微波辅助无催化剂高效串联环化合成吡啶[2,3⁃d]嘧啶衍生物

doi:10.7503/cjcu20200563

摘要/Abstract

摘要：

建立了一种吡啶[2,3-d]嘧啶类化合物的高效合成方法. 以α,β?不饱和酮类化合物和1,3-二甲基-6-氨基脲嘧啶为原料, 在微波辅助无催化剂条件下, 于5~15 min内高效串联环化合成了28个具有分子多样性的吡啶[2,3-d]嘧啶类化合物, 其中21个化合物未见文献报道. 该方法具有原料简单易得、高效绿色、成键效率高及后处理简单等优点.

关键词: α,β-不饱和酮, 吡啶[2,3-d]嘧啶, 微波辅助, 无催化剂, 串联环化

Abstract:

This work presents a highly efficient and simple method for the synthesis of pyridine ［2，3-d］ pyrimidine derivatives. This method took the α，β-unsaturated ketones compounds and 1，3-dimethyl-6-aminouracil as raw material， 28 pyridine ［2，3-d］pyrimidine derivatives were synthesized by microwave irradiation high-efficiency tandem cyclization in 5―15 min without catalyst， including 21 compounds did not see the literature. This method has the characteristics of simple and easy raw materials， high green efficiency， high bonding efficiency and simple post-treatment.

Key words: α, β-Unsaturated ketone, Pyridine ［2, 3-d］pyrimidine, Microwave irradiation, Catalyst-free, Tandem cyclization

中图分类号:

O621.3

TrendMD:

林俊洁, 王爽, 李伟强, 崔鑫, 黄超. 微波辅助无催化剂高效串联环化合成吡啶[2,3⁃d]嘧啶衍生物. 高等学校化学学报, 2020, 41(12): 2749.

LIN Junjie, WANG Shuang, LI Weiqiang, CUI Xin, HUANG Chao. Efficient Synthesis of Pyridine ［2，3-d］pyrimidine Derivatives by Catalyst-free Tandem Cyclization Under Microwave Irradiation. Chem. J. Chinese Universities, 2020, 41(12): 2749.

图/表 7

Fig.1 Structures of bioactive pyridine [2,3?d]pyrimidines

Scheme 1 Synthesis of pyridine [2,3?d]pyrimidinone compounds by acid catalysis(A), carbonaceous material(B) and electrochemical catalysis(C)

Table 1 Appearance, yields, melting points, HRMS and IR data for compounds 3a—3x and 5a—5d

