METHOD FOR PREPARING BETA-LACTAM DERIVATIVE

Abstract

The present invention relates to a method for preparing a β-lactam derivative, wherein a substituted N-quinoline-3-butenamide derivative is used as a substrate to react with a toluene derivative or a heterocyclic derivative at 90-150° C. in the presence of DTBP and a copper salt catalyst, to prepare a β-lactam derivative. According to the method of the present invention, a variety of β-lactam derivatives can be obtained with a high yield. The reaction of the present invention has mild reaction conditions, and simple reaction operation and post-treatment process, and is suitable for large-scale production.

Claims

1. A method for preparing a β-lactam derivative, comprising the steps of: reacting a substituted N-quinoline-3-butenamide derivative of Formula (1) and a toluene derivative of Formula (2) at 90-150° C. in the presence of di-tert-butyl peroxide and a copper salt catalyst, to give a β-lactam derivative of Formula (4), where the reaction route is as follows: ##STR00034## or reacting a substituted N-quinoline-3-butenamide derivative of Formula (1) and a heterocyclic derivative of Formula (3) at 90-150° C. in the presence of di-tert-butyl peroxide and a copper salt catalyst, to give a β-lactam derivative of Formula (5), where the reaction route is as follows: ##STR00035## wherein in Formulas (1)-(5), Y is an oxygen or sulfur atom; and R.sup.2 and R.sup.3 are hydrogen, and R.sup.1 is hydrogen, methyl, halo or trifluoromethyl; or R.sup.1 and R.sup.2 are hydrogen, and R.sup.3 is C1-C6 alkyl or benzyl; or R.sup.1 and R.sup.3 are hydrogen, and R.sup.2 is C1-C6 alkyl, allyl, benzyl, phenylethyl, cyclopropylmethyl, or cyclobutylmethyl.

2. The method according to claim 1, wherein the copper salt catalyst is selected from the group consisting of cuprous bromide, copper acetate, cuprous chloride, tetrakis(acetonitrile)copper hexafluorophosphate, copper trifluoromethanesulfonate, copper oxide, copper bromide and any combination thereof.

3. The method according to claim 1, wherein the molar ratio of the substituted N-quinoline-3-butenamide derivative: di-tert-butyl peroxide:copper salt catalyst=1:1-3:0.05-0.2.

4. The method according to claim 1, wherein the copper salt catalyst is tetrakis(acetonitrile)copper hexafluorophosphate.

5. The method according to claim 1, wherein the molar ratio of the substituted N-quinoline-3-butenamide derivative: di-tert-butyl peroxide:copper salt catalyst=1:3:0.05-0.2.

6. The method according to claim 1, wherein the reaction temperature is 130 to 150° C.

7. The method according to claim 1, wherein the reaction system also comprises, in addition to the toluene derivative of Formula (2) or the heterocyclic derivative of Formula (3), an additional organic solvent.

8. The method according to claim 7, wherein the organic solvent is selected from the group consisting of acetonitrile, tetrahydrofuran, N,N-dimethylformamide, isopropanol and any combination thereof.

Description

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0031] The specific embodiments of the present invention will be described in further detail with reference to examples. The following examples are intended to illustrate the present invention, instead of limiting the scope of the present invention.

Example 1: Synthesis of 4-phenethyl-1-(quinolin-8-yl)azetidin-2-one

[0032] ##STR00003##

[0033] (1) N-(8-quinolyl)-3-butenamidela (0.042 g, 0.2 mmol), and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2a. The yield after separation was 92%.

[0034] (2) N-(8-quinolyl)-3-butenamide 1a (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 110° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2a. The yield after separation was 80%.

[0035] (3) N-(8-quinolyl)-3-butenamide 1a (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 140° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2a. The yield after separation was 90%.

[0036] (4) N-(8-quinolyl)-3-butenamide 1a (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 90° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2a. The yield after separation was 22%.

[0037] (5) N-(8-quinolyl)-3-butenamide 1a (0.042 g, 0.2 mmol) and CuBr.sub.2 (0.005 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2a. The yield after separation was 56%.

[0038] (6) N-(8-quinolyl)-3-butenamide 1a (0.042 g, 0.2 mmol) and Cu(OAc).sub.2 (0.004 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2a. The yield after separation was 18%.

[0039] (7) N-(8-quinolyl)-3-butenamide 1a (0.042 g, 0.2 mmol) and CuBr (0.003 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2a. The yield after separation was 20%.

[0040] 2a: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.78 (dd, J=4.1, 1.8 Hz, 1H), 8.27 (dd, J=7.5, 1.4 Hz, 1H), 8.11 (dd, J=8.3, 1.7 Hz, 1H), 7.57 (dd, J=8.2, 1.4 Hz, 1H), 7.54-7.47 (m, 1H), 7.39 (dd, J=8.3, 4.1 Hz, 1H), 7.29-7.21 (m, 2H), 7.20-7.15 (m, 1H), 7.14-7.10 (m, 2H), 5.20 (ddd, J=11.8, 5.6, 2.9 Hz, 1H), 3.32 (dd, J=15.0, 5.3 Hz, 1H), 2.82 (dd, J=15.0, 2.6 Hz, 1H), 2.74-2.62 (m, 2H), 2.37 (tdd, J=9.1, 7.2, 3.3 Hz, 1H), 1.84 (dtd, J=13.3, 8.7, 6.4 Hz, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.46 (s), 148.92 (s), 141.10 (s), 140.65 (s), 136.03 (s), 133.61 (s), 128.99 (s), 128.38 (s), 128.29 (s), 126.70 (s), 126.02 (s), 124.01 (s), 121.63 (s), 121.32 (s), 56.11 (s), 43.12 (s), 35.24 (s), 31.63 (s). HRMS(ESI-TOF) Calcd for C.sub.20H.sub.19N.sub.2O [M+H].sup.+: 303.1497, found: 303.1512.

Example 2

Synthesis of 4-(3-methylphenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0041] ##STR00004##

[0042] N-(8-quinolyl)-3-butenamide 1b (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in m-xylene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2b. The yield after separation was 86%.

[0043] 2b: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.80 (dd, J=4.1, 1.8 Hz, 1H), 8.28 (dd, J=7.5, 1.4 Hz, 1H), 8.11 (dd, J=8.3, 1.8 Hz, 1H), 7.57 (dd, J=8.2, 1.4 Hz, 1H), 7.54-7.46 (m, 1H), 7.39 (dd, J=8.3, 4.1 Hz, 1H), 7.18-7.12 (m, 1H), 7.00 (d, J=7.6 Hz, 1H), 6.93 (d, J=6.5 Hz, 2H), 5.21 (ddd, J=11.7, 5.7, 3.0 Hz, 1H), 3.33 (dd, J=15.0, 5.3 Hz, 1H), 2.84 (dd, J=15.0, 2.6 Hz, 1H), 2.69-2.63 (m, 2H), 2.41-2.34 (m, 1H), 2.31 (s, 2H), 1.93-1.78 (m, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.05 (s), 148.48 (s), 140.59 (s), 140.22 (s), 137.45 (s), 135.56 (s), 133.18 (s), 128.62 (s), 128.53 (s), 127.83 (s), 126.28 (s), 126.23 (s), 124.83 (s), 123.58 (s), 121.19 (s), 120.86 (s), 55.70 (s), 42.65 (s), 34.78 (s), 31.05 (s), 20.92 (s); HRMS Calcd for C.sub.21H.sub.21N.sub.2O [M+H].sup.+: 317.1654, Found: 317.1669.

