阅读说明：本技术 一种n-(氰基(2-氰基取代苯基)甲基)取代的三级胺的合成方法 (Synthesis method of N- (cyano (2-cyano substituted phenyl) methyl) substituted tertiary amine ) 是由 王少华 包文 高珠鹏 于 2020-05-18 设计创作，主要内容包括：本发明属于有机合成技术领域,具体涉及一种N-(氰基(2-氰基取代苯基)甲基)取代的三级胺的合成方法,其反应通式如下：本发明由N,N-二取代氨基-丙二腈和取代2-(三甲基硅)苯基三氟甲烷磺酸酯在催化剂的作用下,发生取代反应合成N-(氰基(2-氰基取代苯基)甲基)取代的三级胺类化合物。该方法所用的起始原料易得,操作简单,反应条件温和,催化剂廉价,能减少资金和劳动力的投入量,为N-(氰基(2-氰基取代苯基)甲基)取代的三级胺衍生物提供一种快捷高效的制备方法。(The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing N- (cyano (2-cyano substituted phenyl) methyl) substituted tertiary amine, which has the following reaction general formula:)

1. A synthetic method of N- (cyano (2-cyano substituted phenyl) methyl) substituted tertiary amine is characterized in that N, N-disubstituted amino-malononitrile, substituted 2- (trimethylsilyl) phenyl trifluoromethanesulfonate and a catalyst are sequentially added into an organic solvent, and N- (cyano (2-cyano substituted phenyl) methyl) substituted tertiary amine compound is obtained under the heating condition, wherein the reaction formula is as follows:

wherein:

(1)R¹、R²when not in the same ring system, R¹Selected from methyl, n-butyl, benzyl, R²Selected from methyl, substituted phenyl, substituted benzyl;

(2)R¹、R²when on the same ring system, R¹、R²Together with the N atom is selected from piperidinyl, morpholinyl, indolinyl, 1,2,3, 4-tetrahydroisoquinolinyl, 1,2,3, 4-tetrahydroquinolinyl;

(3)R³selected from hydrogen, methyl, methoxy, 4, 5-dimethoxy, 4, 5-methylenedioxy, 4, 5-cyclopentyl;

(4) the catalyst is selected from cesium fluoride + 18-crown-6, cesium fluoride, potassium fluoride + 18-crown-6, potassium fluoride, tetrabutylammonium fluoride, preferably cesium fluoride + 18-crown-6;

(5) the solvent is selected from one or more of acetonitrile, dichloromethane, tetrahydrofuran, diethyl ether, toluene, ethanol, 1, 2-dichloroethane, N-dimethylformamide and 1, 4-dioxane, preferably tetrahydrofuran;

(6) the heating temperature is 0-70 deg.C, and the maintaining time is 1-4 hr, preferably 30 deg.C, and maintaining time is 2 hr;

(7) the molar weight ratio of each substance in the reaction is as follows: n, N-disubstituted amino-malononitrile: substituted 2- (trimethylsilyl) phenyltrifluoromethanesulfonate: catalyst ═ 1:1-2:1.5-3, preferably N, N-disubstituted amino-malononitrile: substituted 2- (trimethylsilyl) phenyltrifluoromethanesulfonate: catalyst 1:1.5: 2.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing N- (cyano (2-cyano substituted phenyl) methyl) substituted tertiary amine.

Background

The polysubstituted benzonitrile is an important chemical skeleton structure, and has wide application in organic synthetic chemistry, pharmaceutical chemistry and pesticide chemistry, such as Perampanel, alogliptin, etravirine and the like. The N- (cyano (2-cyano substituted phenyl) methyl) substituted tertiary amine is an important benzonitrile compound, and because of the amino group, aromatic ring substituent, cyano group and other groups existing in the compound, the polysubstituted benzonitrile compound is easy to generate derivatization reaction, so that the application range of the polysubstituted benzonitrile compound is further expanded. At present, the existing synthetic literature for the compounds firstly prepares halogenated aromatic hydrocarbon and then reacts with cuprous cyanide to obtain products, and the defects are as follows: the reaction conditions are harsh, the operating procedures are cumbersome and highly toxic compounds are required to participate in the reaction (org. biomol. chem.,2012,10, 8539). The invention creatively adds N, N-disubstituted amino-malononitrile, substituted 2- (trimethylsilyl) phenyl trifluoromethanesulfonate and a catalyst into an organic solvent in sequence, and obtains the N- (cyano (2-cyano substituted phenyl) methyl) substituted tertiary amine compound under the heating condition. The synthesis method has the advantages of easily available raw materials, simple operation, mild reaction conditions and wide substrate applicability, and overcomes many defects of the existing preparation method. Therefore, the invention has good practical value and social and economic efficiency, and has good reference significance for the process development of similar products and downstream products.

Disclosure of Invention

The invention aims to overcome the defects of the prior preparation technology and provide a method for synthesizing N- (cyano (2-cyano substituted phenyl) methyl) -substituted tertiary amine compounds, which has the advantages of simple and easily obtained starting materials, high yield and convenient operation.

The technical scheme of the invention is as follows: a synthetic method of N- (cyano (2-cyano substituted phenyl) methyl) substituted tertiary amine compounds is characterized in that N, N-disubstituted amino-malononitrile, substituted 2- (trimethylsilyl) phenyl trifluoromethanesulfonate and a catalyst are sequentially added into an organic solvent, and the N- (cyano (2-cyano substituted phenyl) methyl) substituted tertiary amine compounds are obtained under the heating condition, wherein the reaction formula is as follows:

wherein:

(1)R¹、R²when not in the same ring system, R¹Selected from methyl, n-butyl, benzyl, R²Selected from methyl, substituted phenyl, substituted benzyl;

(2)R¹、R²when on the same ring system, R¹、R²Together with the N atom is selected from piperidinyl, morpholinyl, indolinyl, 1,2,3, 4-tetrahydroisoquinolinyl, 1,2,3, 4-tetrahydroquinolinyl;

(3)R³selected from hydrogen, methyl, methoxy, 4, 5-dimethoxy, 4, 5-methylenedioxy, 4, 5-cyclopentyl.

