1,2,4-triazole and preparation method therefor

Abstract

A method for preparing 1,2,4-triazole includes using a fluoroborate aryl diazonium salt, a diazoester derivative and an organic nitrile as reaction substrates, a transition metal salt as a catalyst, and an inorganic base as an additive in a cyclization reaction. The method has the following characteristics: the reaction is economical; the substrate is universal; the post-functionalization is easy; the reaction conditions are mild; the reaction can be performed in air; the catalyst amount used is less; and the post-treatment is simple. Meanwhile, the raw materials, such as the reactants and the catalyst used, are inexpensive and easily available; the reaction composition is reasonable; no ligand is needed; there are less reaction steps; and only one step of reaction is required to obtain a high yield, meeting the requirements and directions of contemporary green chemistry and medicinal chemistry, being suitable for screening highly active 1,2,4-triazole drugs.

Claims

1. A method of preparing a 1,2,4-triazole, comprising: conducting a cyclization reaction of a fluoroborate aryl diazonium salt, a diazonium ester derivative and an organic nitrile, in the presence of a copper salt as a catalyst and an inorganic base as an additive, to obtain the 1,2,4-triazole, wherein the fluoroborate aryl diazonium salt has the following chemical structural formula: ##STR00040##  and Ar is selected from the group consisting of an aryl group, a monosubstituted aryl group, a disubstituted aryl group, and naphthyl; wherein the diazonium ester derivative has the following chemical formula: ##STR00041##  and R.sup.1 is selected from the group consisting of ethyl, isopropyl, tert-butyl, cyclohexyl, phenyl, benzyl, ##STR00042##  —CH.sub.2CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CF.sub.3, —CH.sub.2CH.sub.2Br, ##STR00043##  and —CH.sub.2CH.sub.2CH═CH.sub.2; wherein the organic nitrile has the following chemical structural formula: R.sup.2—C≡N, and R.sup.2 is selected form the group consisting of methyl, isopropyl, tert-butyl, benzyl, —CH.sub.2CH.sub.2CH.sub.2Cl, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH═CH.sub.2, —CH═CHCH.sub.3, and ##STR00044## wherein the 1,2,4-triazole has the following chemical structural formula: ##STR00045##

2. The method according to claim 1, wherein the cyclization reaction is conducted at 40° C. for 1 hour in the air.

3. The method according to claim 1, wherein the copper salt was a halogen copper salt, and the additive is selected from the group consisting of lithium carbonate, potassium carbonate, cesium carbonate, sodium acetate, and lithium tert-butoxide.

4. The method according to claim 3, wherein the copper salt is cuprous bromide, and the additive is lithium carbonate.

5. The method according to claim 1, wherein the aryl group is phenyl; the monosubstituted aryl group has the following chemical structural formula: ##STR00046## and R is selected from the group consisting of hydrogen, methyl, isopropyl, tert-butyl, isopropyl, methoxy, fluoride, chlorine, bromine, trifluoromethyl, and trifluoromethoxy; and the disubstituted aryl group is selected from the group consisting of ##STR00047##

6. The method according to claim 1, wherein a molar ratio of the catalyst to the fluoroborate aryl diazonium salt is 20%; and a molar ratio of the additive to the fluoroborate aryl diazonium salt is 1.

7. The method according to claim 1, wherein a molar ratio of the organic nitrile to the fluoroborate aryl diazonium salt is 20-50; and a molar ratio of the diazonium ester derivative to the fluoroborate aryl diazonium salt is 3.

Description

EMBODIMENTS OF THE INVENTION

(1) The present invention is further described below in conjunction with the embodiments:

(2) The raw materials, catalysts and additives of the invention are all market-oriented commodities, and can be directly purchased or prepared according to conventional techniques. For example, the aryl diazonium fluoroborate can be obtained by reacting a marketed aromatic amine, sodium nitrite and fluoroboric acid; The diazo ester derivative can be synthesized by a commercially available alcohol with a simple starting material such as bromoacetyl bromide, p-toluenesulfonyl hydrazide or p-toluenesulfonyl chloride.