Compd.	Appearance	Yield^*(%)	m. p./℃(ref.)	HRMS, m/z[M+H]⁺	IR(KBr), $ν ?$ /cm^-1
3a	White solid	88	245—246(262—264)^[14]	344.1398	3067, 2906, 1705, 1663, 1555, 1420, 1363, 1004, 771, 701
3b	White solid	85	220—223	358.1557	3327, 2988, 1658, 1550, 1364, 1092, 821, 777, 698
3c	White solid	83	220—222	358.1555	3335, 2978, 1701, 1658, 1553, 1364, 1121, 747, 609
3d	Yellow solid	85	260—262	371.1711	3376, 2977, 1702, 1655, 1553, 1417, 1095, 747, 610
3e	White solid	79	231—233	358.1555	3284, 2980, 1704, 1657, 1364, 1095, 699, 608
3f	White solid	78	232—234	358.1557	3384, 2987, 1605, 1690, 1655, 1369, 1193, 812, 748
3g	White solid	81	214—216(217—219)^[14]	372.1713	3379, 2988, 1705, 1658, 1655, 1363, 1093, 802, 749
3h	White solid	78	253—254	374.1504	3356, 2976, 1655, 1551, 1416, 1367, 1243, 1178, 608, 569
3i	White solid	82	201—203	388.1661	3357, 2989, 1706, 1678, 1261, 1083, 800, 608
3j	White solid	81	228—231	404.1609	3354, 2968, 1704, 1654, 1600, 1089, 999, 787, 609
3k	White solid	80	241—243(259—260)^[14]	388.1661	3368, 2879, 1706, 1674, 1603, 1089, 998, 786, 605
3l	White solid	88	241—243	362.1306	3389, 2989, 1708, 1661, 1550, 1361, 1159, 1001, 608, 562
3m	White solid	85	251—253	378.1008	3354, 2968, 1655, 1567, 1365, 1094, 752, 609
3n	White solid	85	231—233	422.0505	3375, 2968, 1655, 1549, 1360, 1112, 1001, 751, 609
3o	White solid	84	235—237	376.1463	3389, 2988, 1666, 1567, 1546, 1153, 1096, 840, 799, 607
3p	White solid	84	232—233(238—239)^[14]	392.1167	3387, 2999, 1701, 1667, 1590, 1545, 1366, 1091, 799, 610
3q	White solid	82	230—232	436.0662	3375, 2976, 1705, 1592, 1543, 1361, 1086, 1003, 823, 750, 609
3r	Yellow solid	79	240—242	389.1252	3369, 2968, 1706, 1670, 1550, 1342, 1109, 521, 694, 609
3s	White solid	77	214—215	369.1351	3378, 2899, 2025, 1704, 1360, 1120, 608, 536
3t	White solid	78	215—217	360.1349	3397, 3066, 2948, 1710, 1670, 1551, 1367, 1224, 770, 746
3u	White solid	84	220—222	383.1509	3389, 2967, 1633, 1556, 1367, 1128, 999, 671
3v	Yellow solid	80	201—202	394.1555	3398, 2977, 1705, 1663, 1552, 1348, 1090, 767, 609
3w	Purple solid	81	238—240	350.0964	3386, 2988, 1709, 1656, 1415, 1097, 730, 607
3x	Yellow solid	81	217—218(213—215)^[33]	350.0965	3389, 2977, 2025, 1656, 1424, 1094, 800, 608
5a	White solid	70	165—166(171—178)^[12]	268.1083	3367, 2980, 1705, 1655, 1122, 608
5b	White solid	73	184—186	282.1235	3358, 2966, 1706, 1657, 1551, 1416, 1375, 754, 697, 550
5c	White solid	71	186—188	296.1941	3378, 2980, 2025, 1702, 1667, 2593, 1419, 753, 608
5d	White solid	78	185—186(180—182)^[12]	298.1193	3301, 3129, 2987, 1626, 1504, 1155, 1063, 754, 539

Table 1 Appearance, yields, melting points, HRMS and IR data for compounds 3a—3x and 5a—5d

