17 N 3 NaO 80 Se + [M+Na] + 450.0327,found 450.0329.

[0102]

[0103] N-(4-nitro-2,6-bis(phenylselanyl)phenethyl)picolinamide(3ka”). 1 H NMR(600MHz,CDCl 3)δ=8.56(dd,J=4.8,1.4Hz,1H),8.34–8.32(m,1H),8.22(d,J=7.6Hz,1H),7.87–7.84(m,1H),7.74(s,2H),7.55(s,2H),7.53(d,J=1.9Hz,2H),7.44(dd,J=7.5,4.8Hz,1H),7.42–7.40(m,1H),7.40(s,1H),7.38(d,J=7.6Hz,3H),7.36(s,1H),3.87–3.81(m,2H),3.47–3.42(m,2H).HR-MS(ESI)m / z calcd for:C 26 H 21 N 3 NaO 3 80 Se 2 + [M+Na] + 605.9806,found 605.9810.

[0104]

[0105] N-(4,5-dichloro-2-(phenylselanyl)phenethyl)picolinamide(3la). 1 H NMR(600MHz,CDCl 3 )δ=8.53(ddd,J=4.8,1.7,0.9Hz,1H),8.21–8.18(m,2H),7.86–7.84(m,1H),7.43(ddd,J=7.7,3.9,2.1Hz,3H),7.38(s,1H),7.35(s,1H),7.32–7.29(m,3H),3.71–3.68(m,2H),3.07–3.05(m,2H).HR-MS(ESI)m / z calcd for:C 20 H 16 Cl 2 N 2 NaO 80 Se + [M+Na] + 472.9697,found 472.9698.

[0106]

[0107] N-(4,5-dimethyl-2-(phenylselanyl)phenethyl)picolinamide(3ma). 1 H NMR(600MHz,CDCl 3 )δ=8.53–8.49(m,1H),8.19(d,J=7.8Hz,1H),8.16(d,J=6.1Hz,1H),7.84–7.81(m,1H),7.40(dd,J=7.4,5.1Hz,1H),7.33(s,1H),7.28(d,J=7.0Hz,2H),7.22–7.20(m,2H),7.17(d,J=6.8Hz,1H),7.15(s,1H),3.66–3.63(m,2H),3.07(t,J=7.4Hz,2H),2.23(s,3H),2.18(s,3H).HR-MS(ESI)m / z calcdfor:C 22 H 22 N 2 NaO 80 Se + [M+Na] + 433.0790,found 433.0794.

[0108]

[0109] N-(4,5-dimethoxy-2-(phenylselanyl)phenethyl)picolinamide(3na). 1 H NMR(600MHz,CDCl 3 )δ=8.51(dd,J=4.8,1.5Hz,1H),8.22–8.11(m,2H),7.86–7.82(m,1H),7.41(dd,J=7.6,4.8Hz,1H),7.25–7.22(m,2H),7.22–7.19(m,2H),7.19–7.14(m,1H),7.11(s,1H),6.89(s,1H),3.84(s,3H),3.80(s,3H),3.66–3.33(m,2H),3.09(t,J=7.2Hz,2H).HR-MS(ESI)m / z calcd for:C 22 H 22 N 2 NaO 3 80 Se + [M+Na] +465.0688,found 465.0688.

[0110]

[0111] N-(2,4-dichloro-6-(phenylselanyl)phenethyl)picolinamide(3oa). 1 H NMR(600MHz,CDCl 3 )δ=8.54(ddd,J=4.7,1.8,0.9Hz,1H),8.28–8.26(m,1H),8.22–8.20(m,1H),7.86–7.83(m,1H),7.50–7.46(m,2H),7.42(ddd,J=7.6,4.8,1.2Hz,1H),7.38–7.35(m,1H),7.35–7.30(m,2H),7.26(d,J=2.2Hz,1H),7.00(d,J=2.1Hz,1H),3.77–3.72(m,2H),3.31–3.29(m,2H).HR-MS(ESI)m / z calcd for:C 20 H 16 Cl 2 N 2 NaO 80 Se + [M+Na] + 472.9697,found 472.9697.