Example 3

Synthesis of 4-(4-methylphenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0044] ##STR00005##

[0045] N-(8-quinolyl)-3-butenamide 1c (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in p-xylene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2c. The yield after separation was 62%.

[0046] 2c: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.80 (dd, J=4.1, 1.8 Hz, 1H), 8.26 (dd, J=7.5, 1.4 Hz, 1H), 8.12 (dd, J=8.3, 1.7 Hz, 1H), 7.58 (dd, J=8.2, 1.4 Hz, 1H), 7.54-7.47 (m, 1H), 7.39 (dd, J=8.3, 4.1 Hz, 1H), 7.07 (d, J=7.9 Hz, 2H), 7.01 (d, J=8.1 Hz, 2H), 5.19 (ddd, J=11.8, 5.7, 3.0 Hz, 1H), 3.32 (dd, J=15.0, 5.3 Hz, 1H), 2.82 (dd, J=15.0, 2.6 Hz, 1H), 2.69-2.60 (m, 2H), 2.45-2.32 (m, 1H), 2.30 (s, 3H), 1.90-1.76 (m, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.55 (s), 148.95 (s), 140.68 (s), 138.00 (s), 136.04 (s), 135.47 (s), 133.64 (s), 129.06 (s), 129.00 (s), 128.15 (s), 126.70 (s), 124.04 (s), 121.67 (s), 121.33 (s), 56.18 (s), 43.09 (s), 35.30 (s), 31.15 (s), 21.00 (s); HRMS Calcd for C.sub.21H.sub.21N.sub.2O [M+H].sup.+: 317.1654, Found: 317.1668.

Example 4

Synthesis of 4-(2-methylphenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0047] ##STR00006##

[0048] N-(8-quinolyl)-3-butenamide 1d (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in o-xylene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2d. The yield after separation was 80%.

[0049] 2d: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.79 (dd, J=4.1, 1.8 Hz, 1H), 8.30 (dd, J=7.5, 1.5 Hz, 1H), 8.11 (dd, J=8.3, 1.8 Hz, 1H), 7.57 (dd, J=8.2, 1.4 Hz, 1H), 7.54-7.49 (m, 1H), 7.39 (dd, J=8.3, 4.1 Hz, 1H), 7.11-7.05 (m, 4H), 5.25 (ddd, J=11.6, 5.7, 3.0 Hz, 1H), 3.37 (dd, J=15.0, 5.3 Hz, 1H), 2.88 (dd, J=15.0, 2.6 Hz, 1H), 2.66 (t, J=8.0 Hz, 2H), 2.36-2.28 (m, 1H), 2.17 (s, 3H), 1.85-1.75 (m, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.02 (s), 148.43 (s), 140.12 (s), 138.84 (s), 135.59 (s), 135.24 (s), 133.21 (s), 129.75 (s), 128.53 (s), 128.17 (s), 126.26 (s), 125.70 (s), 125.54 (s), 123.54 (s), 121.08 (s), 120.86 (s), 55.80 (s), 42.66 (s), 33.70 (s), 28.45 (s), 18.60 (s). 43.09 (s), 35.30 (s), 31.15 (s), 21.00 (s); HRMS Calcd for C.sub.21H.sub.21N.sub.2O [M+H].sup.+: 317.1654, Found: 317.1693.

Example 5

Synthesis of 4-(2-chlorophenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0050] ##STR00007##

[0051] N-(8-quinolyl)-3-butenamide 1e (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in o-chlorotoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2e. The yield after separation was 83%.

[0052] 2e: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.77 (dd, J=4.1, 1.8 Hz, 1H), 8.28 (dd, J=7.5, 1.4 Hz, 1H), 8.11 (dd, J=8.3, 1.7 Hz, 1H), 7.57 (dd, J=8.1, 1.4 Hz, 1H), 7.52-7.47 (m, 1H), 7.39 (dd, J=8.3, 4.1 Hz, 1H), 7.31-7.28 (m, 1H), 7.15-7.08 (m, 3H), 5.23 (ddd, J=11.8, 5.6, 2.9 Hz, 1H), 3.36 (dd, J=15.0, 5.3 Hz, 1H), 2.88 (dd, J=15.0, 2.6 Hz, 1H), 2.79 (dd, J=8.7, 6.8 Hz, 2H), 2.36 (dtd, J=11.0, 8.0, 3.3 Hz, 1H), 1.90-1.78 (m, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 165.94 (s), 148.42 (s), 140.08 (s), 138.30 (s), 135.52 (s), 133.36 (s), 133.18 (s), 129.78 (s), 129.02 (s), 128.50 (s), 127.07 (s), 126.33 (s), 126.22 (s), 123.46 (s), 120.99 (s), 120.83 (s), 55.58 (s), 42.68 (s), 33.30 (s), 28.99 (s); HRMS Calcd for C.sub.20H.sub.18ClN.sub.2O [M+H].sup.+: 337.1108, Found: 317.1122.

Example 6

Synthesis of 4-(3-chlorophenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0053] ##STR00008##

[0054] N-(8-quinolyl)-3-butenamide 1f (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in m-chlorotoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2f. The yield after separation was 82%.

[0055] 2f: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.79 (dd, J=4.1, 1.8 Hz, 1H), 8.26 (dd, J=7.5, 1.4 Hz, 1H), 8.13 (dd, J=8.3, 1.8 Hz, 1H), 7.58 (dd, J=8.2, 1.4 Hz, 1H), 7.54-7.47 (m, 1H), 7.41 (dd, J=8.3, 4.1 Hz, 1H), 7.17 (dd, J=12.3, 5.0 Hz, 2H), 7.12 (s, 1H), 7.01-6.97 (m, 1H), 5.19 (ddd, J=11.8, 5.7, 3.0 Hz, 1H), 3.33 (dd, J=15.0, 5.3 Hz, 1H), 2.82 (dd, J=15.0, 2.6 Hz, 1H), 2.75-2.59 (m, 2H), 2.42-2.31 (m, 1H), 1.84 (dtd, J=13.4, 8.8, 6.0 Hz, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.24 (s), 149.00 (s), 143.08 (s), 140.56 (s), 136.07 (s), 134.15 (s), 133.53 (s), 129.61 (s), 129.00 (s), 128.35 (s), 126.72 (s), 126.58 (s), 126.23 (s), 124.05 (s), 121.57 (s), 121.38 (s), 55.81 (s), 43.09 (s), 34.84 (s), 31.28 (s); HRMS Calcd for C20H17ClN2ONa [M+Na].sup.+: 359.0927, Found: 359.0939.

Example 7

Synthesis of 4-(4-chlorophenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0056] ##STR00009##

[0057] N-(8-quinolyl)-3-butenamide 1 g (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in p-chlorotoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2g. The yield after separation was 83%.

[0058] 2 g: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.76 (dd, J=4.1, 1.8 Hz, 1H), 8.24 (dd, J=7.5, 1.4 Hz, 1H), 8.12 (dd, J=8.3, 1.7 Hz, 1H), 7.58 (dd, J=8.2, 1.3 Hz, 1H), 7.52-7.47 (m, 1H), 7.40 (dd, J=8.3, 4.1 Hz, 1H), 7.22-7.18 (m, 2H), 7.03 (d, J=8.4 Hz, 2H), 5.18 (ddd, J=11.7, 5.7, 3.0 Hz, 1H), 3.32 (dd, J=15.0, 5.3 Hz, 1H), 2.81 (dd, J=15.0, 2.6 Hz, 1H), 2.69-2.58 (m, 2H), 2.33 (tdd, J=9.2, 7.3, 3.3 Hz, 1H), 1.83 (dtd, J=13.4, 8.7, 6.3 Hz, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 165.82 (s), 148.44 (s), 140.12 (s), 139.04 (s), 135.60 (s), 133.05 (s), 131.25 (s), 129.14 (s), 128.52 (s), 127.97 (s), 126.24 (s), 123.59 (s), 121.14 (s), 120.88 (s), 55.42 (s), 42.57 (s), 34.58 (s), 30.46 (s); HRMS Calcd for C.sub.20H.sub.18ClN.sub.2O[M+H].sup.+: 337.1108, Found: 337.1118.