Compd.	Appearance	Yield^*(%)	m. p./℃(ref.)	HRMS, m/z[M+H]⁺	IR(KBr), $ν ?$ /cm^-1
3a	White solid	88	245—246(262—264)^[14]	344.1398	3067, 2906, 1705, 1663, 1555, 1420, 1363, 1004, 771, 701
3b	White solid	85	220—223	358.1557	3327, 2988, 1658, 1550, 1364, 1092, 821, 777, 698
3c	White solid	83	220—222	358.1555	3335, 2978, 1701, 1658, 1553, 1364, 1121, 747, 609
3d	Yellow solid	85	260—262	371.1711	3376, 2977, 1702, 1655, 1553, 1417, 1095, 747, 610
3e	White solid	79	231—233	358.1555	3284, 2980, 1704, 1657, 1364, 1095, 699, 608
3f	White solid	78	232—234	358.1557	3384, 2987, 1605, 1690, 1655, 1369, 1193, 812, 748
3g	White solid	81	214—216(217—219)^[14]	372.1713	3379, 2988, 1705, 1658, 1655, 1363, 1093, 802, 749
3h	White solid	78	253—254	374.1504	3356, 2976, 1655, 1551, 1416, 1367, 1243, 1178, 608, 569
3i	White solid	82	201—203	388.1661	3357, 2989, 1706, 1678, 1261, 1083, 800, 608
3j	White solid	81	228—231	404.1609	3354, 2968, 1704, 1654, 1600, 1089, 999, 787, 609
3k	White solid	80	241—243(259—260)^[14]	388.1661	3368, 2879, 1706, 1674, 1603, 1089, 998, 786, 605
3l	White solid	88	241—243	362.1306	3389, 2989, 1708, 1661, 1550, 1361, 1159, 1001, 608, 562
3m	White solid	85	251—253	378.1008	3354, 2968, 1655, 1567, 1365, 1094, 752, 609
3n	White solid	85	231—233	422.0505	3375, 2968, 1655, 1549, 1360, 1112, 1001, 751, 609
3o	White solid	84	235—237	376.1463	3389, 2988, 1666, 1567, 1546, 1153, 1096, 840, 799, 607
3p	White solid	84	232—233(238—239)^[14]	392.1167	3387, 2999, 1701, 1667, 1590, 1545, 1366, 1091, 799, 610
3q	White solid	82	230—232	436.0662	3375, 2976, 1705, 1592, 1543, 1361, 1086, 1003, 823, 750, 609
3r	Yellow solid	79	240—242	389.1252	3369, 2968, 1706, 1670, 1550, 1342, 1109, 521, 694, 609
3s	White solid	77	214—215	369.1351	3378, 2899, 2025, 1704, 1360, 1120, 608, 536
3t	White solid	78	215—217	360.1349	3397, 3066, 2948, 1710, 1670, 1551, 1367, 1224, 770, 746
3u	White solid	84	220—222	383.1509	3389, 2967, 1633, 1556, 1367, 1128, 999, 671
3v	Yellow solid	80	201—202	394.1555	3398, 2977, 1705, 1663, 1552, 1348, 1090, 767, 609
3w	Purple solid	81	238—240	350.0964	3386, 2988, 1709, 1656, 1415, 1097, 730, 607
3x	Yellow solid	81	217—218(213—215)^[33]	350.0965	3389, 2977, 2025, 1656, 1424, 1094, 800, 608
5a	White solid	70	165—166(171—178)^[12]	268.1083	3367, 2980, 1705, 1655, 1122, 608
5b	White solid	73	184—186	282.1235	3358, 2966, 1706, 1657, 1551, 1416, 1375, 754, 697, 550
5c	White solid	71	186—188	296.1941	3378, 2980, 2025, 1702, 1667, 2593, 1419, 753, 608
5d	White solid	78	185—186(180—182)^[12]	298.1193	3301, 3129, 2987, 1626, 1504, 1155, 1063, 754, 539

