Antimony aryl compound as well as synthesis method and application thereof
Through the cross-coupling reaction of Ni/Pd synergistic catalyst, the problem of insufficient applicability of antimony aryl compounds to sensitive functional groups in the prior art was solved, and a variety of antimony aryl compounds were achieved efficiently synthesis, especially compatibility with ester groups, cyano groups and sulfide groups was achieved. The product showed significant effects in biological activity tests.
Patent Information
- Application Number
- CN202510579808.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-07
- Publication Date
- 2025-08-08
AI Technical Summary
The prior art is difficult to effectively construct antimony aryl compounds containing sensitive functional groups such as amide groups through cross-coupling reactions, and the interaction between aryl esters and metal catalysts is weak, which limits the applicability of the antimonylation reaction.
The bimetallic catalyst Ni/Pd is used to synergize the cross-coupling reaction of triflate and organic antimony halogen. The reaction is carried out in the NMP solvent by Ni(dppp)Cl2 and XPhos Pd G3 as catalysts, zinc powder as reducing agents, and lithium bromide as additives, and high-efficiency conversion of Ar-OTf substrates with different groups is achieved.
Compatibility with sensitive functional groups such as ester groups, cyano groups and sulfide groups was achieved, with 35 products, and the yield rate of gram-level amplification reaction was high, and the target product showed a strong inhibitory effect in the biological activity test.
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Figure CN120441621A_ABST
Abstract
Description
Technical field
[0001] The invention belongs to the field of synthesis of metal antimony aryl reagents, and in particular relates to an antimony aryl compound and a synthesis method and application thereof. [Background Technology]
[0002] Organoantimony compounds are important reagents for organic synthesis. Our research group has demonstrated for the first time the use of metal catalysis to achieve cross-coupling reactions of arylantimony chlorides with arylboronic acids and halogenated hydrocarbons to construct antimony aryl / alkyl compounds. However, some functional groups, such as amide groups, remain incompatible. Therefore, further expanding the range of coupling reagents to accommodate a wider range of functional groups is an important step in constructing an organoantimony library. Furthermore, compared to aryl halides, the interaction between Ar-OTf and the metal center is weaker after oxidative addition with metal catalysts. Therefore, developing a catalytic synthesis strategy using Ar-OTf as a substrate is more efficient.
[0003] Triflate is an excellent leaving group because it has a high electronegativity and good leaving ability, which enables it to effectively participate in many chemical reactions and form new chemical bonds. However, these groups themselves have a strong electronegativity, which makes them difficult to be replaced or broken in some cases. After being converted into aryl triflate, phenol can be used as a cross-coupling partner through the cleavage of the CO bond in a transition metal-catalyzed cross-coupling reaction to construct a variety of CC (Journal of Organic Chemistry, 1993, 58: 997-998.), CN (Journal of the American Chemical Society, 2019, 141: 6755-6764.), CS (Journal of the American Chemical Society, 2006, 128: 2180-2181.), C-Se (Tetrahedron, 2005, 61: 5253-5259.) and other bonds. Like the C (sp) in aryl esters and ethers 2 )-O bonds have become a powerful alternative to CX (X=Cl, Br, I) bonds (such as those in aryl halides) in cross-coupling chemistry.