[0112]

[0113] N-(2-(3-(phenylselanyl)naphthalen-2-yl)ethyl)picolinamide(3pa). 1 H NMR(600MHz,CDCl 3 )δ=8.50(d,J=4.9Hz,1H),8.21(d,J=8.3Hz,2H),7.96(s,1H),7.85–7.83(m,1H),7.79(s,1H),7.76(d,J=8.1Hz,1H),7.67(d,J=8.1Hz,1H),7.47–7.44(m,2H),7.43–7.37(m,4H),7.26–7.25(m,2H),3.82–3.78(m,2H),3.28–3.23(m,2H).HR-MS(ESI)m / zcalcd for:C 24 H 20 N2 NaO 80 Se + [M+Na] + 455.0633,found 455.0635.

[0114]

[0115] Ethyl 3-(2-chloro-6-(phenylselanyl)phenyl)-2-(picolinamido)propanoate(3qa). 1 H NMR(600MHz,CDCl 3 )δ=8.79(d,J=8.9Hz,1H),8.56(dd,J=4.8,1.6Hz,1H),8.08(d,J=7.8Hz,1H),7.80–7.77(m,1H),7.41(dd,J=7.6,1.8Hz,2H),7.40–7.37(m,1H),7.28–7.25(m,3H),7.24(d,J=3.1Hz,1H),7.15(d,J=7.7Hz,1H),6.99–6.97(m,1H),5.37–5.33(m,1H),4.26–4.18(m,2H),3.65–3.55(m,2H),1.23(t,J=7.2Hz,3H).HR-MS(ESI)m / zcalcd for:C 23 H 21 ClN 2 NaO 3 80 Se + [M+Na] + 511.0298,found 511.0299.

[0116]

[0117] Ethyl 3-(2-bromo-6-(phenylselanyl)phenyl)-2-(picolinamido)propanoate(3ra). 1 H NMR(600MHz,CDCl 3)δ=8.82(d,J=9.0Hz,1H),8.55(d,J=4.7Hz,1H),8.08(d,J=7.7Hz,1H),7.79–7.76(m,1H),7.44–7.41(m,3H),7.39(dd,J=7.3,5.1Hz,1H),7.28–7.24(m,3H),7.18(d,J=7.8Hz,1H),6.89–6.87(m,1H),5.39–5.32(m,1H),4.26–4.18(m,2H),3.69–3.57(m,2H),1.23(t,J=7.2Hz,3H).HR-MS(ESI)m / z calcd for:C 23 H 21 BrN 2 NaO 3 80 Se + [M+Na] + 554.9793,found 554.9793.

[0118]

[0119] Ethyl 3-(5-chloro-2-(phenylselanyl)phenyl)-2-(picolinamido)propanoate(3sa). 1 H NMR(600MHz,CDCl 3 )δ=8.59(d,J=8.4Hz,1H),8.56(dd,J=5.1,1.6Hz,1H),8.13(d,J=8.1Hz,1H),7.83–7.80(m,1H),7.42(dd,J=7.5,4.8Hz,1H),7.38–7.34(m,2H),7.28(d,J=8.4Hz,1H),7.27(d,J=2.5Hz),7.05(dd,J=8.4,2.5Hz),7.24–7.23(m,3H),5.12–5.08(m,1H),4.22–4.17(m,2H),3.41(dd,J=14.1,6.5Hz,1H),3.33(dd,J=14.0,8.0Hz,1H),1.23(t,J=7.0Hz,3H).HR-MS(ESI)m / z calcd for:C 23 H 21 ClN 2 NaO 3 80 Se + [M+H] +511.0298,found 511.0300.