Example 1

(3) ##STR00009##

(4) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4a was obtained by simple column chromatography with a yield of 85%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(5) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.33-7.25 (m, 4H), 4.36 (q, J=8.0 Hz, 2H), 2.51 (s, 3H), 2.43 (s, 3H), 1.34 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.79, 157.28, 144.66, 139.60, 135.29, 129.33, 125.31, 62.38, 21.15, 13.89, 13.72. HRMS (ESI-TOF): Anal. Calcd. For C.sub.13H.sub.15N.sub.3O.sub.2+Na.sup.+: 284.1006, Found: 284.1015; IR (neat, cm.sup.−1): ν 2936.42, 1731.74, 1519.50, 1255.34, 1234.01, 1112.29, 1107.30, 827.78.

Example 2

(6) ##STR00010##

(7) Compound 1b (0.2 mmol, 43.4 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4b was obtained by simple column chromatography with a yield of 71%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(8) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.33-7.25 (m, 4H), 4.36 (q, J=8.0 Hz, 2H), 2.51 (s, 3H), 2.43 (s, 3H), 1.34 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.79, 157.28, 144.66, 139.60, 135.29, 129.33, 125.31, 62.38, 21.15, 13.89, 13.72. HRMS (ESI-TOF): Anal. Calcd. For C.sub.13H.sub.15N.sub.3O.sub.2+H.sup.+: 246.1237, Found: 246.1235; IR (neat, cm.sup.−1): ν 2986.72, 1728.32, 1518.54, 1300.80, 1229.34, 1118.00, 1052.76, 816.07.

Example 3

(9) ##STR00011##

(10) Compound 1c (0.2 mmol, 49.3 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4c was obtained by simple column chromatography with a yield of 70%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(11) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.38-7.30 (m, 4H), 4.36 (q, J=8.0 Hz, 2H), 2.99 (dt, J=13.8, 6.9 Hz, 1H), 2.51 (s, 3H), 1.33 (t, J=8.0 Hz, 3H), 1.28 (d, J=6.9 Hz, 6H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.80, 157.31, 150.40, 144.63, 135.51, 126.77, 125.38, 62.38, 33.82, 23.76, 13.87, 13.72. HRMS (ESI-TOF): Anal. Calcd. For C.sub.15H.sub.19N.sub.3O.sub.2+H.sup.+: 274.1550, Found: 274.1549; IR (neat, cm.sup.−1): ν 2960.85, 1739.54, 1521.23, 1224.84, 1115.14, 1057.49, 853.78, 837.46.

Example 4

(12) ##STR00012##

(13) Compound 1d (0.2 mmol, 52.3 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4d was obtained by simple column chromatography with a yield of 66%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(14) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.52-7.46 (m, 2H), 7.39-7.32 (m, 2H), 4.37 (q, J=8.0 Hz, 2H), 2.51 (s, 3H), 1.38-1.30 (m, 12H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.79, 157.32, 152.65, 144.60, 135.21, 125.70, 125.02, 62.37, 34.73, 31.16, 13.88, 13.73. HRMS (ESI-TOF): Anal. Calcd. For C.sub.16H.sub.21N.sub.3O.sub.2+Na.sup.+: 310.1526, Found: 310.1536; IR (neat, cm.sup.−1): ν 2962.52, 1740.86, 1523.31, 1483.23, 1227.50, 1104.75, 1055.22, 841.35.

Example 5

(15) ##STR00013##

(16) Compound 1e (0.2 mmol, 56.5 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4e was obtained by simple column chromatography with a yield of 52%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(17) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.74-7.67 (m, 2H), 7.62 (m, 2H), 7.54-7.44 (m, 4H), 7.42-7.36 (m, 1H), 4.39 (q, J=8.0 Hz, 2H), 2.53 (s, 3H), 1.36 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 161.07, 157.37, 144.74, 142.48, 139.74, 136.86, 128.85, 127.86, 127.46, 127.16, 125.88, 62.56, 13.97, 13.80. HRMS (ESI-TOF): Anal. Calcd. For C.sub.18H.sub.17N.sub.3O.sub.2+Na.sup.+: 330.1213, Found: 330.1220; IR (neat, cm.sup.−1): ν 2920.13, 1745.02, 1299.15, 1220.32, 1112.49, 1055.96, 770.05, 705.14.