[0004] Therefore, the present invention has developed a bimetallic catalyzed cross-coupling reaction of trifluoromethanesulfonate and organoantimony to generate organoantimony aryl. This reaction uses trifluoromethanesulfonate and organoantimony chloride as raw materials, and realizes the transformation from aryl trifluoromethanesulfonate to organoantimony aryl. The catalytic system shows excellent compatibility with sensitive functional groups such as ester, cyano and thioether groups, and the number of products reaches 35, breaking through the bottleneck of traditional antimonization reaction on polar groups. It performs well in gram-scale amplification reactions and can obtain our target product with a medium to high yield. Among them, the 3p compound performs well in biological activity tests and has a strong inhibitory effect on breast cancer cells. Organoantimony aryl compounds can also be used as ligands to regulate the hydrogenation reaction of diphenylacetylene, realizing precise control of chemical conversion selectivity. [Summary of the invention]
[0005] We have developed a novel reaction pathway for trifluoromethanesulfonates with organoantimony halides, a general method for the efficient synthesis of a series of antimony aryls via a dual-catalyst-mediated cross-coupling reaction. This method can provide cross-coupling products in high yields. This is the first example of a C-O bond cleavage to form a C-Sb bond. We have expanded the substrate scope to include Ar-OTf with different substituents, exploring chlorides and bromides, as well as substrate applicability to a variety of functional groups (including nitriles, esters, and ethers). Trifluoromethanesulfonate substrates with different substituents can provide our target products in moderate to high yields, indicating that this synthetic strategy has strong application value. A method for synthesizing antimony aryl compounds through a Ni / Pd-catalyzed antimony arylation reaction, the structural formula of which is as follows:
[0006]
[0007] Wherein Ar in the compound I is selected from 4-methylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 4-cyclohexylphenyl, 3-methylphenyl, 3-tert-butylphenyl, 2-methylphenyl, 4-biphenyl, 4-phenoxyphenyl, 4-(methylthio)phenyl, 4-methoxyphenyl, 4-fluorophenyl, 3-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-(trifluoromethyl)phenyl, 4-trifluoromethylsulfonyl, 4-acetylphenyl, 4-cyanophenyl, 4-(trifluoromethylthio)phenyl, 2-naphthyl, 6-cyano-2-naphthyl, 3,5-dimethylphenyl, 3,5-dimethoxyphenyl, 3,5-di-tert-butylphenyl, 4-acetamidophenyl, benzo[D][1.3]dioxolyl. wherein the R group is selected from the group consisting of: 4-methyl, 4-isopropyl, 4-cyclohexyl, 3-methyl, 2-methyl, 4-phenoxy, 4-methylthio, 4-methoxy, 4-fluoro, 4-chloro, 3-chloro, 4-trifluoromethyl, 4-tri-tert-butyl ester, 4-acetyl, 4-trifluoromethylthio, 2-naphthyl, 6-cyano-2-naphthyl, 3,5-dimethoxyphenyl, H, 2,3-benzo[d][1,3]dioxolane, (8R,9S,13S)- 13-Methyl-3-(6-phenyl-6,7-dihydrodibenzo[c,f][1,5]-12(5H)-yl)-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthrene-17-one, 4-methylthio, etc., with organic antimony chloride compound II and trifluoromethanesulfonate III as raw materials, N-methylpyrrolidone (2 mL), Ni(dppp)Cl2 (0.005 mmol), XPhos Pd G3 (0.005 mmol, 5 mol%), zinc powder (0.2 mmol, 2.0 eq.), LiBr (0.2 mmol, 2.0 eq.), reacted at different temperatures for 12 h under N2 atmosphere to obtain our target product. The structural formulas of antimony chloride (II) and triflate (III), Ni(dppp)Cl2, XPhos Pd G3, are as follows:
[0008]
Brief Description of the Drawings
[0009] Figure 1 This is a method roadmap for synthesizing antimony aryl compounds through a Ni / Pd synergistically catalyzed antimony arylation reaction provided by the present invention.
[0010] Figure 2 This is a graph showing the results of a test on the inhibition of breast cancer by the product of the present invention;
[0011] Figure 3 is the hydrogen spectrum of compound 3p;
[0012] Figure 4 is the carbon spectrum of compound 3p. [Specific implementation method]
[0013] To further expand the range of coupling reagents, this study selected N-Ph-substituted aryl antimony chloride II and p-methylthio-substituted triflate III as raw materials, Ni(dppp)Cl2 and XPhos Pd G3 as synergistic catalysts, zinc powder as a reducing agent, lithium bromide as an additive, and NMP as a solvent. The reaction conditions were 100°C for 12 hours under a nitrogen atmosphere. After completion, the desired product was isolated by column chromatography.