Example 8

Synthesis of 4-(2-(furan-2-yl)ethyl)-1-(quinolin-8-yl)azetidin-2-one

[0059] ##STR00010##

[0060] N-(8-quinolyl)-3-butenamide 1h (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in 2-methylfuran (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2h. The yield after separation was 80%.

[0061] 2h: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.82 (dd, J=4.1, 1.8 Hz, 1H), 8.25 (dd, J=7.5, 1.4 Hz, 1H), 8.13 (dd, J=8.3, 1.8 Hz, 1H), 7.58 (dd, J=8.2, 1.4 Hz, 1H), 7.54-7.48 (m, 1H), 7.40 (dd, J=8.3, 4.1 Hz, 1H), 7.27 (dd, J=1.8, 0.7 Hz, 1H), 6.26 (dd, J=3.1, 1.9 Hz, 1H), 5.98 (dd, J=3.1, 0.8 Hz, 1H), 5.23 (ddd, J=11.7, 5.7, 3.0 Hz, 1H), 3.31 (dd, J=15.1, 5.3 Hz, 1H), 2.76 (dd, J=15.1, 2.6 Hz, 1H), 2.70 (t, J=7.5 Hz, 2H), 2.41-2.33 (m, 1H), 1.93-1.83 (m, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 165.89 (s), 154.26 (s), 148.50 (s), 140.48 (s), 140.18 (s), 135.56 (s), 133.08 (s), 128.53 (s), 126.22 (s), 123.57 (s), 121.15 (s), 120.86 (s), 109.73 (s), 104.73 (s), 55.47 (s), 42.56 (s), 31.62 (s), 23.51 (s); HRMS Calcd for C.sub.18H.sub.17N.sub.2O.sub.2 [M+H.sup.+]: 293.1290, Found: 293.1300.

Example 9

Synthesis of 1-(quinolin-8-yl)-4-(2-(thiophen-2-yl)ethyl)azetidin-2-one

[0062] ##STR00011##

[0063] N-(8-quinolyl)-3-butenamide 1i (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in 2-methylthiophene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2i. The yield after separation was 65%.

[0064] 2i: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.81 (dd, J=4.1, 1.7 Hz, 1H), 8.26 (dd, J=7.5, 1.4 Hz, 1H), 8.13 (dd, J=8.3, 1.7 Hz, 1H), 7.58 (dd, J=8.2, 1.3 Hz, 1H), 7.54-7.48 (m, 1H), 7.40 (dd, J=8.3, 4.1 Hz, 1H), 7.10 (dd, J=5.1, 1.1 Hz, 1H), 6.89 (dd, J=5.1, 3.4 Hz, 1H), 6.76 (dd, J=2.3, 1.0 Hz, 1H), 5.25 (ddd, J=11.7, 5.7, 3.0 Hz, 1H), 3.33 (dd, J=15.0, 5.3 Hz, 1H), 2.91 (t, J=7.6 Hz, 2H), 2.83 (dd, J=15.0, 2.6 Hz, 1H), 2.43 (dtd, J=11.5, 8.0, 3.4 Hz, 1H), 1.92 (ddt, J=13.4, 9.1, 7.3 Hz, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 8.81 (dd, J=4.1, 1.7 Hz, 1H), 8.26 (dd, J=7.5, 1.4 Hz, 1H), 8.13 (dd, J=8.3, 1.7 Hz, 1H), 7.58 (dd, J=8.2, 1.3 Hz, 1H), 7.54-7.48 (m, 1H), 7.40 (dd, J=8.3, 4.1 Hz, 1H), 7.10 (dd, J=5.1, 1.1 Hz, 1H), 6.89 (dd, J=5.1, 3.4 Hz, 1H), 6.76 (dd, J=2.3, 1.0 Hz, 1H), 5.25 (ddd, J=11.7, 5.7, 3.0 Hz, 1H), 3.33 (dd, J=15.0, 5.3 Hz, 1H), 2.91 (t, J=7.6 Hz, 2H), 2.83 (dd, J=15.0, 2.6 Hz, 1H), 2.43 (dtd, J=11.5, 8.0, 3.4 Hz, 1H), 1.92 (ddt, J=13.4, 9.1, 7.3 Hz, 1H). 23.51; HRMS Calcd for C.sub.18H.sub.17N.sub.2OS [M+H].sup.+: 309.1062, Found: 309.1077.

Example 10

Synthesis of 4-(3-fluorophenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0065] ##STR00012##

[0066] N-(8-quinolyl)-3-butenamide 1j (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in m-fluorotoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2j. The yield after separation was 64%.

[0067] 2j: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.79 (dd, J=4.1, 1.8 Hz, 1H), 8.26 (dd, J=7.5, 1.4 Hz, 1H), 8.12 (dd, J=8.4, 1.7 Hz, 1H), 7.58 (dd, J=8.2, 1.3 Hz, 1H), 7.53-7.47 (m, 1H), 7.40 (dd, J=8.3, 4.1 Hz, 1H), 7.20 (td, J=7.8, 6.2 Hz, 1H), 6.91-6.82 (m, 3H), 5.19 (ddd, J=11.8, 5.6, 3.0 Hz, 1H), 3.32 (dd, J=15.0, 5.3 Hz, 1H), 2.81 (dd, J=15.0, 2.6 Hz, 1H), 2.75-2.62 (m, 2H), 2.45-2.31 (m, 1H), 1.90-1.77 (m, 1H). .sup.19F NMR (376 MHz, CDCl.sub.3) δ−113.64 (s). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 165.81 (s), 163.64 (s), 161.20 (s), 148.49 (s), 143.14 (d, J=7.2 Hz), 140.10 (s), 135.60 (s), 133.07 (s), 129.30 (d, J=8.4 Hz), 128.53 (s), 126.24 (s), 123.73-123.07 (m), 121.09 (s), 120.90 (s), 114.61 (d, J=21.0 Hz), 112.42 (d, J=20.9 Hz), 55.38 (s), 42.59 (s), 34.33 (s), 30.84 (s); HRMS Calcd for C.sub.20H.sub.18FN.sub.2O [M+H].sup.+: 321.1403, Found: 321.1400.

Example 11

Synthesis of 4-(2-fluorophenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0068] ##STR00013##

[0069] N-(8-quinolyl)-3-butenamide 1k (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in o-fluorotoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2k. The yield after separation was 82%.