[0120]

[0121] Ethyl 3-(2,4-dichloro-6-(phenylselanyl)phenyl)-2-(picolinamido)propanoate(3ta). 1 H NMR(600MHz,CDCl 3 )δ=8.76(d,J=9.0Hz,1H),8.58(dd,J=4.8,1.6Hz,1H),8.10(d,J=7.6Hz,1H),7.82–7.80(m,1H),7.49–7.45(m,2H),7.42(dd,J=7.6,4.6Hz,1H),7.37–7.33(m,1H),7.31(dd,J=8.2,6.3Hz,2H),7.24(d,J=2.1Hz,1H),7.01(d,J=2.1Hz,1H),5.31–5.26(m,1H),4.28–4.18(m,2H),3.59–3.48(m,2H),1.25(t,J=7.2Hz,3H).HR-MS(ESI)m / z calcd for:C 23 H 21 Cl 2 N 2 O 3 80 Se + [M+H] + 523.0089,found523.0092.

[0122]

[0123] N-(1-(2-methyl-6-(phenylselanyl)phenyl)propan-2-yl)picolinamide(3ua). 1 H NMR(600MHz,CDCl 3)δ=8.52(ddd,J=4.8,1.8,0.9Hz,1H),8.30(d,J=8.8Hz,1H),8.14–8.12(m,1H),7.82–7.79(m,1H),7.39(ddd,J=7.6,4.8,1.2Hz,1H),7.37–7.33(m,2H),7.24–7.20(m,3H),7.17(dd,J=7.8,1.5Hz,1H),7.08(d,J=7.4Hz,1H),6.97–6.94(m,1H),4.58–4.53(m,1H),3.29(dd,J=13.9,7.9Hz,1H),3.11(dd,J=13.9,7.1Hz,1H),2.50(s,3H),1.35(d,J=6.6Hz,3H).HR-MS(ESI)m / z calcd for:C 22 H 23 N 2 O 80 Se + [M+H] + 411.0970,found 411.0976.

[0124]

[0125] N-(2-(2-(phenylselanyl)-1H-indol-3-yl)ethyl)picolinamide(3va). 1 H NMR(600MHz,CDCl 3 )δ=8.45(dd,J=4.7,1.4Hz,1H),8.37(s,1H),8.18(d,J=7.6Hz,2H),7.81–7.77(m,1H),7.73(d,J=7.9Hz,1H),7.37(dd,J=7.6,4.7Hz,1H),7.32(d,J=8.2Hz,1H),7.23–7.20(m,1H),7.17(d,J=2.1Hz,1H),7.16(d,J=1.6Hz,1H),7.14–7.12(m,2H),7.11(d,J=4.4Hz,2H),3.75–3.71(m,2H),3.23(t,J=7.2Hz,2H).HR-MS(ESI)m / z calcdfor:C 22 H 19 N 3 NaO 80 Se + [M+Na] +444.0586,found 444.0587.

[0126]

[0127] N-(2-(3-(phenylselanyl)thiophen-2-yl)ethyl)picolinamide(3wa). 1 H NMR(600MHz,CDCl 3 )δ=8.52(d,J=4.9Hz,1H),8.28–8.15(m,2H),7.85–7.82(m,1H),7.42–7.40(m,1H),7.23–7.21(m,3H),7.20–7.11(m,3H),7.04(dd,J=5.3,2.0Hz,1H),3.71–3.68(m,2H),3.29(t,J=7.0Hz,2H).HR-MS(ESI)m / z calcd for:C 18 H 16 N 2 NaOS 80 Se + [M+Na] + 411.0041,found 411.0039.

[0128]

[0129] N-(2-((4-methoxyphenyl)selanyl)-6-methylphenethyl)picolinamide(3ab). 1 H NMR(600MHz,CDCl 3 )δ=8.56(ddd,J=4.8,1.8,0.9Hz,1H),8.30(s,1H),8.23–8.21(m,1H),7.87–7.84(m,1H),7.47–7.45(m,2H),7.43(ddd,J=7.6,4.8,1.3Hz,1H),7.04(ddd,J=7.2,1.6,0.8Hz,1H),7.00–6.97(m,1H),6.97–6.93(m,1H),6.88–6.84(m,2H),3.81(s,3H),3.70–3.64(m,2H),3.21–3.16(m,2H),2.46(s,3H).HR-MS(ESI)m / z calcd for:C 22 H 22 N 2 NaO2 80 Se + [M+Na] + 449.0739,found 449.0739.