[0014] The present invention will be further described below with reference to specific preparation examples:
[0015] Preparation Example 1
[0016] To a 10 mL Schlenk tube equipped with a magnetic stirrer, arylantimony chloride 1a (0.1 mmol), triflate III (R = 4-methyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder, concentrated under reduced pressure, and purified by column chromatography to afford 6-phenyl-12-(p-tolyl)-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3b) as a white solid in 82% yield.
[0017] Preparation Example 2
[0018] To a 10 mL Schlenk tube equipped with a magnetic stirrer, arylantimony chloride 1a (0.1 mmol), triflate III (R = 4-isopropyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL of NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder, concentrated under reduced pressure, and purified by column chromatography to yield 12-(4-isopropylphenyl)-6-phenyl-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3d) as a white solid in 71% yield.
[0019] Preparation Example 3
[0020] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), trifluoromethanesulfonate III (R = 4-cyclohexylphenyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol) and 2.0 mL NMP were added in sequence. The reaction tube was filled with nitrogen and then placed in an oil bath at 100°C and stirred for 12 h. After the reaction was completed, the reaction solution was added with silica gel powder and concentrated under reduced pressure, and purified by chromatography to obtain
[0021] 12-(4-cyclohexylphenyl)-6-phenyl-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3f) was obtained as a white solid in 50% yield.
[0022] Preparation Example 4
[0023] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), trifluoromethanesulfonate III (R = 3-methylphenyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol) and 2.0 mL NMP were added in sequence. The reaction tube was filled with nitrogen and then placed in an oil bath at 100°C and stirred for 12 h. After the reaction was completed, the reaction solution was added with silica gel powder and concentrated under reduced pressure, and purified by chromatography to obtain
[0024] 6-phenyl-12-(m-tolyl)-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3 g), white solid, yield 60%.
[0025] Preparation Example 5
[0026] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), triflate III (R = 2-methylphenyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder, concentrated under reduced pressure, and purified by column chromatography to yield 6-phenyl-12-(o-tolyl)-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3i) as a white solid in 63% yield.
[0027] Preparation Example 6
[0028] To a 10 mL Schlenk tube equipped with a magnetic stirrer were added arylantimony chloride 1a (0.1 mmol), triflate III (R = 4-phenoxyphenyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL NMP. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder, concentrated under reduced pressure, and purified by column chromatography to yield 12-(4-phenoxyphenyl)-6-phenyl-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3k) as a white solid in 43% yield.
[0029] Preparation Example 7
[0030] To a 10 mL Schlenk tube equipped with a magnetic stirrer were added arylantimony chloride 1a (0.1 mmol), triflate III (R = 4-(methylthio)phenyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL NMP. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder and concentrated under reduced pressure. Purification by column chromatography afforded 12-(4-(methylthio)phenyl)-6-phenyl-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3l) as a white solid in a 92% yield.
[0031] Preparation Example 8
[0032] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), triflate III (R = 4-methoxyphenyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder, concentrated under reduced pressure, and purified by column chromatography to afford 1-(4-(6-phenyl-6,7-dihydrodibenzo[c,f][1,5]azastibocin-12(5H)-yl)phenyl)ethan-1-o (3 m) as a white solid in a 64% yield.
[0033] Preparation Example 9
[0034] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), triflate III (R = 4-fluoro) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL of NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder and concentrated under reduced pressure. Purification by column chromatography afforded 12-(4-fluorophenyl)-6-phenyl-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3n) as a white solid in a 67% yield.
[0035] Preparation Example 10
[0036] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), triflate III (R = 4-chloro) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL of NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder, concentrated under reduced pressure, and purified by column chromatography to yield 12-(4-chlorophenyl)-6-phenyl-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine(3p) as a white solid in a 62% yield.
[0037] Preparation Example 11
[0038] To a 10 mL Schlenk tube equipped with a magnetic stirrer were added arylantimony chloride 1a (0.1 mmol), triflate III (R = 3-chloro) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL of NMP. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder, concentrated under reduced pressure, and purified by column chromatography to yield 12-(2-chlorophenyl)-6-phenyl-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3q) as a white solid in a 65% yield.