Table 2 1H NMR and 13C NMR data for compounds 3a—3x and 5a—5d*

Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
3a	8.13—8.15(m, 2H), 7.52—7.50(m, 3H), 7.48—7.46(m, 4H), 7.37—7.33(m, 2H), 3.89(s, 3H), 3.39(s, 3H)	159.5, 158.2, 154.2, 150.8, 150.6, 138.6, 136.2, 129.7, 127.9, 127.2, 126.8, 126.5, 117.4, 105.5, 29.1, 27.4
3b	8.25—8.28(s, 1H), 7.57—7.50(m, 3H), 7.30—7.28(m, 2H), 7.24—7.22(m, 2H), 3.72(s, 3H), 3.19(s, 3H), 2.38(s, 3H)	159.8, 157.7, 154.4, 151.5, 151.0, 137.2, 136.8, 136.4, 130.7, 129.0, 128.3, 128.0, 127.5, 117.8, 106.4, 99.5, 29.8, 28.0, 20.9
3c	8.18—8.16(s, 1H), 7.57(s, 1H), 7.43—7.33(m, 7H), 3.72(s, 3H), 3.19(s, 3H), 2.38(s, 3H)	159.5, 158.2, 154.1, 150.8, 150.6, 140.2, 138.7, 133.5, 128.7, 127.1, 126.8, 126.5, 117.0, 105.6, 29.1, 27.4, 20.4
3d	7.90—7,87 (m, 2H), 7.48—7.44(m, 4H), 7.36—7.34(m, 2H), 7.27(s, 1H), 3.89(s, 3H), 3.39(s, 3H), 2.37—2.34(m, 6H)	159.6, 158.4, 154.0, 150.7, 150.6, 138.9, 138.7, 136.2, 133.9, 129.3, 127.6, 127.1, 126.8, 126.8, 124.1, 117.1, 105.2, 29.1, 27.4, 19.0, 18.8
3e	8.23—8.26(m, 3H), 7.58(d,J=8.0 Hz, 1H), 7.52—7.53(m, 3H), 7.29—7.27(m, 2H), 3.71(s, 3H), 3.19(s, 3H), 2.38(s, 3H)	159.5, 158.1, 154.4, 150.8, 150.6, 137.1, 136.3, 135.6, 129.7, 127.9, 127.6, 126.8, 126.5, 117.5, 105.6, 29.1, 27.4, 20.0
3f	8.15—8.13(m, 2H), 7.52—7.50(m, 3H), 7.47(s, 1H), 7.30—7.24(m, 3H), 7.24(s, 1H), 3.89(s, 3H), 3.40(s, 3H), 2.44(s, 3H)	159.5, 158.1, 154.4, 150.8, 150.6, 137.1, 136.3, 135.6, 129.7, 127.9, 127.6, 126.8, 126.5, 117.5, 105.6, 29.1, 27.4, 20.4
3g	8.02—8.04(m, 2H), 7.44(s, 1H), 7.32—7.27(m, 5H), 7.25(d, J=6.1 Hz, 1H), 3.88(s, 3H), 3.39(s, 3H), 2.44(d, J=3.8 Hz, 6H)	159.6, 158.1, 154.2, 150.8, 150.6, 140.1, 137.0, 135.7, 133.5, 128.7, 127.8, 126.8, 126.4, 117.1, 105.3, 29.1, 27.4, 20.4, 20.4
3h	8.26(d, J=9.0 Hz, 2H), 7.56(s, 1H), 7.43—7.41(m, 5H), 7.08(d, J=9.0 Hz, 2H), 3.84(s, 3H), 3.73(s, 3H), 3.19(s, 3H)	160.9, 159.5, 157.8, 154.0 150.8, 150.6, 138.7, 128.7, 128.1, 127.1, 126.8, 126.8, 116.5, 113.3, 104.8, 54.4, 29.1, 27.4
3i	8.04(d, J=8.2 Hz, 2H), 7.43(s, 1H), 7.31(d, J=8.7 Hz, 4H), 7.00(d, J=8.8 Hz, 2H), 3.88(d, J=0.5 Hz, 6H), 3.40(s, 3H), 2.43(s, 3H)	159.7, 158.7, 158.1, 153.9, 150.9, 150.6, 140.1, 133.6, 130.7, 128.8, 128.4, 126.4, 117.3, 112.3, 105.2, 54.3, 29.1, 27.4, 20.4