Example 6

(18) ##STR00014##

(19) Compound 1f (0.2 mmol, 40.4 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4f was obtained by simple column chromatography with a yield of 64%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(20) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.51-7.46 (m, 3H), 7.46-7.41 (m, 2H), 4.36 (q, J=8.0 Hz, 2H), 2.52 (s, 3H), 1.32 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.86, 157.15, 144.66, 137.72, 129.38, 128.70, 125.50, 62.36, 13.80, 13.65. HRMS (ESI-TOF): Anal. Calcd. For C.sub.12H.sub.13N.sub.3O.sub.2+Na.sup.+: 254.0900, Found: 254.0903; IR (neat, cm.sup.−1): ν 2986.08, 1734.75, 1509.89, 1227.99, 1118.24, 1053.52, 765.16, 694.81.

Example 7

(21) ##STR00015##

(22) Compound 1g (0.2 mmol, 44.2 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4g was obtained by simple column chromatography with a yield of 60%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(23) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.53-7.32 (m, 2H), 7.23-7.06 (m, 2H), 4.37 (q, J=8.0 Hz, 2H), 2.51 (s, 3H), 1.35 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 164.00, 161.51, 160.99, 157.10, 144.75, 133.82, 133.79, 127.64, 127.55, 115.87, 115.64, 62.52, 13.87, 13.67. HRMS (ESI-TOF): Anal. Calcd. For C.sub.12H.sub.12FN.sub.3O.sub.2+Na.sup.+: 272.0806, Found: 272.0801; IR (neat, cm.sup.−1): ν 2987.77, 1728.00, 1517.03, 1484.20, 1232.15, 1122.99, 1051.12, 834.38.

Example 8

(24) Compound 1h (0.2 mmol, 47.7 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4h was obtained by simple column chromatography with a yield of 54%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(25) ##STR00016##

(26) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.52-7.43 (m, 2H), 7.42-7.34 (m, 2H), 4.38 (q, J=8.0 Hz, 2H), 2.51 (s, 3H), 1.36 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 161.23, 157.20, 144.76, 136.24, 135.48, 129.01, 126.96, 62.66, 13.95, 13.75. HRMS (ESI-TOF): Anal. Calcd. For C.sub.12H.sub.12ClN.sub.3O.sub.2+Na.sup.+: 288.0510, Found: 288.0499; IR (neat, cm.sup.−1): ν 2923.78, 1728.88, 1479.44, 1302.47, 1235.60, 1100.73, 1051.74, 830.37.

Example 9

(27) ##STR00017##

(28) Compound 1i (0.2 mmol, 56.0 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4i was obtained by simple column chromatography with a yield of 53%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(29) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.79-7.51 (m, 2H), 7.40-7.24 (m, 2H), 4.38 (q, J=8.0 Hz, 2H), 2.51 (s, 3H), 1.36 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 161.3, 157.2, 144.7, 136.7, 132.0, 127.2, 123.5, 62.7, 14.0, 13.8. HRMS (ESI-TOF): Anal. Calcd. For C.sub.12H.sub.12BrN.sub.3O.sub.2+Na.sup.+: 332.0005, 333.9985, Found: 332.0006, 333.9983; IR (neat, cm.sup.−1): ν 2977.70, 1728.33, 1497.41, 1301.34, 1235.41, 1122.10, 1099.21, 827.50.

Example 10

(30) ##STR00018##

(31) Compound 1j (0.2 mmol, 58.1 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4j was obtained by simple column chromatography with a yield of 46%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(32) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.58-7.45 (m, 2H), 7.34 (d, J=8.4 Hz, 2H), 4.38 (q, J=8.0 Hz, 2H), 2.52 (s, 3H), 1.35 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 161.31, 157.18, 149.58, 144.83, 136.13, 127.35, 121.15, 62.71, 13.92, 13.76. HRMS (ESI-TOF): Anal. Calcd. For C.sub.13H.sub.12F.sub.3N.sub.3O.sub.3+Na.sup.+: 338.0723, Found: 338.0718; IR (neat, cm.sup.−1): ν 2990.01, 1741.28, 1517.71, 1257.97, 1203.59, 1161.03, 1122.05, 860.53.