(4) The catalyst is selected from cesium fluoride + 18-crown-6, cesium fluoride, potassium fluoride + 18-crown-6, potassium fluoride, tetrabutylammonium fluoride, preferably cesium fluoride + 18-crown-6.

(5) The solvent is selected from one or more of acetonitrile, dichloromethane, tetrahydrofuran, diethyl ether, toluene, ethanol, 1, 2-dichloroethane, N-dimethylformamide, and 1, 4-dioxane, preferably tetrahydrofuran.

(6) The heating temperature is 0-70 deg.C, and the holding time is 1-4 hr, preferably 30 deg.C, and 2 hr.

(7) The molar weight ratio of each substance in the reaction is as follows: n, N-disubstituted amino-malononitrile: substituted 2- (trimethylsilyl) phenyltrifluoromethanesulfonate: catalyst ═ 1:1-2:1.5-3, preferably N, N-disubstituted amino-malononitrile: substituted 2- (trimethylsilyl) phenyltrifluoromethanesulfonate: catalyst 1:1.5: 2.

Detailed Description

The present invention will be further described with reference to specific examples, but it should not be construed that the scope of the above-described subject matter of the present invention is limited to the following examples, and that all the technologies implemented based on the above-described contents of the present invention belong to the scope of the present invention.

Examples

1. Indolylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate as starting materials (reaction formula 1)

Indolylamino-malononitrile (100mg, 0.55mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (244mg, 0.82mmol), cesium fluoride (165mg, 1.09mmol) and 18-crown-6 (289mg, 1.09mmol) were added in succession to stirred tetrahydrofuran (2mL) under argon protection in a 10mL reaction tube, the reaction was completed at 30 ℃ for 2 hours, the solvent was drained on a rotary evaporator and a white solid (106mg, 75% yield) was obtained by column chromatography.

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.91(d,J＝7.6Hz,1H),7.79(d,J＝7.6Hz,1H),7.73(t,J＝7.6Hz, 1H),7.57(t,J＝7.6Hz,1H),7.17(t,J＝7.2Hz,2H),6.87(t,J＝7.2Hz,1H),6.78(d,J＝8.0Hz, 1H),5.97(s,1H),3.44-3.37(m,1H),3.17-3.12(m,1H),3.09-3.02(m,1H),3.00-2.91(m,1H)；¹³C NMR(100MHz,CDCl₃)δ148.29,136.49,134.18,133.05,130.40,129.85,128.54,127.56,125.01, 121.06,116.26,114.37,112.71,108.86,53.50,50.40,28.03；HRMS(ESI)calcd for C₁₇H₁₃N₃ [M+H]⁺260.1182, found 260.1190; melting range: 195-197 deg.c.

2. Using N-phenyl-N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate as raw materials (reaction formula 2)

N-phenyl-N-methylamino-malononitrile (200mg, 1.17mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (523mg, 1.75mmol), cesium fluoride (532mg, 3.50mmol) were added in succession to stirred tetrahydrofuran (2mL) in a 10mL reaction tube under argon protection, reacted at 40 ℃ for 2 hours to complete the reaction, the solvent was drained on a rotary evaporator and the column chromatography gave a white solid (196mg, 68% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.85-7.80(m,2H),7.73-7.69(m,1H),7.56(t,J＝8.0Hz,1H),7.36 (t,J＝8.8Hz,2H),7.25(d,J＝8.0Hz,2H),7.07(t,J＝7.6Hz,1H),5.93(s,1H),2.70(s,3H)；¹³C NMR(100MHz,CDCl₃)δ148.72,136.68,134.48,132.95,129.84,129.41,129.35,123.04,119.05, 116.70,114.54,112.51,59.31,35.16；HRMS(ESI)calcd for C₁₆H₁₃N₃[M+H]⁺248.1182, found 248.1185; melting range: 167 ℃ -169 ℃.

3. Starting from N- (4-methylphenyl) -N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (reaction scheme 3)

N- (4-methylphenyl) -N-methylamino-malononitrile (1000mg, 5.40mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (1611mg, 5.40mmol), potassium fluoride (784mg, 13.50mmol) and 18-crown-6 (3567mg, 13.50mmol) were added in succession to stirred acetonitrile (10mL) under argon, reacted at 50 ℃ for 4 hours to complete the reaction, the solvent was drained on a rotary evaporator and the column chromatographed to give a white solid (861mg, 61% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.83-7.80(m,2H),7.72-7.68(m,1H),7.58-7.54(m,1H),7.17(s, 4H),5.85(s,1H),2.67(s,3H),2.32(s,3H)；¹³C NMR(100MHz,CDCl₃)δ146.50,136.83,134.41, 132.94,132.89,129.94,129.77,129.36,119.65,116.77,114.58,112.62,59.98,35.51,20.64； HRMS(ESI)calcd for C₁₇H₁₅N₃[M+H]⁺262.1339, found 262.1342, melting range: 116-117 ℃.

4. Starting from N- (2-methylphenyl) -N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (reaction scheme 4)

N- (2-methylphenyl) -N-methylamino-malononitrile (10g, 53.99 g) was charged to a 250mL reaction flask under argon

mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (20.222g, 67.78mmol), potassium fluoride (6.273g, 107.97 mmol) were added in succession to stirred toluene (40mL), reacted at 70 ℃ for 4 hours to complete the reaction, extracted 3 times with ethyl acetate (50mL) and dried, the organic phase obtained by filtration was freed from the solvent on a rotary evaporator and subjected to column chromatography to give a white solid (10.158g, 72% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.72(d,J＝7.6Hz,1H),7.65-7.57(m,2H),7.53-7.46(m,2H),7.21 (t,J＝6.8Hz,1H),7.14-7.06(m,2H),5.55(s,1H),2.75(s,3H),2.15(s,3H)；¹³C NMR(100MHz, CDCl₃)δ147.43,136.97,134.94,133.68,132.63,131.26,129.48,129.11,126.70,125.88,122.30, 116.45,116.24,113.00,58.78,39.99,17.63；HRMS(ESI)calcd for C₁₇H₁₅N₃[M+H]⁺262.1339, found 262.1343, melting range: 94-96 ℃.