3j	8.10(d, J=8.9 Hz, 2H), 8.10(d, J=8.9 Hz, 2H), 7.38(s, 1H), 7.30(d, J=8.7 Hz, 2H), 7.00(m, 4H), 3.88—3.86(m, 8H), 3.39(s, 3H)	160.9, 159.6, 158.7, 157.6, 153.8, 150.9, 150.6, 130.8, 128.8, 128.4, 128.0, 116.8, 113.3, 112.3, 104.8, 54.4, 54.3, 29.1, 27.4
3k	8.10(d, J=8.9 Hz, 2H), 7.39(s, 1H), 7.28(d, J=8.1 Hz, 2H), 7.25(m, 2H), 7.01(d, J=8.9 Hz, 2H), 3.88(d, J=7.4 Hz, 6H), 3.39(s, 3H), 2.44(s, 3H)	160.9, 159.6, 157.7, 154.1, 150.8, 150.6, 137.0, 135.8, 128.8, 128.0, 127.6, 126.8, 116.6, 113.3, 104.9, 54.4, 29.1, 27.4, 20.4
3l	8.17—8.13(m, 2H), 7.49—7.48(m, 3H), 7.42(s, 1H), 7.34(m, 2H), 7.19(t, J=8.7 Hz, 2H), 3.88(s, 3H), 3.39(s, 3H)	164.8, 162.3, 159.4, 157.1, 154.4, 150.8, 150.5, 138.5, 132.4, 132.4, 128.6, 128.5, 127.2, 126.9, 126.7, 117.0, 115.1, 114.9, 105.5, 29.1, 27.4
3m	8.09—8.07(m, 2H), 7.48—7.47(m, 5H), 7.46—7.44(s, 1H), 7.35—7.33(m, 2H), 3.87(s, 3H), 3.39(s, 3H)	159.4 156.9, 154.5, 150.8, 150.5, 138.4, 136.0, 134.7, 128.2, 127.8, 127.3, 126.9, 126.7, 117.1, 105.7, 29.2, 27.5
3n	8.02—8.00(m, 2H), 7.65—7.63(m, 2H), 7.48—7.47(m, 3H), 7.44(s, 1H), 7.35—7.33(m, 2H), 3.87(s, 3H), 3.39(s, 3H)	159.4, 157.0, 154.5, 150.8, 150.5, 138.4, 135.1, 131.2, 128.0, 127.3, 126.7, 126.7, 124.5, 117.1, 105.8, 29.2, 27.5
3o	8.16—8.12(m, 2H), 7.41(s, 1H), 7.28(d, J=8.1 Hz, 2H), 7.23—7.17(m, 4H), 3.87(s, 3H), 3.39(s, 3H), 2.44(s, 3H)	164.7, 162.2, 159.5, 157.0, 154.6, 150.8, 150.5, 137.2, 135.5, 132.5, 132.5, 128.6, 128.5, 127.6, 126.8, 117.1, 115.1, 114.9, 105.5, 29.1, 27.4, 20.4
Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
3p	8.07(d, J=8.7 Hz, 2H), 7.47(d, J=8.7 Hz, 2H), 7.43(s, 1H), 7.28(d, J=8.0 Hz, 2H), 7.25—7.25(m, 2H), 3.87(s, 3H), 3.39(s, 3H), 2.44(s, 3H)	159.4, 156.8, 154.6, 150.9, 150.5, 137.2, 136.0, 135.4, 134.7, 128.2, 127.7, 127.6, 126.8, 117.2, 105.8, 29.2, 27.5, 20.4
3q	8.00(d, J=8.7 Hz, 2H), 7.63(d, J=8.7 Hz, 2H), 7.43(s, 1H), 7.28(d, J=8.0 Hz, 2H), 7.25—7.23(m, 2H), 3.87(s, 3H), 3.39(s, 3H), 2.44(s, 3H)	159.4, 156.9, 154.7, 150.9, 150.5, 137.2, 135.4, 135.2, 131.1, 128.0, 127.6, 126.8, 124.4, 117.2, 105.8, 29.2, 27.5, 20.4
3r	8.55(d, J=9.0 Hz, 2H), 8.34(d, J=9.0 Hz, 2H), 7.79(s, 1H), 7.45—7.41(m, 5H), 3.74(s, 3H), 3.20(s, 3H)	159.6, 155.3, 154.8, 151.6, 150.9, 148.5, 142.6, 139.1, 128.8, 128.3, 128.0, 127.5, 124.0, 119.0, 107.5, 29.9, 28.1