[0130]

[0131] N-(2-((4-fluorophenyl)selanyl)-6-methylphenethyl)picolinamide(3ac). 1 HNMR(600MHz,CDCl 3 )δ=8.54(d,J=4.6Hz,1H),8.31–8.29(m,1H),8.21(d,J=7.7Hz,1H),7.86–7.83(m,1H),7.43–7.40(m,3H),7.11(dd,J=7.5,2.6Hz,2H),7.01–6.96(m,3H),3.68–3.63(m,2H),3.19(m,2H),2.48(s,3H).HR-MS(ESI)m / z calcd for:C 21 H 20 FN 2 O 80 Se + [M+H] + 415.0719,found 415.0721.

[0132]

[0133] N-(2-((3-methoxyphenyl)selanyl)-6-methylphenethyl)picolinamide(3ad). 1 H NMR(600MHz,CDCl 3)δ=8.54(ddd,J=4.8,1.7,0.9Hz,1H),8.26(s,1H),8.21–8.20(m,1H),7.86–7.83(m,1H),7.42(ddd,J=7.6,4.7,1.3Hz,1H),7.28(dd,J=7.7,1.4Hz,1H),7.18–7.12(m,2H),7.04–7.01(m,1H),6.95–6.94(m,1H),6.93(dd,J=2.6,1.4Hz,1H),6.77(ddd,J=8.3,2.5,1.0Hz,1H),3.74(s,3H),3.65–3.61(m,2H),3.23–3.19(m,2H),2.49(s,3H).HR-MS(ESI)m / z calcd for:C 22 H 23 N 2 O 2 80 Se + [M+H] + 427.0919,found 427.0917.

[0134]

[0135] N-(2-((3-fluorophenyl)selanyl)-6-methylphenethyl)picolinamide(3ae). 1 HNMR(600MHz,CDCl 3 )δ=8.56–8.52(m,1H),8.28–8.26(m,1H),8.20(d,J=8.13Hz,1H),7.86–7.83(m,1H),7.42(dd,J=7.5,4.8Hz,1H),7.34(d,J=7.7Hz,1H),7.21–7.17(m,2H),7.11–7.08(m,1H),7.08–7.05(m,1H),7.01–6.96(m,1H),6.91–6.87(m,1H),3.66–3.59(m,2H),3.23–3.17(m,2H),2.51(s,3H).HR-MS(ESI)m / z calcd for:C 21 H 20 FN 2 O 80 Se + [M+H] + 415.0719,found 415.0718.

[0136]

[0137] N-(2-((3-chlorophenyl)selanyl)-6-methylphenethyl)picolinamide(3af). 1 HNMR(600MHz,CDCl 3 )δ=8.53(dd,J=5.1,1.8Hz,1H),8.28–8.26(m,1H),8.20(d,J=7.8Hz,1H),7.85–7.82(m,1H),7.43–7.40(m,1H),7.32–7.28(m,2H),7.20–7.16(m,3H),7.16–7.13(m,1H),7.07–7.04(m,1H),3.65–3.60(m,2H),3.22–3.18(m,2H),2.50(s,3H).HR-MS(ESI)m / z calcd for:C 21 H 19 ClN 2 NaO 80 Se + [M+Na] + 453.0243,found 453.0240.

[0138]

[0139] N-(2-((3-bromophenyl)selanyl)-6-methylphenethyl)picolinamide(3ag). 1 HNMR(600MHz,CDCl 3 )δ=8.57–8.52(m,1H),8.28(s,1H),8.21(d,J=7.8Hz,1H),7.87–7.84(m,1H),7.48(s,1H),7.45–7.41(m,1H),7.34(d,J=8.1Hz,1H),7.29(d,J=7.9Hz,1H),7.23(d,J=7.9Hz,1H),7.18(d,J=7.6Hz,1H),7.10–7.05(m,2H),3.64–3.60(m,2H),3.21(t,J=7.9Hz,2H),2.51(s,3H).HR-MS(ESI)m / z calcd for:C 21 H 20 BrN 2 O 80 Se +[M+H] + 474.9919,found 474.9921.