[0070] 2k: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.73 (dd, J=4.1, 1.8 Hz, 1H), 8.27 (dd, J=7.5, 1.4 Hz, 1H), 8.10 (dd, J=8.3, 1.8 Hz, 1H), 7.55 (dd, J=8.2, 1.4 Hz, 1H), 7.52-7.45 (m, 1H), 7.37 (dd, J=8.3, 4.1 Hz, 1H), 7.19-7.08 (m, 2H), 7.04-6.92 (m, 2H), 5.19 (ddd, J=12.1, 5.5, 2.9 Hz, 1H), 3.33 (dd, J=15.0, 5.3 Hz, 1H), 2.83 (dd, J=15.1, 2.6 Hz, 1H), 2.71 (t, J=7.7 Hz, 2H), 2.37 (dtd, J=11.3, 8.0, 3.2 Hz, 1H), 1.89-1.73 (m, 2H). .sup.19F NMR (376 MHz, CDCl.sub.3) δ−118.68 (s). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 165.94 (s), 161.79 (s), 159.36 (s), 148.40 (s), 140.07 (s), 135.52 (s), 133.13 (s), 129.98 (d, J=4.9 Hz), 128.49 (s), 127.60 (s), 127.45 (s), 127.32 (d, J=8.1 Hz), 126.20 (s), 123.50 (d, J=4.0 Hz), 120.92 (d, J=16.5 Hz), 114.74 (d, J=22.1 Hz), 55.56 (s), 42.67 (s), 33.57 (s), 24.46 (d, J=2.6 Hz); HRMS Calcd for C.sub.20H.sub.18FN.sub.2O [M+H].sup.+: 321.1403, Found: 321.1398.

Example 12

Synthesis of 4-(2-bromophenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0071] ##STR00014##

[0072] N-(8-quinolyl)-3-butenamide 11 (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in o-bromotoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 21. The yield after separation was 82%.

[0073] 2l: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.77 (dd, J=4.1, 1.8 Hz, 1H), 8.28 (dd, J=7.5, 1.5 Hz, 1H), 8.10 (dd, J=8.3, 1.8 Hz, 1H), 7.56 (dd, J=8.2, 1.4 Hz, 1H), 7.52-7.45 (m, 2H), 7.38 (dd, J=8.3, 4.1 Hz, 1H), 7.15 (ddd, J=9.6, 7.4, 1.5 Hz, 2H), 7.05-6.99 (m, 1H), 5.24 (ddd, J=11.7, 5.6, 2.9 Hz, 1H), 3.36 (dd, J=15.0, 5.3 Hz, 1H), 2.90 (dd, J=15.0, 2.6 Hz, 1H), 2.78 (dd, J=9.1, 7.1 Hz, 2H), 2.34 (dtd, J=9.0, 7.9, 3.3 Hz, 1H), 1.87-1.80 (m, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 165.95 (s), 148.46 (s), 140.09 (s), 140.00 (s), 135.53 (s), 133.19 (s), 132.34 (s), 129.77 (s), 128.50 (s), 127.33 (s), 127.00 (s), 126.22 (s), 123.83 (s), 123.49 (s), 121.01 (s), 120.84 (s), 55.53 (s), 42.68 (s), 33.48 (s), 31.55 (s); HRMS Calcd for C.sub.20H.sub.18BrN.sub.2O [M+H].sup.+: 381.0603, Found: 381.0607.

Example 13

Synthesis of 4-(2-iodophenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0074] ##STR00015##

[0075] N-(8-quinolyl)-3-butenamide 1m (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in o-iodotoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2m. The yield after separation was 80%.

[0076] 2m: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.79 (dt, J=12.6, 6.3 Hz, 1H), 8.29 (dd, J=7.5, 1.4 Hz, 1H), 8.10 (dd, J=8.3, 1.7 Hz, 1H), 7.75 (dd, J=7.9, 1.1 Hz, 1H), 7.56 (dd, J=8.1, 1.4 Hz, 1H), 7.52-7.45 (m, 1H), 7.38 (dd, J=8.3, 4.1 Hz, 1H), 7.21 (td, J=7.5, 1.1 Hz, 1H), 7.12 (dd, J=7.6, 1.6 Hz, 1H), 6.84 (td, J=7.7, 1.7 Hz, 1H), 5.26 (ddd, J=11.6, 5.7, 3.0 Hz, 1H), 3.37 (dd, J=15.0, 5.3 Hz, 1H), 2.94 (dd, J=15.0, 2.6 Hz, 1H), 2.83-2.65 (m, 1H), 2.41-2.17 (m, 1H), 1.89-1.73 (m, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 165.93 (s), 148.53 (s), 143.25 (s), 140.13 (s), 139.03 (s), 135.54 (s), 133.21 (s), 128.82 (s), 128.53 (s), 127.92 (s), 127.46 (s), 126.24 (s), 123.50 (s), 121.05 (s), 120.85 (s), 99.84 (s), 55.46 (s), 42.71 (s), 36.20 (s), 33.83 (s); HRMS Calcd for C.sub.20H.sub.18BrN.sub.2O[M+H].sup.+: 429.0464, Found: 429.0474.

Example 14

Synthesis of 4-(3-iodophenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0077] ##STR00016##

[0078] N-(8-quinolyl)-3-butenamide in (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in m-iodotoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2n. The yield after separation was 62%.

[0079] 2n: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.79 (dd, J=4.1, 1.8 Hz, 1H), 8.24 (dd, J=7.5, 1.4 Hz, 1H), 8.13 (dd, J=8.4, 1.7 Hz, 1H), 7.58 (dd, J=8.2, 1.4 Hz, 1H), 7.54-7.46 (m, 3H), 7.41 (dd, J=8.3, 4.1 Hz, 1H), 7.07 (d, J=8.0 Hz, 1H), 6.98 (t, J=7.7 Hz, 1H), 5.18 (ddd, J=11.8, 5.7, 3.0 Hz, 1H), 3.32 (dd, J=15.0, 5.3 Hz, 1H), 2.81 (dd, J=15.0, 2.6 Hz, 1H), 2.70-2.52 (m, 2H), 2.34 (dddd, J=12.7, 9.2, 7.2, 3.3 Hz, 1H), 1.82 (dtd, J=13.4, 8.8, 5.9 Hz, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.26 (s), 149.06 (s), 143.53 (s), 140.57 (s), 137.23 (s), 136.08 (s), 135.13 (s), 133.50 (s), 130.11 (s), 129.00 (s), 127.68 (s), 126.71 (s), 124.09 (s), 121.59 (s), 121.40 (s), 94.51 (s), 55.82 (s), 43.09 (s), 34.91 (s), 31.17 (s); HRMS Calcd for C.sub.20H.sub.18BrN.sub.2O[M+H].sup.+: 429.0464, Found: 429.0472.

Example 15

Synthesis of 4-(4-iodophenethyl)-1-(quinolin-8-yl)azetidin-2-one

[0080] ##STR00017##

[0081] N-(8-quinolyl)-3-butenamide to (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in p-iodotoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2o. The yield after separation was 52%.

[0082] 2o: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.76 (dd, J=4.1, 1.8 Hz, 1H), 8.23 (dd, J=7.5, 1.3 Hz, 1H), 8.12 (dd, J=8.3, 1.7 Hz, 1H), 7.58 (dd, J=8.2, 1.3 Hz, 1H), 7.56-7.52 (m, 2H), 7.50 (t, J=7.8 Hz, 1H), 7.40 (dd, J=8.3, 4.1 Hz, 1H), 6.85 (d, J=8.3 Hz, 2H), 5.18 (ddd, J=11.6, 5.6, 3.0 Hz, 1H), 3.32 (dd, J=15.0, 5.3 Hz, 1H), 2.81 (dd, J=15.0, 2.6 Hz, 1H), 2.68-2.54 (m, 2H), 2.32 (tdd, J=9.1, 7.2, 3.3 Hz, 1H), 1.83 (dtd, J=13.5, 8.7, 6.3 Hz, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.29 (s), 148.92 (s), 140.72 (s), 140.58 (s), 137.37 (s), 136.09 (s), 133.51 (s), 130.38 (s), 128.99 (s), 126.73 (s), 124.08 (s), 121.62 (s), 121.37 (s), 91.01 (s), 55.89 (s), 43.04 (s), 34.93 (s), 31.09 (s); HRMS Calcd for C.sub.20H.sub.18BrN.sub.2O [M+H].sup.+: 429.0464, Found: 429.0472.