Example 11

(33) ##STR00019##

(34) Compound 1k (0.2 mmol, 43.4 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4k was obtained by simple column chromatography with a yield of 69%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(35) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.36 (m, 1H), 7.29 (m, 1H), 7.27-7.19 (m, 1H), 4.36 (q, J=8.0 Hz, 2H), 2.51 (s, 3H), 2.42 (s, 3H), 1.33 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.87, 157.27, 144.73, 139.01, 137.70, 130.24, 128.54, 126.04, 122.66, 62.41, 21.16, 13.89, 13.73. HRMS (ESI-TOF): Anal. Calcd. For C.sub.13H.sub.15N.sub.3O.sub.2+Na.sup.+: 268.1056, Found: 268.1060; IR (neat, cm.sup.−1): ν 2925.21, 1732.17, 1504.01, 1231.72, 1115.47, 1062.54, 796.71, 694.59.

Example 12

(36) ##STR00020##

(37) Compound 1l (0.2 mmol, 47.7 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4l was obtained by simple column chromatography with a yield of 46%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(38) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.67-7.59 (m, 2H), 7.43-7.33 (m, 2H), 4.38 (q, J=8.0 Hz, 2H), 2.51 (s, 3H), 1.35 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 161.30, 157.08, 144.83, 138.72, 132.58, 129.96, 128.85, 124.41, 122.10, 62.67, 13.91, 13.73. HRMS (ESI-TOF): Anal. Calcd. For C.sub.12H.sub.12ClN.sub.3O.sub.2+Na.sup.+: 288.0510, Found: 288.0519; IR (neat, cm.sup.−1): ν 2918.90, 1728.46, 1504.34, 1296.90, 1233.04, 1122.62, 786.51, 682.53.

Example 13

(39) ##STR00021##

(40) Compound 1m (0.2 mmol, 56.0 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4m was obtained by simple column chromatography with a yield of 40%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(41) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.50-7.46 (m, 2H), 7.45-7.40 (m, 1H), 7.37-7.33 (m, 1H), 4.38 (q, J=8.0 Hz, 2H), 2.51 (s, 3H), 1.35 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 161.28, 157.08, 144.82, 138.65, 134.50, 129.76, 129.72, 126.08, 123.97, 62.73, 13.93, 13.74. HRMS (ESI-TOF): Anal. Calcd. For C.sub.12H.sub.12BrN.sub.3O.sub.2+Na.sup.+: 332.0005, 333.9985, Found: 332.0016, 333.9995; IR (neat, cm.sup.−1): ν 2935.73, 1731.12, 1472.25, 1231.83, 1123.08, 867.37, 790.69, 682.99.

Example 14

(42) ##STR00022##

(43) Compound 1n (0.2 mmol, 54.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4n was obtained by simple column chromatography with a yield of 31%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(44) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.80-7.73 (m, 2H), 7.69-7.60 (m, 2H), 4.38 (q, J=8.0 Hz, 2H), 2.53 (s, 3H), 1.34 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 161.48, 157.07, 144.88, 138.17, 131.96, 131.63, 131.30, 130.97, 129.41, 129.04, 126.23, 126.20, 126.16, 126.12, 124.59, 122.96, 122.92, 122.89, 122.85, 121.88, 62.73, 13.84, 13.70. HRMS (ESI-TOF): Anal. Calcd. For C.sub.13H.sub.12F.sub.3N.sub.3O.sub.2+H.sup.+: 300.0954, Found: 300.0955; IR (neat, cm.sup.−1): ν 2957.27, 1735.31, 1329.97, 1282.83, 1187.40, 1167.55, 1121.79, 803.91.