[0140]

[0141] N-(2-methyl-6-(o-tolylselanyl)phenethyl)picolinamide(3ah). 1 H NMR(600MHz,CDCl 3 )δ=8.54(d,J=4.7Hz,1H),8.31(s,1H),8.22(d,J=7.8Hz,1H),7.87–7.85(m,1H),7.43(dd,J=7.7,5.0Hz,1H),7.24–7.21(m,1H),7.17(dd,J=7.8,5.8Hz,2H),7.11(d,J=7.6Hz,1H),7.07(d,J=7.7Hz,1H),7.05–7.02(m,1H),7.00–6.97(m,1H),3.67–3.63(m,2H),3.21–3.16(m,2H),2.49(s,3H),2.39(s,3H).HR-MS(ESI)m / z calcd for:C 22 H 23 N 2 O 80 Se + [M+H] + 411.0970,found 411.0970.

[0142]

[0143] N-(2-((2-methoxyphenyl)selanyl)-6-methylphenethyl)picolinamide(3ai). 1 H NMR(600MHz,CDCl 3)δ=8.53–8.52(m,1H),8.31–8.15(m,2H),7.85–7.82(m,1H),7.45–7.40(m,2H),7.24–7.20(m,1H),7.16(d,J=2.5Hz,1H),7.08(d,J=3.0Hz,1H),6.85(dd,J=8.4,2.9Hz,1H),6.80–6.72(m,2H),3.92(s,3H),3.64–3.60(m,2H),3.25–3.18(m,2H),2.54(s,3H).HR-MS(ESI)m / z calcd for:C 22 H 22 N 2 NaO 2 80 Se + [M+Na] + 449.0739,found449.0737.

[0144]

[0145] N-(2-((2-bromophenyl)selanyl)-6-methylphenethyl)picolinamide(3aj). 1 HNMR(600MHz,CDCl 3 )δ=8.53(d,J=4.9Hz,1H),8.28–8.26(m,1H),8.18(d,J=7.7Hz,1H),7.85–7.82(m,1H),7.49(d,J=7.6Hz,2H),7.41(dd,J=7.6,4.7Hz,1H),7.28(d,J=7.6Hz,1H),7.15–7.12(m,1H),7.09–6.99(m,2H),6.69(d,J=7.6Hz,1H),3.65–3.58(m,2H),3.21–3.18(m,2H),2.56(s,3H).HR-MS(ESI)m / z calcd for:C 21 H 20 BrN 2 O 80 Se + [M+H] + 474.9919,found 474.9918.

[0146]

[0147] N-(2-(2-(phenylselanyl)cyclohex-1-en-1-yl)ethyl)picolinamide(3xa). 1 HNMR(600MHz,CDCl 3 )δ=8.52(d,J=4.7Hz,1H),8.20–8.15(m,2H),7.84–7.82(m,1H),7.41–7.39(m,1H),7.36(d,J=6.7Hz,2H),7.19(d,J=5.9Hz,3H),3.61–3.58(m,2H),2.73(t,J=7.3Hz,2H),2.30(d,J=6.5Hz,2H),2.25(d,J=6.8Hz,2H),1.70–1.66(m,2H),1.62–1.58(m,2H).HR-MS(ESI)m / z calcd for:C 20 H 22 N 2 NaO 80 Se + [M+Na] + 409.0790,found 409.0789.

[0148]

[0149] N-(2-(2-((4-methoxyphenyl)selanyl)cyclohex-1-en-1-yl)ethyl)picolinamide(3xb). 1 H NMR(600MHz,CDCl 3 )δ=8.55(dd,J=4.8,1.6Hz,1H),8.22(d,J=7.6Hz,2H),7.88–7.85(m,1H),7.44(dd,J=7.7,4.7Hz,1H),7.39–7.34(m,2H),6.77(d,J=8.9Hz,2H),3.78(s,3H),3.63–3.57(m,2H),2.71(t,J=7.3Hz,2H),2.25(t,J=6.2Hz,2H),2.12(t,J=6.2Hz,2H),1.67–1.62(m,2H),1.59–1.53(m,2H).HR-MS(ESI)m / z calcd for:C 21 H 24 N 2 NaO 2 80 Se + [M+Na]+ 439.0895,found 439.0895.