5. Starting from N- (4-methoxyphenyl) -N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (reaction scheme 5)

N- (4-methoxyphenyl) -N-methylamino-malononitrile (50mg, 0.25 mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (134mg, 0.45mmol) and tetrabutylammonium fluoride (118mg, 0.45mmol) were added in succession to stirred dichloromethane (2mL) under argon protection in a 10mL reaction tube, reacted at 20 ℃ for 1 hour to complete the reaction, the solvent was drained on a rotary evaporator and the column chromatography gave a white solid (43g, 63% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.82(d,J＝7.6Hz,1H),7.76(d,J＝7.6Hz,1H),7.68(t,J＝7.6Hz, 1H),7.56(t,J＝7.6Hz,1H),7.26(d,J＝8.8Hz,2H),6.89(d,J＝8.8Hz,2H),5.69(s,1H),3.79(s, 3H),2.65(s,3H)；¹³C NMR(100MHz,CDCl₃)δ156.41,142.47,136.83,134.32,132.87,129.77, 129.43,122.59,116.92,114.66,114.53,112.77,61.27,55.43,36.43；HRMS(ESI)calcd for C₁₇H₁₅N₃O[M+H]⁺278.1288, found 278.1293, melting range: 89-90 ℃.

6. Starting from N- (4-fluorophenyl) -N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (reaction scheme 6)

N- (4-fluorophenyl) -N-methylamino-malononitrile (250mg, 1.32) was placed in a 10mL reaction tube under argon

mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (433mg, 1.45mmol), cesium fluoride (442mg, 2.91mmol) and 18-crown-6 (769mg, 2.91mmol) were added in succession to stirred diethyl ether (2mL) and reacted at 0 ℃ for 3 hours to complete the reaction, the solvent was drained on a rotary evaporator and column chromatography was carried out to give a white solid (214mg, 61% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.84-7.79(m,2H),7.71(t,J＝7.6Hz,1H),7.58(t,J＝7.6Hz,1H), 7.29-7.26(m,2H),7.05(t,J＝8.8Hz,2H),5.76(s,1H),2.66(s,3H)；¹³C NMR(100MHz,CDCl₃) δ159.30(d,J＝241.9Hz),145.15(d,J＝2.4Hz),136.47,134.42,132.99,129.95,129.41,122.16 (d,J＝8.2Hz),116.84,116.07(d,J＝22.5Hz),114.37,112.62,60.66,35.98；HRMS(ESI)calcd for C₁₆H₁₂FN₃[M+H]⁺266.1088, found 266.1093; melting range: 92-93 ℃.

7. Starting from N- (4-chlorophenyl) -N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (reaction scheme 7)

N- (4-chlorophenyl) -N-methylamino-malononitrile (100mg, 0.49 mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (218mg, 0.73mmol), and potassium fluoride (85mg, 1.46mmol) were added in this order to stirred ethanol (2mL) in a 10mL reaction tube under an argon atmosphere, reacted at 10 ℃ for 2 hours to complete the reaction, the solvent was drained on a rotary evaporator, and column chromatography gave a white solid (75mg, 55% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.82(t,J＝7.2Hz,2H),7.72(t,J＝7.6Hz,1H),7.58(t,J＝7.2Hz, 1H),7.31(d,J＝8.8Hz,2H),7.18(d,J＝8.8Hz,2H),5.87(s,1H),2.67(s,3H)；¹³C NMR(100 MHz,CDCl₃)δ147.28,136.33,134.49,133.05,130.00,129.40,129.34,128.31,120.45,116.67, 114.29,112.47,59.26,35.33；HRMS(ESI)calcd for C₁₆H₁₂ ³⁵ClN₃[M+H]⁺:282.0793,found 282.0802；HRMS(ESI)calcd for C₁₆H₁₂ ³⁷ClN₃[M+H]⁺284.0763, found 284.0771, melting range: 108-109 ℃.

8. Starting from N- (2-chlorophenyl) -N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (reaction scheme 8)

N- (2-chlorophenyl) -N-methylamino-malononitrile (10mg, 0.049 mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (29mg, 0.097mmol), and cesium fluoride (15mg, 0.097mmol) were added in this order to stirred 1, 2-dichloroethane (1mL) under an argon atmosphere in a 10mL reaction tube, reacted at 60 ℃ for 1 hour to complete the reaction, the solvent was removed on a rotary evaporator, and column chromatography was performed to obtain a white solid (10mg, 71% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.76-7.73(m,2H),7.65(t,J＝7.6Hz,1H),7.52(t,J＝7.6Hz,1H), 7.45-7.37(m,2H),7.29(t,J＝7.6Hz,1H),7.12(t,J＝7.6Hz,1H),5.73(s,1H),2.83(s,3H)；¹³C NMR(100MHz,CDCl₃)δ145.75,136.09,134.04,132.72,130.93,130.82,129.70,129.03,127.72, 126.58,123.68,116.29,115.79,113.03,58.19,38.46；HRMS(ESI)calcd for C₁₆H₁₂ ³⁵ClN₃[M+H]⁺: 282.0793,found 282.0799；HRMS(ESI)calcd for C₁₆H₁₂ ³⁷ClN₃[M+H]⁺284.0763, found 284.0768, melting range: 79 to 80 ℃.

9. Starting from N- (4-bromophenyl) -N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (reaction scheme 9)

N- (4-bromophenyl) -N-methylamino-malononitrile (300mg, 1.20 mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (430mg, 1.44mmol), cesium fluoride (401mg, 2.64mmol) and 18-crown-6 (698mg, 2.64mmol) were added in this order to stirred N, N-dimethylformamide (2mL) under an argon atmosphere in a 10mL reaction tube, reacted at 70 ℃ for 2 hours to complete the reaction, extracted 3 times with ethyl acetate (10mL) and dried, the resulting organic phase was filtered and the solvent was pumped off on a rotary evaporator, and a white solid (235mg, 60% yield) was obtained by column chromatography.