Example 15

(45) ##STR00023##

(46) Compound to (0.2 mmol, 45.0 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4o was obtained by simple column chromatography with a yield of 62%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(47) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.48-7.41 (m, 1H), 7.39 (m, 1H), 7.07 (m, 1H), 7.01 (m, 1H), 4.32 (q, J=8.0 Hz, 2H), 3.75 (s, 3H), 2.51 (s, 3H), 1.29 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.87, 157.18, 153.34, 146.25, 130.74, 127.15, 126.88, 120.57, 111.54, 62.02, 55.53, 13.84, 13.77. HRMS (ESI-TOF): Anal. Calcd. For C.sub.13H.sub.15N.sub.3O.sub.3+Na.sup.+: 284.1006, Found: 284.0993; IR (neat, cm.sup.−1): ν 2919.79, 1731.90, 1494.78, 1290.07, 1248.55, 1100.45, 1038.55, 781.89.

Example 16

(48) ##STR00024##

(49) Compound 1p (0.2 mmol, 50.6 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4p was obtained by simple column chromatography with a yield of 63%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(50) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.39-7.30 (m, 2H), 7.28-7.23 (m, 1H), 4.33 (q, J=8.0 Hz, 2H), 2.56 (s, 3H), 2.08 (s, 3H), 1.28 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 161.96, 156.60, 146.00, 137.50, 135.30, 131.80, 130.53, 129.05, 127.32, 62.43, 17.68, 13.95, 13.82. HRMS (ESI-TOF): Anal. Calcd. For C.sub.13H.sub.14ClN.sub.3O.sub.2+Na.sup.+: 302.0667, Found: 302.0677; IR (neat, cm.sup.−1): ν 2969.18, 1729.02, 1448.87, 1231.15, 1119.39, 1086.66, 1039.00, 800.42.

Example 17

(51) ##STR00025##

(52) Compound 1q (0.2 mmol, 52.9 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4q was obtained by simple column chromatography with a yield of 41%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(53) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.15 (d, J=2.2 Hz, 1H), 7.64 (dd, J=8.2, 2.2 Hz, 1H), 7.49 (d, J=8.3 Hz, 1H), 4.41 (q, J=8.0 Hz, 2H), 2.70 (s, 3H), 2.52 (s, 3H), 1.38 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 161.58, 157.13, 148.59, 144.79, 136.25, 135.09, 133.11, 129.91, 122.26, 62.88, 20.41, 13.94, 13.73. HRMS (ESI-TOF): Anal. Calcd. For C.sub.13H.sub.14N.sub.4O.sub.4+Na.sup.+: 313.0907, Found: 313.0915; IR (neat, cm.sup.−1): ν 2922.97, 1726.18, 1532.44, 1483.18, 1349.06, 1295.79, 1123.24, 1079.32.

Example 18

(54) ##STR00026##

(55) Compound 1r (0.2 mmol, 55.6 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4r was obtained by simple column chromatography with a yield of 39%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(56) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.03 (d, J=2.3 Hz, 1H), 7.48 (dd, J=8.2, 2.4 Hz, 1H), 7.38 (d, J=8.2 Hz, 1H), 4.38 (q, J=8.0 Hz, 2H), 3.90 (s, 3H), 2.69 (s, 3H), 2.52 (s, 3H), 1.35 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.47, 161.15, 157.22, 144.77, 142.09, 135.57, 132.16, 129.86, 128.82, 127.87, 62.59, 52.04, 21.55, 13.93, 13.76. HRMS (ESI-TOF): Anal. Calcd. For C.sub.15H.sub.17N.sub.3O.sub.4+Na.sup.+: 326.1111, Found: 326.1123; IR (neat, cm.sup.−1): ν 2921.53, 1723.83, 1509.26, 1310.41, 1222.22, 1119.70, 1086.25, 781.90.

Example 19

(57) ##STR00027##

(58) Compound is (0.2 mmol, 51.0 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 4s was obtained by simple column chromatography with a yield of 61%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(59) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.91 (m, 4H), 7.62-7.46 (m, 3H), 4.36 (q, J=8.0 Hz, 2H), 2.55 (s, 3H), 1.30 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 161.08, 157.33, 144.95, 135.14, 133.19, 132.66, 128.75, 128.28, 127.80, 127.23, 127.02, 124.43, 123.25, 62.51, 13.92, 13.81. HRMS (ESI-TOF): Anal. Calcd. For C.sub.16H.sub.15N.sub.3O.sub.2+Na.sup.+: 304.1056, Found: 304.1066; IR (neat, cm.sup.−1): ν 2935.17, 1727.51, 1302.74, 1246.98, 1109.87, 1057.21, 811.15, 745.81.