[0039] Preparation Example 12
[0040] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), triflate III (R = 4-trifluoromethyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder, concentrated under reduced pressure, and purified by column chromatography to yield 6-phenyl-12-(4-(trifluoromethyl)phenyl)-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3r) as a white solid in 65% yield.
[0041] Preparation Example 13
[0042] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), triflate III (R = 4-tri-tert-butyl ester) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder and concentrated under reduced pressure. Tert-butyl 4-(6-phenyl-6,7-dihydrodibenzo[c,f][1,5]azastibocin-12(5H)-yl)benzoate (3s) was obtained as a white solid in a 65% yield.
[0043] Preparation Example 14
[0044] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), trifluoromethanesulfonate III (R = 4-acetyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol) and 2.0 mL NMP were added in sequence. The reaction tube was filled with nitrogen and then placed in an oil bath at 100°C and stirred for 12 h. After the reaction was completed, the reaction solution was added with silica gel powder and concentrated under reduced pressure, and purified by chromatography to obtain
[0045] 1-(4-(6-phenyl-6,7-dihydrodibenzo[c,f][1,5]azastibocin-12(5H)-yl)phenyl)ethan-1-one(3t), white solid, yield 48%.
[0046] Preparation Example 15
[0047] To a 10 mL Schlenk tube equipped with a magnetic stirrer were added arylantimony chloride 1a (0.1 mmol), triflate III (R = 4-trifluoromethylthio) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL of NMP. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder, concentrated under reduced pressure, and purified by column chromatography to yield 6-phenyl-12-(4-((trifluoromethyl)thio)phenyl)-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3v) as a white solid in 38% yield.
[0048] Preparation Example 16
[0049] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), triflate III (R = 2-naphthyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL of NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder and concentrated under reduced pressure. Purification by column chromatography afforded 12-(naphthalen-2-yl)-6-phenyl-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3w) as a white solid in a 62% yield.
[0050] Preparation Example 17
[0051] To a 10 mL Schlenk tube equipped with a magnetic stirrer were added arylantimony chloride 1a (0.1 mmol), triflate III (R = 6-cyano-2-naphthyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL of NMP. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder and concentrated under reduced pressure. Purification by column chromatography afforded 6-(6-phenyl-6,7-dihydrodibenzo[c,f][1,5]azastibocin-12(5H)-yl)naphthalen-2-amine (3x) as a white solid in a 63% yield.
[0052] Preparation Example 18
[0053] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), triflate III (R = 3,5-dimethoxyphenyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder and concentrated under reduced pressure. Purification by column chromatography afforded 12-(3,5-dimethoxyphenyl)-6-phenyl-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3z) as a white solid in a 39% yield.
[0054] Preparation Example 19
[0055] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1a (0.1 mmol), triflate III (R=H) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After the reaction, the reaction solution was added to silica gel powder and concentrated under reduced pressure. Purification by column chromatography afforded 12-(3,5-di-tert-butylphenyl)-6-phenyl-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3a) as a white solid in 28% yield.
[0056] Preparation Example 20
[0057] To a 10 mL Schlenk tube equipped with a magnetic stirrer were added arylantimony chloride 1a (0.1 mmol), triflate III (R = 2,3-benzo[d][1,3]dioxolyl) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL NMP. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder and concentrated under reduced pressure. Purification by column chromatography afforded 12-(benzo[d][1,3]dioxol-5-yl)-6-phenyl-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3ac) as a white solid in 67% yield.