3s	8.26—8.24(m, 2H), 7.81—7.79(m, 2H), 7.50—7.46(m, 4H), 7.35—7.35(m, 2H), 3.88(s, 3H), 3.39(s, 3H)	159.2, 155.8, 154.9, 150.9, 150.3, 140.3, 138.1, 131.7, 127.5, 127.0, 127.0, 126.7, 117.8, 117.4, 113.0, 106.5, 29.2, 27.5
3t	13.20(s, 1H), 7.85—7.82(m, 1H), 7.57(s, 1H), 7.52—7.47(m, 1H), 7.44—7.38(m, 1H), 7.35(s, 1H), 7.07—7.05(m, 1H), 6.97—6.91(m, 1H), 3.82(s, 3H), 3.39(s, 3H)	159.2, 158.7, 154.8, 140.0, 139.4, 138.0, 132.6, 127.5, 127.0, 126.6, 118.6 117.8, 116.8, 116.4, 104.9, 29.5, 27.6
3u	8.25(d, J=8.4 Hz, 2H), 7.80(d, J=8.4 Hz, 2H), 7.50(s, 1H), 7.30—7.26(m, 2H), 7.24(s, 1H), 3.88(s, 3H), 3.40(s, 3H), 2.45(s, 3H)	159.2, 155.7, 155.1, 151.0, 150.4, 140.3, 137.5, 135.1, 131.7, 127.7, 127.0, 126.7, 118.0, 117.4, 113.0, 106.6, 29.2, 27.5, 20.4
3v	8.59(s, 1H), 8.27—8.25(m, 1H), 7.96—7.88(m, 3H), 7.62(s, 1H), 7.57—7.54(m, 2H), 7.51—7.49(m, 3H), 7.40—7.38(m, 2H), 3.93(s, 3H), 3.40(s, 3H)	159.5, 158.0, 154.2, 150.8, 150.5, 138.6, 133.5, 133.4, 132.2, 128.0, 127.7, 126.8, 126.7,126.7, 126.5, 125.6, 123.3, 117.5 105.5, 29.2, 27.4
3w	8.14—8.12(m, 2H), 7.60(s, 1H), 7.60—7.50(m, 4H), 7.26—7.24(m, 1H), 7.16—7.14(m, 1H), 3.87(s, 3H), 3.43(s, 3H)	159.3, 158.2, 151.0, 150.4, 146.71, 138.3, 136.0, 129.8, 127.9, 127.4, 126.5, 126.2, 125.9, 118.3, 105.7, 29.2, 27.5
3x	7.73—7.72(m, 1H), 7.56—7.54(m, 1H), 7.48—7.46(m, 3H), 7.35—7.33(m, 3H), 7.16—7.14(m, 1H), 3.83(s, 3H), 3.37(s, 3H)	159.3, 154.1, 153.3, 150.8, 150.5, 142.3, 138.4, 129.5, 127.5, 127.2, 126.8, 126.7, 126.4, 115.7, 105.1, 29.1, 27.4
5a	8.60(d, J=4.9 Hz, 1H), 7.46—7.44(m, 3H), 7.30—7.26(m, 2H), 7.01(d, J=4.9 Hz, 1H), 3.78(s, 3H), 3.37(s, 3H)	159.5, 153.5, 151.0, 150.3, 138.1, 127.2, 126.8, 121.0, 107.1, 29.2, 27.5
5b	7.44—7.42(m, 3H), 7.29—7.26(m, 2H), 6.87(s, 1H), 3.77(s, 3H), 3.36(s, 3H), 2.61(s, 3H)	161.6, 159.6, 153.4, 150.5, 138.4, 127.0, 126.7, 120.7, 104.5, 29.0, 27.3, 23.9
5c	7.25—7.23(m, 4H), 6.85(s, 1H), 3.76(s, 3H), 3.36(s, 3H), 2.60(s, 3H), 2.41(s, 3H)	161.5, 159.7, 153.6, 150.6, 150.6, 136.9, 135.4, 127.5, 126.7, 120.8, 104.6, 29.0, 27.4, 23.9, 20.3
5d	13.23(s, 1H), 7.52(s, 1H), 7.39—7.37(m, 1H), 7.04—7.02(m, 1H), 6.98—6.94(m, 1H), 3.74(s, 3H), 3.47(s, 3H), 2.91(s, 3H)	160.1, 159.1, 158.5, 153.7, 145.0, 149.3, 132.3, 126.3, 118.5, 117.7, 116.7, 116.2, 106.2, 29.4, 27.5, 22.1