[0150]

[0151] N-(2-(2-((4-fluorophenyl)selanyl)cyclohex-1-en-1-yl)ethyl)picolinamide(3xc). 1 H NMR(600MHz,CDCl 3 )δ=8.53(d,J=4.9Hz,1H),8.24–8.15(m,2H),7.86–7.84(m,1H),7.43(dd,J=7.4,5.0Hz,1H),7.35(dd,J=8.4,5.4Hz,2H),6.91–6.88(m,2H),3.62–3.58(m,2H),2.72(t,J=7.3Hz,2H),2.29(t,J=6.3Hz,2H),2.17(t,J=6.5Hz,2H),1.69–1.65(m,2H),1.60–1.56(m,2H).HR-MS(ESI)m / z calcd for:C 20 H 21 FN 2 NaO 80 Se + [M+Na] + 427.0695,found 427.0697.

[0152]

[0153] N-(2-(2-((3-methoxyphenyl)selanyl)cyclohex-1-en-1-yl)ethyl)picolinamide(3xd). 1 H NMR(600MHz,CDCl 3)δ=8.52(ddd,J=4.8,1.7,0.9Hz,1H),8.19–8.18(m,1H),8.15(s,1H),7.85–7.82(m,1H),7.40(ddd,J=7.6,4.8,1.2Hz,1H),7.11(dd,J=8.2,7.6Hz,1H),6.94(ddd,J=7.6,1.6,0.9Hz,1H),6.91(dd,J=2.6,1.5Hz,1H),6.72(ddd,J=8.3,2.6,0.9Hz,1H),3.76(s,3H),3.62–3.56(m,2H),2.72(t,J=7.3Hz,2H),2.34–2.30(m,2H),2.29–2.27(m,2H),1.71–1.66(m,2H),1.64–1.59(m,2H).HR-MS(ESI)m / zcalcd for:C 21 H 24 N 2 NaO 2 80 Se + [M+Na] + 439.0895,found 439.0895.

[0154]

[0155] N-(2-(2-((3-fluorophenyl)selanyl)cyclohex-1-en-1-yl)ethyl)picolinamide(3xe). 1 H NMR(600MHz,CDCl 3 )δ=8.52(d,J=4.8Hz,1H),8.20–8.13(m,2H),7.86–7.82(m,1H),7.42(dd,J=7.6,4.8Hz,1H),7.17–7.09(m,2H),7.05–7.01(m,1H),6.87–6.84(m,1H),3.61-3.58(m,2H),2.72(t,J=7.3Hz,2H),2.34(t,J=6.1Hz,2H),2.27(t,J=6.2Hz,2H),1.73–1.67(m,2H),1.65–1.61(m,2H).HR-MS(ESI)m / z calcd for:C 20 H 21 FN 2 NaO 80 Se + [M+Na]+ 427.0695,found 427.0697.

[0156]

[0157] N-(2-(2-((2-methoxyphenyl)selanyl)cyclohex-1-en-1-yl)ethyl)picolinamide(3xi). 1 H NMR(600MHz,CDCl 3 )δ=8.51(d,J=4.8Hz,1H),8.19(d,J=7.7Hz,2H),7.87–7.84(m,1H),7.42(dd,J=7.6,4.9Hz,1H),7.16–7.11(m,1H),7.09–7.05(m,1H),6.81–6.79(m,2H),3.87(s,3H),3.60–3.56(m,2H),2.72(t,J=7.5Hz,2H),2.38–2.33(m,4H),1.73(dd,J=6.9,4.8Hz,2H),1.69–1.63(m,2H).HR-MS(ESI)m / z calcd for:C 21 H 24 N 2 NaO 2 80 Se + [M+Na] + 439.0895,found 439.0896.