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.82(t,J＝8.8Hz,2H),7.72(t,J＝7.6Hz,1H),7.57(t,J＝7.2Hz, 1H),7.45(d,J＝8.8Hz,2H),7.11(d,J＝8.8Hz,2H),5.88(s,1H),2.67(s,3H)；¹³C NMR(100 MHz,CDCl₃)δ147.70,136.29,134.49,133.05,132.31,130.00,129.31,120.59,116.63,115.73, 114.26,112.42,58.94,35.22；HRMS(ESI)calcd for C₁₆H₁₂ ⁷⁹BrN₃[M+H]⁺:326.0287,found 326.0298,HRMS(ESI)calcd for C₁₆H₁₂ ⁸¹BrN₃[M+H]⁺328.0267, found 328.0276, melting range: 90-91 ℃.

10. 2- (3, 4-dihydroquinolin-1 (2H) -yl) malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate as raw materials (reaction formula 10)

2- (3, 4-dihydroquinolin-1 (2H) -yl) malononitrile (5g, 25.35mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (7.563g, 25.35mmol), potassium fluoride (2.209g, 38.02mmol) and 18-crown-6 (10.049g, 38.02mmol) were added in succession to a stirred 1, 4-dioxane (15mL) under argon, the reaction was completed at 50 ℃ for 4 hours, extracted 3 times with ethyl acetate (30mL) and dried, the organic phase obtained by filtration was freed from the solvent on a rotary evaporator and chromatographed to give a white solid (3.811g, 55% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.94(d,J＝8.0Hz,1H),7.78(d,J＝7.6Hz,1H),7.73(t,J＝7.6Hz, 1H),7.55(t,J＝7.2Hz,1H),7.15(t,J＝7.2Hz,1H),7.07(d,J＝7.2Hz,1H),6.98(d,J＝8.4Hz, 1H),6.84(t,J＝7.2Hz,1H),6.14(s,1H),3.20-3.14(m,1H),2.95-2.81(m,2H),2.78-2.71(m,1H), 2.06-1.89(m,2H)；¹³C NMR(100MHz,CDCl₃)δ142.96,137.03,134.61,132.98,129.74,129.63, 129.22,127.14,126.29,120.22,116.36,115.21,113.28,112.19,54.96,45.78,27.45,21.98；HRMS (ESI)calcd for C₁₈H₁₅N₃[M+H]⁺274.1339, found 274.1348, melting range: 177 ℃ to 179 ℃.

11. 2- (3, 4-dihydroisoquinoline-2 (1H) -yl) malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate are used as raw materials (reaction formula 11)

2- (3, 4-dihydroisoquinolin-2 (1H) -yl) malononitrile (300mg, 1.52 mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (907mg, 3.04mmol) and tetrabutylammonium fluoride (1192mg, 4.56mmol) were sequentially added to a stirred mixed solvent of tetrahydrofuran: dichloromethane: 1, 2-dichloroethane ═ 1:1:1(6mL) under argon protection, reacted at 15 ℃ for 3 hours to complete the reaction, the solvent was dried on a rotary evaporator, and column chromatography was performed to obtain a white solid (333mg, 80% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.84(d,J＝7.6Hz,1H),7.77-7.69(m,2H),7.54(t,J＝7.2Hz,1H), 7.16-7.09(m,3H),6.97(d,J＝8.0Hz,1H),5.29(s,1H),3.91(d,J＝14.4Hz,1H),3.63(d,J＝ 14.4Hz,1H),3.11-3.00(m,2H),2.92-2.81(m,2H)；¹³C NMR(100MHz,CDCl₃)δ136.78,134.09, 133.51,132.88,132.61,129.62,128.71,128.65,126.44,126.38,125.79,116.46,113.88,113.35, 60.77,51.34,48.09,29.02；HRMS(ESI)calcd for C₁₈H₁₅N₃[M+H]⁺274.1339, found 274.1348, melting range: 110-112 ℃.

12. Using N-butyl-N-phenylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate as raw materials (reaction formula 12)

N-butyl-N-phenylamino-malononitrile (2g, 9.38mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (3.076g, 10.31mmol), cesium fluoride (4.273g, 28.13mmol) were added in succession to a stirred mixed solvent of toluene N, N-dimethylformamide: 1, 2-dichloroethane: 1, 4-dioxane ═ 1:1:1:2(10mL) under argon protection, reacted at 70 ℃ for 1.5 hours to complete the reaction, extracted 3 times with ethyl acetate (20mL) and dried, the organic phase obtained by filtration was freed from the solvent on a rotary evaporator and subjected to column chromatography to give a white solid (1.764g, 65% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.79(d,J＝7.6Hz,1H),7.71(d,J＝7.6Hz,1H),7.63(t,J＝7.6Hz, 1H),7.52(t,J＝7.6Hz,1H),7.32(t,J＝8.4Hz,2H),7.24(d,J＝7.6Hz,2H),7.10(t,J＝7.2Hz, 1H),5.70(s,1H),3.30-3.23(m,1H),2.99-2.91(m,1H),1.47-1.31(m,2H),1.28-1.11(m,2H),0.73 (t,J＝7.6Hz,3H)；¹³C NMR(100MHz,CDCl₃)δ146.58,137.19,134.31,132.77,129.63,129.51, 129.27,124.33,122.56,116.88,115.62,112.80,59.62,49.14,29.23,19.91,13.54；HRMS(ESI) calcd for C₁₉H₁₉N₃[M+H]⁺290.1652, found 290.1659, melting range: 65-66 ℃.