[0058] Preparation Example 21
[0059] To a 10 mL Schlenk tube equipped with a magnetic stirrer, arylantimony chloride 1a (0.1 mmol), triflate III (R = (8R,9S,13S)-13-methyl-3-(6-phenyl-6,7-dihydrodibenzo[c,f][1,5]-12(5H)-yl)-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthrene-17-one) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL of NMP were added in sequence. The reaction tube was filled with nitrogen and placed in an oil bath at 100°C with stirring for 12 h. After the reaction, the reaction solution was added with silica gel powder and concentrated under reduced pressure. The product was purified by column chromatography to obtain (8R,9S,13S)-13-methyl-3-(6-phenyl-6,7-dihydrodibenzo[c,f][1,5]azastibocin-12(5H)-yl)-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one(3ad) as a white solid in a yield of 54%.
[0060] Preparation Example 22
[0061] To a 10 mL Schlenk tube equipped with a magnetic stirrer, aryl antimony chloride 1b (0.1 mmol), triflate III (R = 4-methylthio) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL NMP were added sequentially. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder and concentrated under reduced pressure. Purification by column chromatography afforded 6-(4-methoxyphenyl)-12-(4-(methylthio)phenyl)-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3ae) as a white solid in a 64% yield.
[0062] Preparation Example 23
[0063] To a 10 mL Schlenk tube equipped with a magnetic stirrer were added arylantimony chloride 1c (0.1 mmol), triflate III (R = 4-methylthio) (0.15 mmol), XPhos Pd G3 (0.05 mmol), Ni(dppe)Cl2 (0.05 mmol), Zn powder (0.2 mmol), LiBr (0.2 mmol), and 2.0 mL of NMP. The reaction tube was filled with nitrogen and stirred in an oil bath at 100°C for 12 h. After completion of the reaction, the reaction solution was added to silica gel powder and concentrated under reduced pressure. Purification by column chromatography afforded 12-(4-(methylthio)phenyl)-6-(4-(trifluoromethyl)phenyl)-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (3af) as a white solid in 84% yield.
[0064] The following is a further description of the present invention in combination with the test of antimony aryl compounds on different cancer cells:
[0065] Experimental steps: We tested the effect of organoantimony compounds on the activity of the human breast cancer cell line MDA-MB-231. Breast cancer cells were cultured in Gibco's Dulbecco's modified Eagle's medium (DMEM), which was supplemented with 10% fetal bovine serum containing L-glutamine and 1% penicillin-streptomycin from HyClone. The cells were cultured in a humidified incubator containing 95% air and 5% carbon dioxide, and the temperature was maintained at 37°C. From the analysis of the experimental data, it can be seen that most of the aromatic antimony compounds have no obvious inhibitory effect on the human breast cancer cell line MDA-MB-231, but we can see from Figure 2 The results of the analysis showed that 3p had the highest biological activity.
Claims
1. An antimony aryl compound, characterized in that The structure of the antimony aryl compound is as follows:
2. Use of an antimony aryl compound, characterized in that: The antimony aryl compound as claimed in claim 1 is used for preparing a drug for treating cancer, including breast cancer.
3. A method for synthesizing an antimony aryl compound, characterized in that: Using organoantimony chloride II and triflate III as raw materials, Ni(dppp)Cl2 and XPhos Pd G3 as catalysts, zinc powder as a reducing agent, lithium bromide as an additive, and NMP as a solvent, the reaction is carried out at 100°C for 12 hours under a nitrogen environment to obtain a reaction solution containing the antimony aryl compound; The chemical structure of organoantimony chloride compound II is: The chemical structural formula of trifluoromethanesulfonate III is: The chemical formula of Ni(dppp)Cl2 is: The chemical structure of XPhos Pd G3 is:
4. The method for synthesizing an antimony aryl compound according to claim 3, wherein: Silica gel powder is added to the reaction solution containing the antimony aryl compound, and the mixture is concentrated under reduced pressure, and then purified by a chromatography column to obtain a purified antimony aryl compound.
5. The method for synthesizing an antimony aryl compound according to claim 3, wherein: The molar ratio of the organoantimony chloride II, trifluoromethanesulfonate III, Ni(dppp)Cl2, XPhos Pd G3, zinc powder and lithium bromide is 0.1:0.15:0.05:0.05:0.2:0.2.