Example 20

(60) ##STR00028##

(61) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2b (0.6 mmol, 78.5 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 5a was obtained by simple column chromatography with a yield of 85%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(62) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.38-7.30 (m, 2H), 7.03-6.93 (m, 2H), 5.19 (dt, J=12.6, 6.3 Hz, 1H), 3.85 (s, 3H), 2.50 (s, 3H), 1.30 (d, J=6.3 Hz, 6H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.60, 160.07, 156.83, 145.08, 130.82, 126.82, 113.76, 70.47, 55.38, 21.37, 13.69. HRMS (ESI-TOF): Anal. Calcd. For C.sub.14H.sub.17N.sub.3O.sub.3+H.sup.+: 276.1343, Found: 276.1355; IR (neat, cm.sup.−1): ν 2984.11, 1722.12, 1518.55, 1303.28, 1244.48, 1126.76, 1102.00, 827.13.

Example 21

(63) ##STR00029##

(64) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2c (0.6 mmol, 87.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 5b was obtained by simple column chromatography with a yield of 46%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(65) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.34-7.29 (m, 2H), 7.01-6.93 (m, 2H), 3.86 (s, 3H), 2.49 (s, 3H), 1.47 (s, 9H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.53, 160.08, 156.43, 146.13, 131.16, 126.79, 113.90, 84.20, 55.49, 27.73, 13.78. HRMS (ESI-TOF): Anal. Calcd. For C.sub.15H.sub.19N.sub.3O.sub.3+H.sup.+: 290.1499, Found: 290.1507; IR (neat, cm.sup.−1): ν 2924.07, 1732.96, 1516.63, 1250.67, 1234.74, 1114.37, 1102.41, 836.77.

Example 22

(66) ##STR00030##

(67) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2d (0.6 mmol, 103.0 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 5c was obtained by simple column chromatography with a yield of 70%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(68) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.38-7.29 (m, 2H), 7.03-6.89 (m, 2H), 5.02-4.86 (m, 1H), 3.86 (s, 3H), 2.56-2.46 (s, 3H), 1.94-1.85 (m, 2H), 1.73-1.62 (m, 2H), 1.58-1.40 (m, 3H), 1.37-1.15 (m, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.68, 160.13, 156.86, 145.26, 130.94, 126.88, 113.85, 75.60, 55.47, 31.18, 24.97, 23.69, 13.76. HRMS (ESI-TOF): Anal. Calcd. For C.sub.17H.sub.21N.sub.3O.sub.3+Na.sup.+: 338.1475, Found: 338.1463; IR (neat, cm.sup.−1): ν 2936.47, 1731.18, 1518.58, 1251.82, 1221.23, 1117.26, 1049.51, 839.39.

Example 23

(69) ##STR00031##

(70) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol) compound 3a (0.5 ml) and compound 2e (0.6 mmol, 99.3 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 5d was obtained by simple column chromatography with a yield of 86%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(71) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.43-7.33 (m, 4H), 7.27-7.21 (m, 1H), 7.18-7.12 (m, 2H), 6.99-6.93 (m, 2H), 3.81 (s, 3H), 2.58 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 161.08, 160.28, 155.79, 149.73, 144.06, 130.50, 129.42, 126.89, 126.42, 121.21, 113.96, 55.46, 13.80. HRMS (ESI-TOF): Anal. Calcd. For C.sub.17H.sub.15N.sub.3O.sub.3+H.sup.+: 310.1186, Found: 310.1177; IR (neat, cm.sup.−1): ν 2823.11, 1741.42, 1302.15, 1250.80, 1232.35, 830.89, 750.85, 725.17.