Example 16

Synthesis of 1-(quinolin-8-yl)-4-(2-(trifluoromethyl)phenethyl)azetidin-2-one

[0083] ##STR00018##

[0084] N-(8-quinolyl)-3-butenamide 1p (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in o-trifluoromethyltoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2p. The yield after separation was 76%.

[0085] 2p: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.81 (dd, J=4.1, 1.7 Hz, 1H), 8.28 (dd, J=7.5, 1.3 Hz, 1H), 8.11 (dd, J=8.3, 1.7 Hz, 1H), 7.60-7.54 (m, 2H), 7.50 (t, J=7.8 Hz, 1H), 7.40 (dd, J=8.3, 4.3 Hz, 2H), 7.23 (dd, J=13.9, 7.4 Hz, 2H), 5.26 (ddd, J=11.7, 5.6, 3.0 Hz, 1H), 3.38 (dd, J=15.0, 5.3 Hz, 1H), 2.88 (dd, J=15.0, 2.6 Hz, 1H), 2.86-2.75 (m, 2H), 2.44-2.30 (m, 1H), 1.92-1.76 (m, 1H). .sup.19F NMR (376 MHz, CDCl.sub.3) δ−59.65 (s). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.33 (s), 148.93 (s), 140.54 (s), 140.01 (s), 136.03 (s), 133.58 (s), 131.73 (s), 130.90 (s), 128.99 (s), 128.29 (dd, J=50.2, 20.6 Hz), 126.69 (s), 126.12 (s), 125.96 (q, J=272.0 Hz), 125.96 (d, J=5.7 Hz), 123.99 (s), 121.49 (s), 121.34 (s), 56.12 (s), 43.15 (s), 35.93 (s), 28.44 (s); HRMS Calcd for C.sub.21H.sub.17F.sub.3N.sub.2ONa [M+Na].sup.+: 393.1191, Found: 393.1196.

Example 17

Synthesis of 1-(quinolin-8-yl)-4-(3-(trifluoromethyl)phenethyl)azetidin-2-one

[0086] ##STR00019##

[0087] N-(8-quinolyl)-3-butenamide 1q (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in m-trifluoromethyltoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2q. The yield after separation was 64%.

[0088] 2q: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.75 (dd, J=4.1, 1.8 Hz, 1H), 8.25 (dd, J=7.5, 1.4 Hz, 1H), 8.12 (dd, J=8.4, 1.7 Hz, 1H), 7.58 (dd, J=8.2, 1.4 Hz, 1H), 7.54-7.47 (m, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.40 (dd, J=8.4, 4.2 Hz, 1H), 7.35 (d, J=7.2 Hz, 2H), 7.29 (d, J=7.4 Hz, 1H), 5.21 (ddd, J=11.7, 5.7, 3.1 Hz, 1H), 3.34 (dd, J=15.0, 5.3 Hz, 1H), 2.83 (dd, J=15.0, 2.6 Hz, 1H), 2.78-2.67 (m, 2H), 2.45-2.33 (m, 1H), 1.89 (dtd, J=13.4, 8.8, 6.2 Hz, 1H). .sup.19F NMR (376 MHz, CDCl.sub.3) δ−62.54 (s). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.22 (s), 148.95 (s), 141.98 (s), 140.57 (s), 136.10 (s), 133.47 (s), 131.74 (s), 130.70 (q, J=33.3 Hz), 129.01 (s), 128.80 (s), 126.71 (s), 125.35 (q, J=241.0 Hz), 124.92 (q, J=3.7 Hz), 124.13 (s), 122.94 (dd, J=7.5, 3.6 Hz), 121.64 (s), 121.39 (s), 55.81 (s), 43.07 (s), 34.98 (s), 31.44 (s); HRMS Calcd for C.sub.21H.sub.17F.sub.3N.sub.2ONa [M+Na.sup.+]: 393.1191, Found: 393.1198.

Example 18

Synthesis of 1-(quinolin-8-yl)-4-(4-(trifluoromethyl)phenethyl)azetidin-2-one

[0089] ##STR00020##

[0090] N-(8-quinolyl)-3-butenamide 1r (0.042 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in p-trifluoromethyltoluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 2r. The yield after separation was 48%.

[0091] 2r: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.75 (dd, J=4.1, 1.7 Hz, 1H), 8.24 (dd, J=7.5, 1.4 Hz, 1H), 8.12 (dd, J=8.3, 1.7 Hz, 1H), 7.58 (dd, J=8.1, 1.3 Hz, 1H), 7.50 (t, J=8.0 Hz, 3H), 7.40 (dd, J=8.3, 4.1 Hz, 1H), 7.21 (d, J=8.1 Hz, 2H), 5.21 (ddd, J=11.6, 5.6, 3.0 Hz, 1H), 3.34 (dd, J=15.0, 5.3 Hz, 1H), 2.84 (dd, J=15.0, 2.6 Hz, 1H), 2.74 (dt, J=14.0, 6.1 Hz, 2H), 2.43-2.32 (m, 1H), 1.90 (dtd, J=13.5, 8.8, 6.3 Hz, 1H). .sup.19F NMR (376 MHz, CDCl.sub.3) δ−62.36 (s). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.21 (s), 148.89 (s), 145.24 (s), 140.56 (s), 136.12 (s), 133.48 (s), 129.00 (s), 128.59 (s), 126.73 (s), 125.58 (q, J=268.7 Hz), 125.41 (d, J=4.0 Hz), 125.27 (dd, J=7.6, 3.8 Hz), 124.11 (s), 121.61 (s), 121.37 (s), 55.83 (s), 43.02 (s), 34.88 (s), 31.40 (s); HRMS Calcd for C.sub.21H.sub.18F.sub.3N.sub.2O [M+H.sup.+]: 371.1371, Found: 371.1382.

Example 19

Synthesis of 3-methyl-4-phenethyl-1-(quinolin-8-yl)azetidin-2-one

[0092] ##STR00021##

[0093] N-(8-quinolyl)-2-methyl-3-butenamide 3a (0.045 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4a. The yield after separation was 85%.

[0094] 4a: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.77 (dd, J=4.1, 1.7 Hz, 1H), 8.27 (dd, J=7.4, 1.4 Hz, 1H), 8.11 (dd, J=8.3, 1.7 Hz, 1H), 7.56 (dd, J=8.1, 1.3 Hz, 1H), 7.50 (t, J=7.8 Hz, 1H), 7.38 (dd, J=8.3, 4.1 Hz, 1H), 7.26 (dd, J=8.2, 6.6 Hz, 2H), 7.22-7.12 (m, 3H), 4.82 (dt, J=9.6, 2.7 Hz, 1H), 3.03 (qd, J=7.3, 2.2 Hz, 1H), 2.72 (t, J=7.7 Hz, 2H), 2.44-2.32 (m, 1H), 1.95-1.80 (m, 1H), 1.44 (d, J=7.4 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 169.54 (s), 148.37 (s), 140.71 (s), 140.15 (s), 135.50 (s), 133.09 (s), 128.53 (s), 127.90 (s), 127.85 (s), 126.23 (s), 125.55 (s), 123.33 (s), 121.20 (s), 120.78 (s), 63.98 (s), 50.68 (s), 34.45 (s), 31.33 (s), 13.26 (s); HRMS Calcd for C.sub.21H.sub.21N.sub.2O [M+H.sup.+]: 317.1654, Found: 317.1645.