13. Using N-benzyl-N-phenylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate as raw materials (reaction formula 13)

N-benzyl-N-phenylamino-malononitrile (50mg, 0.20mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (90mg, 0.30mmol), cesium fluoride (77mg, 0.51mmol) and 18-crown-6 (135mg, 0.51mmol) were added in succession to a stirred mixed solvent of acetonitrile, tetrahydrofuran ═ 1:4(2.5mL) under argon protection, reacted at 35 ℃ for 2 hours to complete the reaction, the solvent was drained on a rotary evaporator and column chromatography gave a white solid (40.5mg, 62% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.70(t,J＝8.0Hz,2H),7.54(t,J＝7.6Hz,1H),7.41(t,J＝7.2Hz, 1H),7.25-7.22(m,6H),7.18(t,J＝7.2Hz,2H),7.11(t,J＝7.2Hz,1H),7.04-6.99(m,1H),5.86(s, 1H),4.44(d,J＝14.8Hz,1H),4.23(d,J＝14.8Hz,1H)；¹³C NMR(100MHz,CDCl₃)δ146.75, 136.60,136.45,134.25,132.77,129.67,129.62,129.15,128.27,127.93,127.17,124.10,121.91, 116.91,115.19,112.65,58.98,53.82；HRMS(ESI)calcd for C₂₂H₁₇N₃[M+H]⁺324.1495, found 324.1504, melting range: 117-118 ℃.

14. Using N-benzyl-N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate as raw materials (reaction formula 14)

N-benzyl-N-methylamino-malononitrile (100mg, 0.54mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (322mg, 1.08mmol), potassium fluoride (78mg, 1.35mmol) and 18-crown-6 (357mg, 1.35mmol) were added in succession to a stirred mixed solvent of dichloromethane: diethyl ether: ethanol ═ 1:3:1(2mL) under argon protection, reacted at 0 ℃ for 2.5 hours to complete the reaction, the solvent was drained on a rotary evaporator and a white solid (92mg, 65% yield) was obtained by column chromatography.

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.79(d,J＝8.0Hz,2H),7.65(t,J＝7.6Hz,1H),7.51(t,J＝7.6Hz, 1H),7.40(d,J＝6.8Hz,2H),7.32(t,J＝7.2Hz,2H),7.27(t,J＝6.8Hz,1H),5.23(s,1H),3.75(d, J＝12.8Hz,1H),3.66(d,J＝12.8Hz,1H),2.17(s,3H)；¹³C NMR(100MHz,CDCl₃)δ137.12, 136.59,134.20,132.51,129.41,128.98,128.82,128.33,127.57,116.76,113.66,112.89,60.44, 59.14,37.30；HRMS(ESI)calcd for C₁₇H₁₅N₃[M+H]⁺262.1339, found 262.1342, melting range: 82-84 ℃.

15. Using N- (4-fluorobenzyl) -N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate as raw materials (reaction formula 15)

N- (4-fluorobenzyl) -N-methylamino-malononitrile (500mg, 2.46 mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (955mg, 3.20mmol), potassium fluoride (314mg, 5.41mmol) and 18-crown-6 (1430mg, 5.41mmol) were added in this order to a stirred mixed solvent of tetrahydrofuran: 1, 2-dichloroethane ═ 1:3(5mL) under argon protection, reacted at 10 ℃ for 4 hours to complete the reaction, the solvent was drained on a rotary evaporator, and column chromatography was performed to give a yellow oily liquid (481mg, 70% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.78(d,J＝8.4Hz,2H),7.66(t,J＝7.6Hz,1H),7.51(t,J＝7.6Hz, 1H),7.37(t,J＝8.4Hz,2H),7.00(t,J＝8.4Hz,2H),5.22(s,1H),3.74(d,J＝12.8Hz,1H),3.63 (d,J＝12.8Hz,1H),2.13(s,3H)；¹³C NMR(100MHz,CDCl₃)δ162.27(d,J＝244.4Hz),137.11, 134.28,132.62,132.38(d,J＝2.9Hz),130.69(d,J＝8.2Hz),129.53,128.90,116.83,115.24(d,J ＝21.2Hz),113.60,112.93,60.42,58.65,37.11；HRMS(ESI)calcd for C₁₇H₁₄FN₃[M+H]⁺: 280.1245,found 280.1251。

16. using N- (4-chlorobenzyl) -N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonic acid ester as raw materials (reaction formula 16)

N- (4-chlorobenzyl) -N-methylamino-malononitrile (400mg, 1.82) was charged under argon in a 25mL reaction flask

mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (979mg, 3.28mmol), cesium fluoride (719mg, 4.73mmol) and 18-crown-6 (1250mg, 4.73mmol) were added in this order to a stirred mixed solvent of toluene: 1, 2-dichloroethane: 1, 4-dioxane: dichloromethane: tetrahydrofuran ═ 1:3:1:2:5(4.8mL), the reaction was completed at 55 ℃ for 1.5 hours, the solvent was drained on a rotary evaporator, and a yellow solid (377mg, 70% yield) was obtained by column chromatography.

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.80-7.77(m,2H),7.66(t,J＝7.6Hz,1H),7.52(t,J＝7.6Hz,1H), 7.36-7.27(m,4H),5.23(s,1H),3.74(d,J＝12.8Hz,1H),3.62(d,J＝12.8Hz,1H),2.14(s,3H)；¹³C NMR(100MHz,CDCl₃)δ137.02,135.19,134.28,133.40,132.63,130.36,129.56,128.88, 128.55,116.82,113.56,112.92,60.51,58.61 37.23；HRMS(ESI)calcd for C₁₇H₁₄ ³⁵ClN₃[M+H]⁺: 296.0949,found 296.0959；HRMS(ESI)calcd for C₁₇H₁₄ ³⁷ClN₃[M+H]⁺298.0920, found 298.0925, melting range: 101-103 ℃.