Example 24

(72) ##STR00032##

(73) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2f (0.6 mmol, 107.9 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 5e was obtained by simple column chromatography with a yield of 72%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(74) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.43-7.16 (m, 7H), 6.99-6.78 (m, 2H), 5.30 (s, 2H), 3.83 (s, 3H), 2.49 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.81, 160.14, 157.10, 144.60, 134.39, 130.66, 128.66, 128.54, 128.45, 126.82, 113.88, 67.81, 55.41, 13.72. HRMS (ESI-TOF): Anal. Calcd. For C.sub.18H.sub.17N.sub.3O.sub.3+H.sup.+: 324.1343, Found: 324.1350; IR (neat, cm.sup.−1): ν 2992.11, 1728.03, 1517.60, 1300.65, 1251.15, 1239.09, 1120.72, 1105.86.

Example 25

(75) ##STR00033##

(76) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2g (0.6 mmol, 147.2 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 5f was obtained by simple column chromatography with a yield of 84%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(77) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.03 (d, J=8.2 Hz, 1H), 7.87-7.82 (m, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.53-7.44 (m, 2H), 7.40-7.34 (m, 1H), 7.30 (d, J=6.4 Hz, 1H), 7.28-7.23 (m, 2H), 6.95-6.87 (m, 2H), 4.68-4.58 (t, J=8.0 Hz, 2H), 3.80 (s, 3H), 3.48 (t, J=8.0 Hz, 2H), 2.52 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.78, 160.12, 157.19, 144.51, 133.73, 132.57, 131.80, 130.60, 128.72, 127.55, 126.97, 126.74, 126.24, 125.64, 125.41, 123.27, 113.84, 65.89, 55.40, 31.88, 13.74. HRMS (ESI-TOF): Anal. Calcd. For C.sub.23H.sub.21N.sub.3O.sub.3+H.sup.+: 388.1656, Found: 388.1645; IR (neat, cm.sup.−1): ν 2964.75, 1732.15, 1517.85, 1253.72, 1214.09, 1115.14, 840.27, 809.79.

Example 26

(78) ##STR00034##

(79) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2h (0.6 mmol, 114.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 5g was obtained by simple column chromatography with a yield of 53%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(80) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.48-7.29 (m, 2H), 7.08-6.89 (m, 2H), 4.47-4.30 (m, 2H), 3.86 (s, 3H), 2.50 (s, 3H), 1.19-0.95 (m, 2H), 0.03 (2, 9H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.71, 160.17, 157.49, 144.87, 130.76, 126.88, 113.89, 64.97, 55.46, 17.38, 13.76, −1.73. HRMS (ESI-TOF): Anal. Calcd. For C.sub.16H.sub.23N.sub.3O.sub.3Si+H.sup.+: 334.1581, Found: 334.1585; IR (neat, cm.sup.−1): ν 2954.63, 1737.78, 1517.88, 1250.59, 1230.20, 1118.37, 866.69, 829.30.

Example 27

(81) ##STR00035##

(82) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2i (0.6 mmol, 96.9 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 5h was obtained by simple column chromatography with a yield of 85%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(83) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.38-7.31 (m, 2H), 7.02-6.94 (m, 2H), 4.38 (t, J=8.0 Hz, 2H), 3.86 (s, 3H), 3.37 (t, J=6.2 Hz, 2H), 3.29 (s, 3H), 2.50 (s, 3H), 1.99-1.91 (m, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.79, 160.21, 157.31, 144.73, 130.78, 126.88, 113.92, 68.67, 63.68, 58.55, 55.48, 28.60, 13.75. HRMS (ESI-TOF): Anal. Calcd. For C.sub.15H.sub.19N.sub.3O.sub.4+Na.sup.+: 328.1268, Found: 328.1266; IR (neat, cm.sup.−1): ν 2926.65, 1736.51, 1518.71, 1252.57, 1217.87, 1116.87, 1050.56, 837.62.