Table 2 1H NMR and 13C NMR data for compounds 3a—3x and 5a—5d*

Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
3a	8.13—8.15(m, 2H), 7.52—7.50(m, 3H), 7.48—7.46(m, 4H), 7.37—7.33(m, 2H), 3.89(s, 3H), 3.39(s, 3H)	159.5, 158.2, 154.2, 150.8, 150.6, 138.6, 136.2, 129.7, 127.9, 127.2, 126.8, 126.5, 117.4, 105.5, 29.1, 27.4
3b	8.25—8.28(s, 1H), 7.57—7.50(m, 3H), 7.30—7.28(m, 2H), 7.24—7.22(m, 2H), 3.72(s, 3H), 3.19(s, 3H), 2.38(s, 3H)	159.8, 157.7, 154.4, 151.5, 151.0, 137.2, 136.8, 136.4, 130.7, 129.0, 128.3, 128.0, 127.5, 117.8, 106.4, 99.5, 29.8, 28.0, 20.9
3c	8.18—8.16(s, 1H), 7.57(s, 1H), 7.43—7.33(m, 7H), 3.72(s, 3H), 3.19(s, 3H), 2.38(s, 3H)	159.5, 158.2, 154.1, 150.8, 150.6, 140.2, 138.7, 133.5, 128.7, 127.1, 126.8, 126.5, 117.0, 105.6, 29.1, 27.4, 20.4
3d	7.90—7,87 (m, 2H), 7.48—7.44(m, 4H), 7.36—7.34(m, 2H), 7.27(s, 1H), 3.89(s, 3H), 3.39(s, 3H), 2.37—2.34(m, 6H)	159.6, 158.4, 154.0, 150.7, 150.6, 138.9, 138.7, 136.2, 133.9, 129.3, 127.6, 127.1, 126.8, 126.8, 124.1, 117.1, 105.2, 29.1, 27.4, 19.0, 18.8
3e	8.23—8.26(m, 3H), 7.58(d,J=8.0 Hz, 1H), 7.52—7.53(m, 3H), 7.29—7.27(m, 2H), 3.71(s, 3H), 3.19(s, 3H), 2.38(s, 3H)	159.5, 158.1, 154.4, 150.8, 150.6, 137.1, 136.3, 135.6, 129.7, 127.9, 127.6, 126.8, 126.5, 117.5, 105.6, 29.1, 27.4, 20.0
3f	8.15—8.13(m, 2H), 7.52—7.50(m, 3H), 7.47(s, 1H), 7.30—7.24(m, 3H), 7.24(s, 1H), 3.89(s, 3H), 3.40(s, 3H), 2.44(s, 3H)	159.5, 158.1, 154.4, 150.8, 150.6, 137.1, 136.3, 135.6, 129.7, 127.9, 127.6, 126.8, 126.5, 117.5, 105.6, 29.1, 27.4, 20.4
3g	8.02—8.04(m, 2H), 7.44(s, 1H), 7.32—7.27(m, 5H), 7.25(d, J=6.1 Hz, 1H), 3.88(s, 3H), 3.39(s, 3H), 2.44(d, J=3.8 Hz, 6H)	159.6, 158.1, 154.2, 150.8, 150.6, 140.1, 137.0, 135.7, 133.5, 128.7, 127.8, 126.8, 126.4, 117.1, 105.3, 29.1, 27.4, 20.4, 20.4
3h	8.26(d, J=9.0 Hz, 2H), 7.56(s, 1H), 7.43—7.41(m, 5H), 7.08(d, J=9.0 Hz, 2H), 3.84(s, 3H), 3.73(s, 3H), 3.19(s, 3H)	160.9, 159.5, 157.8, 154.0 150.8, 150.6, 138.7, 128.7, 128.1, 127.1, 126.8, 126.8, 116.5, 113.3, 104.8, 54.4, 29.1, 27.4
3i	8.04(d, J=8.2 Hz, 2H), 7.43(s, 1H), 7.31(d, J=8.7 Hz, 4H), 7.00(d, J=8.8 Hz, 2H), 3.88(d, J=0.5 Hz, 6H), 3.40(s, 3H), 2.43(s, 3H)	159.7, 158.7, 158.1, 153.9, 150.9, 150.6, 140.1, 133.6, 130.7, 128.8, 128.4, 126.4, 117.3, 112.3, 105.2, 54.3, 29.1, 27.4, 20.4