17. Starting from N- (4-methylbenzyl) -N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (reaction scheme 17)

N- (4-methylbenzyl) -N-methylamino-malononitrile (5g, 25.09 mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonic acid ester (11.230g, 37.64mmol), tetrabutylammonium fluoride (13.123g, 50.19mmol) were added in succession to a stirred mixed solvent of acetonitrile: N, N-dimethylformamide ═ 4:1(50mL) under argon protection, the reaction was completed at 60 ℃ for 3 hours, extracted 3 times with ethyl acetate (60mL) and dried, the resulting organic phase was filtered, the solvent was drained on a rotary evaporator, and column chromatography was carried out to give a yellow solid (4.906g, 71% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.78(d,J＝7.6Hz,2H),7.65(t,J＝7.6Hz,1H),7.51(t,J＝7.6Hz, 1H),7.30(d,J＝8.0Hz,2H),7.14(d,J＝8.0Hz,2H),5.22(s,1H),3.72(d,J＝12.8Hz,1H),3.65 (d,J＝12.8Hz,1H),2.33(s,3H),2.16(s,3H)；¹³C NMR(100MHz,CDCl₃)δ137.32,134.27, 133.56,132.52,129.41,129.08,129.07,128.93,116.79,113.73,113.04,60.42,59.05,37.30,21.03； HRMS(ESI)calcd for C₁₈H₁₇N₃[M+H]⁺276.1495, found 276.1502, melting range: 112-113 ℃.

18. Using N- (4-methoxybenzyl) -N-methylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonic acid ester as raw materials (reaction formula 18)

N- (4-methoxybenzyl) -N-methylamino-malononitrile (10mg, 0.046 mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonic acid ester (21mg, 0.070mmol), tetrabutylammonium fluoride (37mg, 0.14 mmol) were added in this order to a stirred mixed solvent of dichloromethane: tetrahydrofuran: diethyl ether: 1:4:1(1.2mL) under argon protection, the reaction was completed at 15 ℃ for 1 hour, the solvent was drained on a rotary evaporator, and column chromatography gave a yellow solid (10mg, 72% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.77(d,J＝8.0Hz,2H),7.64(t,J＝7.6Hz,1H),7.50(t,J＝7.6Hz, 1H),7.33(d,J＝8.8Hz,2H),6.86(d,J＝8.8Hz,2H),5.21(s,1H),3.78(s,3H),3.70(d,J＝12.8 Hz,1H),3.62(d,J＝12.8Hz,1H),2.13(s,3H)；¹³C NMR(100MHz,CDCl₃)δ159.15,137.33, 134.30,132.56,130.37,129.42,128.93,128.65,116.86,113.78,113.73,112.96,60.31,58.89,55.16, 37.09；HRMS(ESI)calcd for C₁₈H₁₇N₃O[M+H]⁺292.1444, found 292.1453, melting range: 91-93 ℃.

19. Using N, N-dimethylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate as raw materials (reaction formula 19)

N, N-dimethylamino-malononitrile (100mg, 0.92mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (274mg, 0.92mmol), cesium fluoride (208mg, 1.37mmol) and 18-crown-6 (362mg, 1.37mmol) were added in this order to a stirred mixed solvent of toluene: 1, 2-dichloroethane: diethyl ether ═ 1:1:1(2.4mL) under an argon atmosphere in a 10mL reaction tube, reacted at 25 ℃ for 2.5 hours to complete the reaction, the solvent was evacuated on a rotary evaporator, and column chromatography was performed to obtain a yellow oily liquid (47.5mg, 28% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.74(d,J＝8.0Hz,1H),7.71(d,J＝8.0Hz,1H),7.65(t,J＝8.0Hz, 1H),7.50(t,J＝8.0Hz,1H),5.06(s,1H),2.33(s,6H)；¹³C NMR(100MHz,CDCl₃)δ137.31, 133.93,132.56,129.44,128.51,116.53,113.52,113.09,61.38,41.49；HRMS(ESI)calcd for C₁₁H₁₁N₃[M+H]⁺:186.1026,found 186.1023。

20. 2- (piperidin-1-yl) malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate as raw materials (reaction formula 20)

2- (piperidin-1-yl) malononitrile (100mg, 0.67mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (319mg, 1.07mmol), potassium fluoride (78mg, 1.34mmol) and 18-crown-6 (354mg, 1.34mmol) were added in this order to a stirred 1, 4-dioxane (2mL) under an argon atmosphere, reacted at 70 ℃ for 2.5 hours to complete the reaction, extracted 3 times with ethyl acetate (8mL) and dried, the resulting organic phase was filtered, the solvent was pumped off on a rotary evaporator, and a yellow solid (68mg, 45% yield) was purified by column chromatography.

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.72(d,J＝8.0Hz,1H),7.69(d,J＝8.0Hz,1H),7.62(t,J＝8.0Hz, 1H),7.48(t,J＝8.0Hz,1H),5.00(s,1H),2.60-2.57(m,2H),2.46-2.40(m,2H),1.65-1.57(m,2H), 1.55-1.40(m,4H)；¹³C NMR(100MHz,CDCl₃)δ137.27,133.96,132.26,129.17,128.52,116.47, 113.88,113.02,61.34,50.59,25.30,23.61；HRMS(ESI)calcd for C₁₄H₁₅N₃[M+H]⁺226.1339, found 226.1335, melting range: 65-67 ℃.

21. Starting from morpholinylamino-malononitrile and 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (reaction formula 21)

Morpholinoamino-malononitrile (100mg, 0.64mmol), 2- (trimethylsilyl) phenyltrifluoromethanesulfonate (285mg, 0.96mmol), cesium fluoride (192mg, 1.27mmol) and 18-crown-6 (336mg, 1.27mmol) were added in succession to stirred tetrahydrofuran (2mL) under argon protection in a 10mL reaction tube, reacted at 30 ℃ for 2 hours to complete the reaction, the solvent was drained on a rotary evaporator and column chromatography gave a pale yellow oil (93mg, 64% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.74(d,J＝8.0Hz,1H),7.69(d,J＝8.0Hz,1H),7.63(t,J＝8.0Hz, 1H),7.50(t,J＝8.0Hz,1H),5.03(s,1H),3.71-3.66(m,2H),3.64-3.59(m,2H),2.67-2.62(m,2H), 2.49-2.45(m,2H)；¹³C NMR(100MHz,CDCl₃)δ136.13,133.99,132.45,129.50,128.60,116.35, 113.44,112.97,66.10,60.62,49.47；HRMS(ESI)calcd for C₁₃H₁₃N₃O[M+H]⁺:228.1131,found 228.1128.