Example 28

(84) ##STR00036##
Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3a (0.5 ml) and compound 2l (0.6 mmol, 120.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 5k was obtained by simple column chromatography with a yield of 74%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(85) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.34-7.28 (m, 2H), 7.15 (m, 1H), 6.94 (m, 3H), 6.83 (d, J=3.4 Hz, 1H), 4.51 (t, J=7.2 Hz, 2H), 3.85 (s, 3H), 3.23 (t, J=7.2 Hz, 2H), 2.51 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.83, 160.18, 157.12, 144.43, 138.58, 130.62, 126.92, 126.79, 125.73, 124.12, 113.90, 66.15, 55.45, 28.86, 13.75. HRMS (ESI-TOF): Anal. Calcd. For C.sub.17H.sub.17N.sub.3O.sub.3S+H.sup.+: 344.1063, Found: 344.1070; IR (neat, cm.sup.−1): ν 2924.64, 1738.29, 1517.78, 1252.31, 1222.75, 1115.15, 835.11, 719.94.

Example 29

(86) ##STR00037##

(87) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3b (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 6a was obtained by simple column chromatography with a yield of 76%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(88) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.39-7.32 (m, 2H), 7.01-6.94 (m, 2H), 4.36 (q, J=8.0 Hz, 2H), 3.85 (s, 3H), 3.19 (dt, J=13.9, 7.0 Hz, 1H), 1.40 (d, J=8.0 Hz, 6H), 1.32 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 169.13, 160.11, 157.52, 144.66, 130.93, 126.93, 113.85, 62.34, 55.44, 28.24, 21.45, 13.92. HRMS (ESI-TOF): Anal. Calcd. For C.sub.15H.sub.19N.sub.3O.sub.3+H.sup.+: 290.1499, Found: 290.1502; IR (neat, cm.sup.−1): ν 2975.31, 1729.47, 1520.10, 1487.75, 1256.44, 1288.07, 1121.29, 830.85.

Example 30

(89) ##STR00038##

(90) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3g (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 6f was obtained by simple column chromatography with a yield of 52%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(91) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.40-7.30 (m, 2H), 7.04-6.89 (m, 2H), 4.36 (q, J=8.0 Hz, 2H), 3.91-3.81 (m, 5H), 3.39 (s, 3H), 3.12 (t, J=7.0 Hz, 2H), 1.33 (t, J=8.0 Hz, 3H). 13C NMR (101 MHz, CDCl.sub.3) δ 161.68, 160.23, 157.35, 144.91, 130.77, 126.96, 113.89, 70.35, 62.48, 58.61, 55.51, 28.80, 13.98. HRMS (ESI-TOF): Anal. Calcd. For C.sub.15H.sub.19N.sub.3O.sub.4+H.sup.+: 306.1448, Found: 306.1459; IR (neat, cm.sup.−1): ν 2918.89, 1732.21, 1520.34, 1251.13, 1235.39, 1109.39, 1033.58, 832.50.

Example 31

(92) ##STR00039##

(93) Compound 1a (0.2 mmol, 45.8 mg), CuBr (0.04 mmol, 5.8 mg), Li.sub.2CO.sub.3 (14.8 mmol), compound 3h (0.5 ml) and compound 2a (0.6 mmol, 72.1 mg) were successively loaded into the reaction flask. Then the system was stirred at 40° C. in air for 1 hour, then quenched with ethyl acetate, the solvent was removed by rotary evaporator, and silica gel adsorption was carried out. The product 6g was obtained by simple column chromatography with a yield of 85%. The main test data of the product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.

(94) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.43-7.29 (m, 2H), 7.07-6.89 (m, 2H), 6.11 (m, 1H), 5.37-5.06 (m, 2H), 4.36 (q, J=8.0 Hz, 2H), 3.86 (s, 3H), 3.62 (dt, J=6.7, 1.3 Hz, 2H), 1.33 (t, J=8.0 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 162.56, 160.23, 157.32, 144.92, 133.27, 130.72, 126.94, 117.52, 113.89, 62.46, 55.48, 32.84, 13.96. HRMS (ESI-TOF): Anal. Calcd. For C.sub.15H.sub.17N.sub.3O.sub.3+H.sup.+: 288.1343, Found: 288.1337; IR (neat, cm.sup.−1): ν 2928.33, 1731.60, 1250.04, 1305.39, 1259.80, 1223.27, 1110.08, 853.01.