Example 20

Synthesis of 3-ethyl-4-phenethyl-1-(quinolin-8-yl)azetidin-2-one

[0095] ##STR00022##

[0096] N-(8-quinolyl)-2-ethyl-3-butenamide 3b (0.048 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4b. The yield after separation was 82%.

[0097] 4b: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.79 (dd, J=4.1, 1.6 Hz, 1H), 8.30 (dd, J=7.4, 0.8 Hz, 1H), 8.11 (dd, J=8.3, 1.5 Hz, 1H), 7.56 (d, J=7.9 Hz, 1H), 7.50 (t, J=7.8 Hz, 1H), 7.39 (dd, J=8.3, 4.1 Hz, 1H), 7.25 (dd, J=9.0, 5.9 Hz, 2H), 7.20-7.11 (m, 3H), 4.93 (dt, J=9.3, 2.6 Hz, 1H), 3.01 (ddd, J=8.2, 6.2, 2.1 Hz, 1H), 2.71 (dd, J=8.6, 5.9 Hz, 2H), 2.46-2.28 (m, 1H), 2.06-1.93 (m, 1H), 1.91-1.80 (m, 2H), 1.15 (t, J=7.4 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 169.52 (s), 148.88 (s), 141.26 (s), 140.65 (s), 135.98 (s), 133.59 (s), 129.01 (s), 128.36 (s), 128.25 (s), 126.71 (s), 125.98 (s), 123.80 (s), 121.62 (s), 121.26 (s), 62.46 (s), 58.00 (s), 35.01 (s), 31.78 (s), 22.23 (s), 11.97 (s); HRMS Calcd for C.sub.22H.sub.22N.sub.2ONa[M+Na].sup.+:353.1630; Found: 353.1632.

Example 21

Synthesis of 4-phenethyl-3-propyl-1-(quinolin-8-yl)azetidin-2-one

[0098] ##STR00023##

[0099] N-(8-quinolyl)-2-propyl-3-butenamide 3c (0.051 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4c. The yield after separation was 75%.

[0100] 4c: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.79 (dd, J=4.1, 1.8 Hz, 1H), 8.30 (dd, J=7.4, 1.1 Hz, 1H), 8.11 (dd, J=8.4, 1.7 Hz, 1H), 7.56 (dd, J=8.2, 1.5 Hz, 1H), 7.53-7.46 (m, 1H), 7.39 (dd, J=8.3, 4.1 Hz, 1H), 7.26-7.23 (m, 2H), 7.17 (d, J=7.3 Hz, 1H), 7.12 (d, J=7.1 Hz, 2H), 4.92 (dt, J=9.3, 2.7 Hz, 1H), 3.06 (ddd, J=8.4, 6.2, 2.2 Hz, 1H), 2.70 (t, J=8.0 Hz, 2H), 2.44-2.29 (m, 1H), 2.02-1.87 (m, 2H), 1.85-1.75 (m, 1H), 1.66-1.49 (m, 2H), 1.01 (t, J=7.3 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 169.65 (s), 148.86 (s), 141.28 (s), 140.66 (s), 135.98 (s), 133.62 (s), 129.01 (s), 128.36 (s), 128.24 (s), 126.72 (s), 125.97 (s), 123.78 (s), 121.62 (s), 121.25 (s), 62.96 (s), 56.44 (s), 35.04 (s), 31.74 (s), 31.33 (s), 20.86 (s), 14.16 (s); HRMS Calcd for C.sub.23H.sub.25N.sub.2O [M+H].sup.+: 345.1967, Found: 345.1972.

Example 22

Synthesis of 3-isopropyl-4-phenethyl-1-(quinolin-8-yl)azetidin-2-one

[0101] ##STR00024##

[0102] N-(8-quinolyl)-2-isopropyl-3-butenamide 3d (0.051 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4d. The yield after separation was 73%.

[0103] 4d: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.82 (dd, J=4.1, 1.7 Hz, 1H), 8.32 (dd, J=7.4, 1.4 Hz, 1H), 8.11 (dd, J=8.3, 1.7 Hz, 1H), 7.56 (dd, J=8.1, 1.4 Hz, 1H), 7.50 (t, J=7.8 Hz, 1H), 7.39 (dd, J=8.3, 4.1 Hz, 1H), 7.24 (t, J=7.4 Hz, 2H), 7.18-7.10 (m, 3H), 5.05-5.00 (m, 1H), 2.91 (dd, J=7.8, 2.2 Hz, 1H), 2.70 (t, J=8.2 Hz, 2H), 2.38-2.28 (m, 1H), 2.22 (dq, J=13.7, 6.8 Hz, 1H), 1.95-1.83 (m, 1H), 1.22 (d, J=6.7 Hz, 3H), 1.15 (d, J=6.7 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 169.03 (s), 148.91 (s), 141.36 (s), 140.76 (s), 135.98 (s), 133.59 (s), 129.02 (s), 128.35 (s), 128.19 (s), 126.71 (s), 125.94 (s), 123.82 (s), 121.64 (s), 121.26 (s), 63.29 (s), 60.70 (s), 35.13 (s), 31.75 (s), 28.48 (s), 20.97 (s), 20.45 (s); HRMS Calcd for C.sub.23H.sub.25N.sub.2O [M+H].sup.+: 345.1967, Found: 345.1977.

Example 23

Synthesis of 3, 3-dimethyl-4-phenethyl-1-(quinolin-8-yl)azetidin-2-one

[0104] ##STR00025##

[0105] N-(8-quinolyl)-2,2′-dimethyl-3-butenamide 3e (0.048 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4e. The yield after separation was 52%.

[0106] 4e: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.75 (dd, J=4.1, 1.8 Hz, 1H), 8.17 (dd, J=7.5, 1.4 Hz, 1H), 8.09 (dd, J=8.3, 1.7 Hz, 1H), 7.56 (dd, J=8.2, 1.4 Hz, 1H), 7.54-7.44 (m, 1H), 7.37 (dd, J=8.3, 4.1 Hz, 1H), 7.25 (td, J=6.9, 1.8 Hz, 2H), 7.22-7.16 (m, 1H), 7.13-7.06 (m, 2H), 4.91 (dd, J=9.8, 3.7 Hz, 1H), 2.74-2.55 (m, 2H), 2.33-2.14 (m, 1H), 1.98-1.80 (m, 1H), 1.52 (s, 3H), 1.38 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 172.83 (s), 148.48 (s), 141.01 (s), 140.66 (s), 135.50 (s), 132.83 (s), 128.57 (s), 127.91 (s), 127.90 (s), 126.17 (s), 125.54 (s), 123.75 (s), 122.21 (s), 120.80 (s), 67.26 (s), 52.59 (s), 32.31 (s), 31.17 (s), 23.03 (s), 16.64 (s); HRMS Calcd for C.sub.22H.sub.22N.sub.2ONa [M+Na].sup.+: 353.1630, Found: 353.1643.

Example 24

Synthesis of 3-allyl-4-phenethyl-1-(quinolin-8-yl)azetidin-2-one

[0107] ##STR00026##

[0108] N-(8-quinolyl)-2-allyl-3-butenamide 3f (0.051 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4f. The yield after separation was 79%.