22. starting from indolinylamino-malononitrile and 2-methyl-6- (trimethylsilyl) phenyltriflate (equation 22)

Indolinylamino-malononitrile (1.5g, 8.82mmol), 2-methyl-6- (trimethylsilyl) phenyltriflate (2.755g, 8.82mmol), tetrabutylammonium fluoride (3.211g, 12.28 mmol) were added in this order to a stirred mixed solvent of tetrahydrofuran: dichloromethane ═ 1:1(2mL) under argon protection, reacted at 20 ℃ for 2 hours, the solvent was drained on a rotary evaporator, and column chromatography gave a white solid (559mg, 25% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.65(d,J＝7.6Hz,1H),7.53(d,J＝6.8Hz,1H),7.45(t,J＝7.6Hz, 1H),7.17-7.10(m,2H),6.86(t,J＝7.6Hz,1H),6.64(d,J＝7.6Hz,1H),5.80(s,1H),3.51-3.41 (m,2H),3.07-2.94(m,2H),2.66(s,3H)；¹³C NMR(100MHz,CDCl₃)δ149.08,139.23,136.30, 133.89,132.52,130.56,129.78,127.61,124.99,120.78,117.04,115.25,113.48,108.33,51.98, 51.04,28.21,19.97；HRMS(ESI)calcd for C₁₈H₁₅N₃[M+H]⁺274.1339, found 274.1347, melting range: 189-191 ℃.

23. Starting from indolinylamino-malononitrile and 2-methyl-6- (trimethylsilyl) phenyltriflate (equation 23)

Indolinylamino-malononitrile (100mg, 0.55mmol), 2-methyl-6- (trimethylsilyl) phenyltriflate (256mg, 0.82mmol), potassium fluoride (63mg, 1.09mmol) and 18-crown-6 (288mg, 1.09mmol) were added in succession to a stirred mixed solvent of toluene: N, N-dimethylformamide: 1, 4-dioxane ═ 8:1:1(2mL) under argon protection, reacted at 55 ℃ for 2 hours to complete the reaction, extracted 3 times with ethyl acetate (8mL) and dried, the organic phase obtained was filtered off on a rotary evaporator and column chromatographed to give a white solid (79mg, 53% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.72(d,J＝7.6Hz,1H),7.59(t,J＝7.6Hz,1H),7.42(t,J＝8.0Hz, 1H),7.18-7.14(m,2H),6.86(t,J＝7.2Hz,1H),6.80(d,J＝7.6Hz,1H),5.95(s,1H),3.44-3.37 (m,1H),3.17-3.12(m,1H),3.08-3.01(m,1H),2.99-2.91(m,1H),2.61(s,3H)；¹³C NMR(100 MHz,CDCl₃)δ148.42,144.18,136.69,132.40,131.10,130.42,127.56,125.86,124.96,120.97, 115.41,114.58,112.95,108.93,53.70,50.43,28.04,20.79；HRMS(ESI)calcd for C₁₈H₁₅N₃ [M+H]⁺274.1339, found 274.1347, melting range: 117-119 ℃.

24. Starting from indolinylamino-malononitrile and 4-methoxy-2- (trimethylsilyl) phenyltriflate (equation 24)

Indolinylamino-malononitrile (200mg, 1.09mmol), 4-methoxy-2- (trimethylsilyl) phenyltriflate (539mg, 1.64mmol), cesium fluoride (497mg, 3.27 mmol) were added in this order to a stirred mixed solvent of acetonitrile tetrahydrofuran 1:1(2mL) under argon protection, reacted at 15 ℃ for 1 hour, the solvent was drained on a rotary evaporator, and column chromatography gave a white solid (73mg, 23% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.71(d,J＝8.8Hz,1H),7.39(d,J＝2.4Hz,1H),7.18-7.14(m,2H), 7.00(d,J＝8.4Hz,1H),6.86(t,J＝7.6Hz,1H),6.77(d,J＝8.0Hz,1H),5.92(s,1H),3.93(s,3H), 3.43-3.36(m,1H),3.21-3.16(m,1H),3.09-2.92(m,2H)；¹³C NMR(100MHz,CDCl₃)δ162.91, 148.31,138.50,135.94,130.39,127.56,124.99,121.00,116.66,115.32,114.39,114.32,108.86, 103.93,55.89,53.54,50.42,28.05；HRMS(ESI)calcd for C₁₈H₁₅N₃O[M+H]⁺290.1288, found 290.1299, melting range: 168-169 ℃.

25. Starting from indolinylamino-malononitrile and 4-methoxy-2- (trimethylsilyl) phenyltriflate (equation 25)

Indolinylamino-malononitrile (200mg, 1.09mmol), 4-methoxy-2- (trimethylsilyl) phenyltriflate (539mg, 1.64mmol), cesium fluoride (497mg, 3.27 mmol) were added in this order to a stirred mixed solvent of acetonitrile tetrahydrofuran 1:1(2mL) under argon protection, reacted at 15 ℃ for 1 hour, the solvent was drained on a rotary evaporator, and column chromatography gave a white solid (148mg, 47% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.77(d,J＝8.4Hz,1H),7.26(d,J＝2.8Hz,1H),7.20-7.13(m,3H), 6.85(t,J＝7.6Hz,1H),6.76(d,J＝8.4Hz,1H),5.90(s,1H),3.86(s,3H),3.40-3.33(m,1H), 3.16-3.11(m,1H),3.07-2.89(m,2H)；¹³C NMR(100MHz,CDCl₃)δ160.03,148.36,130.43, 129.92,128.18,127.51,124.95,120.89,119.43,118.39,116.14,114.66,113.56,108.83,55.80, 52.80,50.25,27.99；HRMS(ESI)calcd for C₁₈H₁₅N₃O[M+H]⁺290.1288, found 290.1299, melting range: 134-136 ℃.