[0158]

[0159] N-(2-(2-((2-fluorophenyl)selanyl)cyclohex-1-en-1-yl)ethyl)picolinamide(3xk). 1 H NMR(600MHz,CDCl 3)δ=8.49(d,J=4.7Hz,1H),8.20–8.09(m,2H),7.82–7.80(m,1H),7.39(dd,J=7.9,4.5Hz,1H),7.22–7.20(m,1H),7.16–7.13(m,1H),7.00–6.79(m,1H),6.95–6.93(m,1H),3.59–3.56(m,2H),2.71(t,J=7.3Hz,2H),2.31(t,J=6.2Hz,2H),2.22(t,J=6.3Hz,2H),1.68–1.65(m,2H),1.62–1.59(m,2H).HR-MS(ESI)m / zcalcd for:C 20 H 21 FN 2 NaO 80 Se + [M+Na] + 427.0695,found 427.0695.

[0160]

[0161] (E)-N-(3-phenyl-4-(phenylselanyl)but-3-en-1-yl)picolinamide(3ya). 1 HNMR(600MHz,CDCl 3 )δ=8.52–8.48(m,1H),8.22–8.18(m,2H),7.85–7.82(m,1H),7.50(dd,J=7.5,2.1Hz,2H),7.45(d,J=7.5Hz,2H),7.40(dd,J=7.6,4.9Hz,1H),7.34–7.32(m,2H),7.29–7.27(m,2H),7.27–7.24(m,2H),6.88(s,1H),3.62–3.59(m,2H),3.05(t,J=7.2Hz,2H).HR-MS(ESI)m / z calcd for:C 22 H 21 N 2 O 80 Se + [M+H] + 409.0814,found 409.0814.

[0162]

[0163] (E)-N-(3-(4-fluorophenyl)-4-(phenylselanyl)but-3-en-1-yl)picolinamide(3za). 1 H NMR (600 MHz, CDCl 3 )δ=8.51(d,J=4.7Hz,1H),8.21(dd,J=19.5,6.9Hz,2H),7.86–7.83(m,1H),7.50(dd,J=6.6,3.0Hz,2H),7.43–7.42(m,1H),7.42–7. 39(m,2H),7.28(dd,J=4.9,2.0Hz,3H),7.02–6.99(m,2H),6.81(s,1H),3.59(q,J=6.7Hz,2H),3.02(t,J=7.2Hz,2H).HR-MS(ESI)m / z calcd for:C 22 H 20 FN 2 O 80 Se + [M+H] + 427.0719, found 427.0719.

[0164] The above contents are further detailed descriptions of the present invention in combination with specific implementation methods, and it cannot be determined that the specific implementation methods of the present invention are limited to these descriptions. For ordinary technicians in the technical field to which the present invention belongs, several deductions or substitutions can be made without departing from the concept of the present invention, which should be regarded as falling within the scope of protection of the present invention.

Claims

1. A method for preparing compound III, characterized in that: Compound I and Compound II are reacted with a palladium catalyst and an oxidant in a solvent to obtain Compound III; wherein the structural formulas of Compound I, Compound II and Compound III are as follows: Wherein, the compound I is selected from one of the following structural formulas: ； Wherein, the compound II is selected from one of the following structural formulas: ； Wherein, the compound III is selected from one of the following structural formulas: ; The palladium catalyst is Pd(OAc)2; The oxidant is one or more of AgOAc, Ag2CO3, AgOPiv, and PhI(OAc)2; The solvent is one or more of toluene, 1,4-dioxane, acetonitrile, and 1,2-dichloroethane.

2. The method for preparing compound III according to claim 1, characterized in that: The molar ratio of compound I to compound II is 1:1-10; the added palladium catalyst is 1-10 mol%; and the molar ratio of compound I to oxidant is 1:1-10.

3. The method for preparing compound III according to claim 2, characterized in that: The method comprises mixing compound I, compound II, palladium catalyst, oxidant and solvent for direct reaction under an inert gas, and the reaction temperature is 100-140°C.

4. The method for preparing compound III according to claim 3, characterized in that: The reaction temperature was 120°C.

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