[0109] 4f: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.78 (dd, J=4.1, 1.7 Hz, 1H), 8.30 (dd, J=7.5, 1.4 Hz, 1H), 8.11 (dd, J=8.3, 1.7 Hz, 1H), 7.57 (dd, J=8.1, 1.4 Hz, 1H), 7.50 (t, J=7.8 Hz, 1H), 7.39 (dd, J=8.3, 4.1 Hz, 1H), 7.30-7.21 (m, 2H), 7.18 (d, J=7.3 Hz, 1H), 7.15-7.10 (m, 2H), 5.96 (ddt, J=17.1, 10.1, 7.0 Hz, 1H), 5.24 (dd, J=17.0, 1.5 Hz, 1H), 5.15 (d, J=10.1 Hz, 1H), 4.95 (dt, J=9.3, 2.8 Hz, 1H), 3.27-2.87 (m, 1H), 2.88-2.64 (m, 3H), 2.63-2.49 (m, 1H), 2.36 (tdd, J=9.3, 7.2, 3.2 Hz, 1H), 1.88 (dtd, J=13.4, 8.9, 6.7 Hz, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 168.75 (s), 148.93 (s), 141.26 (s), 140.63 (s), 135.98 (s), 134.99 (s), 133.52 (s), 129.01 (s), 128.36 (s), 128.29 (s), 126.69 (s), 125.99 (s), 123.92 (s), 121.65 (s), 121.29 (s), 117.38 (s), 62.41 (s), 56.00 (s), 34.91 (s), 33.31 (s), 31.78 (s); HRMS Calcd for C.sub.23H.sub.23N.sub.2O [M+H].sup.+: 343.1810, Found: 343.1810.

Example 25

Synthesis of 3-benzyl-4-phenethyl-1-(quinolin-8-yl)azetidin-2-one

[0110] ##STR00027##

[0111] N-(8-quinolyl)-2-benzyl-3-butenamide 3 g (0.061 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4g. The yield after separation was 84%.

[0112] 4 g: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.68 (dd, J=4.1, 1.8 Hz, 1H), 8.20 (dd, J=7.5, 1.5 Hz, 1H), 8.00 (dd, J=8.3, 1.7 Hz, 1H), 7.47 (dd, J=8.1, 1.3 Hz, 1H), 7.43-7.37 (m, 1H), 7.33-7.22 (m, 5H), 7.20-7.13 (m, 1H), 7.11-7.06 (m, 2H), 7.03 (dd, J=4.9, 3.5 Hz, 1H), 6.85-6.74 (m, 2H), 4.89 (dt, J=9.6, 2.4 Hz, 1H), 3.32-3.13 (m, 2H), 2.94 (dd, J=13.3, 9.4 Hz, 1H), 2.24-2.17 (m, 1H), 2.17-2.03 (m, 2H), 1.66 (ddt, J=10.5, 9.3, 8.0 Hz, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 168.74 (s), 148.98 (s), 141.29 (s), 140.68 (s), 139.20 (s), 136.00 (s), 133.47 (s), 129.02 (s), 128.71 (s), 128.26 (s), 128.15 (s), 126.70 (s), 126.65 (s), 125.85 (s), 124.05 (s), 121.79 (s), 121.32 (s), 62.93 (s), 58.37 (s), 35.35 (s), 34.79 (s), 31.20 (s); HRMS Calcd for C.sub.27H.sub.25N.sub.2O [M+H].sup.+: 393.1967, Found: 393.1967.

Example 26

Synthesis of 3, 4-diphenethyl-1-(quinolin-8-yl)azetidin-2-one

[0113] ##STR00028##

[0114] N-(8-quinolyl)-2-phenylethyl-3-butenamide 3h (0.063 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4h. The yield after separation was 80%.

[0115] 4h: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.76 (dd, J=4.1, 1.8 Hz, 1H), 8.24 (dd, J=7.5, 1.5 Hz, 1H), 8.07 (dd, J=8.3, 1.7 Hz, 1H), 7.53 (dd, J=8.2, 1.4 Hz, 1H), 7.50-7.42 (m, 1H), 7.35 (dd, J=8.3, 4.1 Hz, 1H), 7.26 (d, J=7.2 Hz, 2H), 7.23 (t, J=2.2 Hz, 2H), 7.21 (d, J=4.2 Hz, 2H), 7.18 (dd, J=4.5, 2.4 Hz, 1H), 7.13 (d, J=7.3 Hz, 1H), 7.08-7.04 (m, 2H), 4.99-4.89 (m, 1H), 3.03 (td, J=7.8, 2.2 Hz, 1H), 2.94-2.75 (m, 2H), 2.63 (t, J=7.9 Hz, 2H), 2.35-2.18 (m, 2H), 2.15-2.03 (m, 1H), 1.89-1.75 (m, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 169.27 (s), 148.92 (s), 141.44 (s), 141.15 (s), 140.71 (s), 136.00 (s), 133.52 (s), 129.02 (s), 128.59 (s), 128.49 (s), 128.46 (s), 128.38 (s), 128.26 (s), 126.72 (s), 126.02 (s), 123.92 (s), 121.72 (s), 121.29 (s), 62.90 (s), 55.84 (s), 34.83 (s), 33.58 (s), 31.70 (s), 30.92 (s); HRMS Calcd for C.sub.28H.sub.27N.sub.2O [M+H].sup.+: 407.2123, Found: 407.2134.

Example 27

Synthesis of 3-(cyclopropylmethyl)-4-phenethyl-1-(quinolin-8-yl)azetidin-2-one

[0116] ##STR00029##

[0117] N-(8-quinolyl)-2-methylcyclopropane-3-butenamide 3i (0.053 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4i. The yield after separation was 78%.

[0118] 4i: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.81 (dd, J=4.1, 1.8 Hz, 1H), 8.30 (dd, J=7.4, 1.4 Hz, 1H), 8.11 (dd, J=8.3, 1.8 Hz, 1H), 7.56 (dd, J=8.2, 1.5 Hz, 1H), 7.53-7.47 (m, 1H), 7.39 (dd, J=8.3, 4.1 Hz, 1H), 7.27-7.24 (m, 2H), 7.20-7.11 (m, 3H), 5.11-4.96 (m, 1H), 3.15 (ddd, J=8.4, 6.2, 2.2 Hz, 1H), 2.80-2.71 (m, 2H), 2.45-2.33 (m, 1H), 1.89 (ddd, J=13.1, 6.5, 3.3 Hz, 1H), 1.82-1.77 (m, 2H), 0.94 (tdd, J=7.6, 5.0, 2.6 Hz, 1H), 0.54 (dd, J=8.1, 1.4 Hz, 2H), 0.20 (ddd, J=16.1, 7.5, 3.1 Hz, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 169.47 (s), 148.89 (s), 141.34 (s), 140.68 (s), 135.99 (s), 133.62 (s), 129.03 (s), 128.37 (s), 128.23 (s), 126.72 (s), 125.98 (s), 123.82 (s), 121.65 (s), 121.27 (s), 62.77 (s), 56.96 (s), 35.10 (s), 34.00 (s), 31.79 (s), 9.25 (s), 5.11 (s), 4.55 (s); HRMS Calcd for C.sub.24H.sub.24N.sub.2ONa [M+H].sup.+:379.1786, Found: 379.1769.

Example 28

Synthesis of 3-(cyclobutylmethyl)-4-phenethyl-1-(quinolin-8-yl)azetidin-2-one

[0119] ##STR00030##

[0120] N-(8-quinolyl)-2-methylcyclobutane-3-butenamide 3j (0.055 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4j. The yield after separation was 75%.