26. Starting from indolinylamino-malononitrile and 4, 5-dimethoxy-2- (trimethylsilyl) phenyltriflate (equation 26)

Indolylamino-malononitrile (20mg, 0.109mmol), 4, 5-dimethoxy-2- (trimethylsilyl) phenyltriflate (59mg, 0.164mmol), cesium fluoride (50mg, 0.327mmol) and 18-crown-6 (86mg, 0.327mmol) were added in succession to stirred diethyl ether (1mL) under argon protection in a 10mL reaction tube, reacted at 0 ℃ for 4 hours, the solvent was drained on a rotary evaporator and the column chromatography gave a white solid (22mg, 64% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.27(s,1H),7.17-7.13(m,3H),6.85(t,J＝7.2Hz,1H),6.76(d,J＝ 8.0Hz,1H),5.91(s,1H),4.00(s,3H),3.91(s,3H),3.41-3.34(m,1H),3.21-3.16(m,1H), 3.08-2.91(m,2H)；¹³C NMR(100MHz,CDCl₃)δ152.50,149.39,148.30,130.38,130.32,127.49, 124.92,120.87,116.58,115.45,114.76,111.09,108.78,103.91,56.38,56.31,53.15,50.36,27.99； HRMS(ESI)calcd for C₁₉H₁₇N₃ O₂[M+H]⁺320.1394, found 320.1404, melting range: 183-185 ℃.

27. Starting from indolinylamino-malononitrile and 3- (trimethylsilyl) -2-naphthyltrifluoromethanesulfonate (equation 27)

Indolinylamino-malononitrile (500mg, 2.73mmol), 3- (trimethylsilyl) -2-naphthyltrifluoromethanesulfonate (1902mg, 5.46mmol), potassium fluoride (476mg, 8.19mmol) and 18-crown-6 (2159mg, 8.169mmol) were added in this order to a stirred mixed solvent of ethanol 1, 2-dichloroethane 1:1(6mL) under argon atmosphere, reacted at 45 ℃ for 1.5 hours to complete the reaction, the solvent was drained on a rotary evaporator and column chromatography gave a white solid (599mg, 71% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ8.34(d,J＝12.0Hz,2H),8.01(d,J＝8.0Hz,1H),7.95(d,J＝8.0 Hz,1H),7.78-7.69(m,2H),7.19-7.15(m,2H),6.89-6.83(m,2H),6.08(s,1H),3.48-3.41(m,1H), 3.16-3.11(m,1H),3.08-3.02(m,1H),3.00-2.91(m,1H)；¹³C NMR(100MHz,CDCl₃)δ148.41, 136.66,133.93,132.14,130.57,130.47,130.13,128.81,128.52,128.43,128.29,127.62,125.06, 121.10,116.78,114.65,109.30,109.03,53.77,50.36,28.05；HRMS(ESI)calcd for C₂₁H₁₅N₃ [M+H]⁺310.1339, found 310.1349, melting range: 241-242 ℃.

28. Starting from indolinylamino-malononitrile and 6- (trimethylsilyl) -2, 3-dihydro-1H-indan-trifluoromethanesulfonate (equation 28)

Indolylamino-malononitrile (100mg, 0.55mmol), 6- (trimethylsilyl) -2, 3-dihydro-1H-indane-trifluoromethanesulfonate (277mg, 0.82mmol), cesium fluoride (165mg, 1.09mmol) and 18-crown-6 (289mg, 1.09mmol) were added in succession to stirred tetrahydrofuran (2mL) under argon protection, reacted at 30 ℃ for 2 hours to complete the reaction, the solvent was dried on a rotary evaporator and column chromatographed to give a pale yellow solid (124mg, 76% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.74(s,1H),7.59(s,1H),7.16(t,J＝8.0Hz,2H),6.87-6.81(m, 2H),5.97(s,1H),3.43-3.36(m,1H),3.20-3.14(m,1H),3.08-2.90(m,6H),2.21-2.14(m,2H)；¹³C NMR(100MHz,CDCl₃)δ150.62,148.36,146.28,134.34,130.26,129.59,127.36,124.76,124.56, 120.65,116.90,114.68,109.93,108.69,53.20,50.12,33.10,32.17,27.86,24.94；HRMS(ESI) calcd for C₂₀H₁₇N₃[M+H]⁺300.1495, found 300.1491; melting range: 156-158 ℃.

29. Starting from indolinylamino-malononitrile and 6- (trimethylsilyl) benzo [ d ] [1,3] dioxo-5-methyltrifluoromethanesulfonate (reaction scheme 29)

Indolylamino-malononitrile (10g, 54.58mmol), 6- (trimethylsilyl) benzo [ d ] [1,3] dioxo-5-methyltrifluoromethane sulfonate (18.686g, 54.58mmol), tetrabutylammonium fluoride (21.406g, 81.87mmol) were added in succession to stirred dichloromethane (60mL) under argon protection in a 300mL reaction flask, the reaction was completed at 10 ℃ for 1 hour, the solvent was drained on a rotary evaporator and the column chromatography gave a yellow solid (11.589g, 70% yield).

The product detection data were as follows:

¹H NMR(400MHz,CDCl₃)δ7.32(s,1H),7.18-7.12(m,3H),6.86(t,J＝8.0Hz,1H),6.78(d,J＝ 8.0Hz,1H),6.13(s,2H),5.90(s,1H),3.42-3.35(m,1H),3.25-3.19(m,1H),3.09-2.91(m,2H)；¹³C NMR(100MHz,CDCl₃)δ151.66,148.39,148.25,132.67,130.29,127.49,124.92,120.90, 116.29,114.53,112.68,109.19,108.77,105.30,103.06,53.10,50.31,27.98；HRMS(ESI)calcd for C₁₈H₁₃N₃O₂[M+H]⁺304.1081, found 304.1077, melting range: 169 ℃ to 171 ℃.