[0121] 4j: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.80 (dd, J=4.1, 1.7 Hz, 1H), 8.28 (dd, J=7.4, 1.4 Hz, 1H), 8.11 (dd, J=8.3, 1.7 Hz, 1H), 7.56 (dd, J=8.1, 1.4 Hz, 1H), 7.53-7.47 (m, 1H), 7.39 (dd, J=8.3, 4.1 Hz, 1H), 7.25 (dd, J=9.0, 5.7 Hz, 2H), 7.19-7.11 (m, 3H), 4.97-4.88 (m, 1H), 2.97 (ddd, J=8.4, 6.0, 2.1 Hz, 1H), 2.68 (t, J=8.0 Hz, 2H), 2.57 (dt, J=15.4, 7.8 Hz, 1H), 2.33 (dtd, J=11.3, 8.2, 3.2 Hz, 1H), 2.15 (dtd, J=11.5, 7.6, 3.6 Hz, 2H), 2.05 (ddd, J=14.2, 8.4, 6.1 Hz, 1H), 1.96-1.90 (m, 2H), 1.89-1.83 (m, 2H), 1.76-1.68 (m, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 169.72 (s), 148.87 (s), 141.29 (s), 140.68 (s), 135.98 (s), 133.62 (s), 129.01 (s), 128.38 (s), 128.22 (s), 126.71 (s), 125.99 (s), 123.81 (s), 121.65 (s), 121.26 (s), 62.89 (s), 54.75 (s), 36.26 (s), 35.05 (s), 34.12 (s), 31.67 (s), 28.51 (s), 28.37 (s), 18.44 (s); HRMS Calcd for C.sub.25H.sub.27N.sub.2O [M+H].sup.+: 371.2123, Found: 371.2125.

Example 29

Synthesis of 4-(1-phenylpropan-2-yl)-1-(quinolin-8-yl)azetidin-2-one

[0122] ##STR00031##

[0123] N-(8-quinolyl)-3-pentenamide 3k (0.045 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4k. The yield after separation was 40%. 4k: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.86 (dd, J=4.1, 1.7 Hz, 1H), 8.14 (ddd, J=8.7, 7.9, 1.5 Hz, 2H), 7.64 (dd, J=8.2, 1.2 Hz, 1H), 7.53 (t, J=7.8 Hz, 1H), 7.42 (dd, J=8.3, 4.2 Hz, 1H), 7.08 (t, J=4.9 Hz, 3H), 6.81-6.75 (m, 2H), 5.24 (td, J=5.2, 2.7 Hz, 1H), 3.25 (dd, J=15.2, 5.6 Hz, 1H), 2.96 (dd, J=15.2, 2.7 Hz, 1H), 2.80 (dd, J=12.9, 3.4 Hz, 1H), 2.35-2.27 (m, 1H), 2.22 (dd, J=12.9, 10.3 Hz, 1H), 0.82 (d, J=6.6 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.69 (s), 149.18 (s), 141.52 (s), 140.25 (s), 136.09 (s), 133.92 (s), 129.03 (s), 128.83 (s), 128.13 (s), 126.71 (s), 125.81 (s), 124.68 (s), 122.84 (s), 121.40 (s), 60.38 (s), 39.40 (s), 37.52 (s), 36.87 (s), 15.66 (s); HRMS Calcd for C.sub.21H.sub.20N.sub.2ONa [M+Na].sup.+: 339.1473, Found: 339.1468.

Example 30

Synthesis of 4-(1-phenylbutan-2-yl)-1-(quinolin-8-yl)azetidin-2-one

[0124] ##STR00032##

[0125] N-(8-quinolyl)-3-hexenamide 31 (0.048 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 41. The yield after separation was 20%.

[0126] 4l: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.84 (dd, J=4.1, 1.8 Hz, 1H), 8.17-8.12 (m, 2H), 7.62 (dd, J=8.2, 1.3 Hz, 1H), 7.50 (dd, J=10.3, 5.4 Hz, 1H), 7.42 (dd, J=8.3, 4.1 Hz, 1H), 7.05-7.00 (m, 3H), 6.71-6.67 (m, 2H), 5.45 (td, J=5.7, 3.0 Hz, 1H), 3.21 (dd, J=15.2, 5.6 Hz, 1H), 3.00 (dd, J=15.2, 2.8 Hz, 1H), 2.76 (dd, J=13.4, 4.0 Hz, 1H), 2.35 (dd, J=13.4, 9.7 Hz, 1H), 2.22 (ddt, J=12.3, 8.4, 4.1 Hz, 1H), 1.42 (dtd, J=12.2, 7.5, 4.7 Hz, 1H), 1.24-1.18 (m, 1H), 0.93 (t, J=7.5 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.19 (s), 148.55 (s), 140.65 (s), 140.10 (s), 135.60 (s), 133.25 (s), 128.48 (s), 128.31 (s), 127.59 (s), 126.30 (s), 125.19 (s), 123.82 (s), 121.87 (s), 120.90 (s), 57.72 (s), 41.94 (s), 38.23 (s), 33.56 (s), 23.04 (s), 11.03 (s); HRMS Calcd for C.sub.22H.sub.23N.sub.2O [M+H.sup.+]:331.1810, Found: 331.1813.

Example 31

Synthesis of 4-(1,3-diphenylpropan-2-yl)-1-(quinolin-8-yl)azetidin-2-one

[0127] ##STR00033##

[0128] Compound 3m (0.060 g, 0.2 mmol) and Cu(CH.sub.3CN).sub.4PF.sub.6 (0.008 g, 0.02 mmol) were weighed and dissolved in toluene (1 mL), and DTBP (0.088 g, 0.6 mmol) was added. The mixture was heated to 130° C. and reacted until the reaction was completed as indicated by TLC. After the reaction, the crude product was separated and purified by column chromatography on silica gel (petroleum ether:ethyl acetate=10:1) to obtain the compound 4m. The yield after separation was 20%.

[0129] 4m: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.54 (dd, J=4.1, 1.8 Hz, 1H), 8.12 (ddd, J=5.1, 3.1, 1.6 Hz, 2H), 7.57 (dd, J=8.2, 1.3 Hz, 1H), 7.49-7.44 (m, 1H), 7.37 (dd, J=8.3, 4.1 Hz, 1H), 7.33-7.28 (m, 2H), 7.22 (dd, J=5.9, 3.5 Hz, 1H), 7.10 (d, J=6.9 Hz, 2H), 7.06-7.00 (m, 3H), 6.71 (dd, J=7.0, 2.4 Hz, 2H), 5.27 (dt, J=5.7, 3.0 Hz, 1H), 3.15 (dd, J=15.2, 5.6 Hz, 1H), 3.01 (dd, J=15.2, 2.9 Hz, 1H), 2.87-2.79 (m, 2H), 2.77 (d, J=4.1 Hz, 1H), 2.45-2.36 (m, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.30 (s), 148.74 (s), 140.65 (s), 140.13 (s), 139.82 (s), 135.96 (s), 133.72 (s), 129.01 (s), 128.83 (s), 128.74 (s), 128.29 (s), 128.20 (s), 126.79 (s), 126.15 (s), 125.84 (s), 123.95 (s), 121.67 (s), 121.27 (s), 57.88 (s), 42.61 (s), 38.28 (s), 37.34 (s), 34.08 (s); HRMS Calcd for C.sub.27H.sub.25N.sub.2O [M+H.sup.+]:393.1967, Found: 393.1972.

[0130] In summary, the present invention discloses a method for preparing a β-lactam derivative, in which a substituted N-quinoline-3-butenamide derivative is used as a substrate to react with toluene, a toluene derivative or a heterocyclic derivative at 90-150° C. in the presence of DTBP and a copper salt, to prepare a variety of β-lactam derivatives with a high yield.

[0131] While preferred embodiments of the present invention have been described above, the present invention is not limited thereto. It should be appreciated that some improvements and variations can be made by those skilled in the art without departing from the technical principles of the present invention, which are also contemplated to be within the scope of the present invention.