3j	8.10(d, J=8.9 Hz, 2H), 8.10(d, J=8.9 Hz, 2H), 7.38(s, 1H), 7.30(d, J=8.7 Hz, 2H), 7.00(m, 4H), 3.88—3.86(m, 8H), 3.39(s, 3H)	160.9, 159.6, 158.7, 157.6, 153.8, 150.9, 150.6, 130.8, 128.8, 128.4, 128.0, 116.8, 113.3, 112.3, 104.8, 54.4, 54.3, 29.1, 27.4
3k	8.10(d, J=8.9 Hz, 2H), 7.39(s, 1H), 7.28(d, J=8.1 Hz, 2H), 7.25(m, 2H), 7.01(d, J=8.9 Hz, 2H), 3.88(d, J=7.4 Hz, 6H), 3.39(s, 3H), 2.44(s, 3H)	160.9, 159.6, 157.7, 154.1, 150.8, 150.6, 137.0, 135.8, 128.8, 128.0, 127.6, 126.8, 116.6, 113.3, 104.9, 54.4, 29.1, 27.4, 20.4
3l	8.17—8.13(m, 2H), 7.49—7.48(m, 3H), 7.42(s, 1H), 7.34(m, 2H), 7.19(t, J=8.7 Hz, 2H), 3.88(s, 3H), 3.39(s, 3H)	164.8, 162.3, 159.4, 157.1, 154.4, 150.8, 150.5, 138.5, 132.4, 132.4, 128.6, 128.5, 127.2, 126.9, 126.7, 117.0, 115.1, 114.9, 105.5, 29.1, 27.4
3m	8.09—8.07(m, 2H), 7.48—7.47(m, 5H), 7.46—7.44(s, 1H), 7.35—7.33(m, 2H), 3.87(s, 3H), 3.39(s, 3H)	159.4 156.9, 154.5, 150.8, 150.5, 138.4, 136.0, 134.7, 128.2, 127.8, 127.3, 126.9, 126.7, 117.1, 105.7, 29.2, 27.5
3n	8.02—8.00(m, 2H), 7.65—7.63(m, 2H), 7.48—7.47(m, 3H), 7.44(s, 1H), 7.35—7.33(m, 2H), 3.87(s, 3H), 3.39(s, 3H)	159.4, 157.0, 154.5, 150.8, 150.5, 138.4, 135.1, 131.2, 128.0, 127.3, 126.7, 126.7, 124.5, 117.1, 105.8, 29.2, 27.5
3o	8.16—8.12(m, 2H), 7.41(s, 1H), 7.28(d, J=8.1 Hz, 2H), 7.23—7.17(m, 4H), 3.87(s, 3H), 3.39(s, 3H), 2.44(s, 3H)	164.7, 162.2, 159.5, 157.0, 154.6, 150.8, 150.5, 137.2, 135.5, 132.5, 132.5, 128.6, 128.5, 127.6, 126.8, 117.1, 115.1, 114.9, 105.5, 29.1, 27.4, 20.4
Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
3p	8.07(d, J=8.7 Hz, 2H), 7.47(d, J=8.7 Hz, 2H), 7.43(s, 1H), 7.28(d, J=8.0 Hz, 2H), 7.25—7.25(m, 2H), 3.87(s, 3H), 3.39(s, 3H), 2.44(s, 3H)	159.4, 156.8, 154.6, 150.9, 150.5, 137.2, 136.0, 135.4, 134.7, 128.2, 127.7, 127.6, 126.8, 117.2, 105.8, 29.2, 27.5, 20.4
3q	8.00(d, J=8.7 Hz, 2H), 7.63(d, J=8.7 Hz, 2H), 7.43(s, 1H), 7.28(d, J=8.0 Hz, 2H), 7.25—7.23(m, 2H), 3.87(s, 3H), 3.39(s, 3H), 2.44(s, 3H)	159.4, 156.9, 154.7, 150.9, 150.5, 137.2, 135.4, 135.2, 131.1, 128.0, 127.6, 126.8, 124.4, 117.2, 105.8, 29.2, 27.5, 20.4
3r	8.55(d, J=9.0 Hz, 2H), 8.34(d, J=9.0 Hz, 2H), 7.79(s, 1H), 7.45—7.41(m, 5H), 3.74(s, 3H), 3.20(s, 3H)	159.6, 155.3, 154.8, 151.6, 150.9, 148.5, 142.6, 139.1, 128.8, 128.3, 128.0, 127.5, 124.0, 119.0, 107.5, 29.9, 28.1
3s	8.26—8.24(m, 2H), 7.81—7.79(m, 2H), 7.50—7.46(m, 4H), 7.35—7.35(m, 2H), 3.88(s, 3H), 3.39(s, 3H)	159.2, 155.8, 154.9, 150.9, 150.3, 140.3, 138.1, 131.7, 127.5, 127.0, 127.0, 126.7, 117.8, 117.4, 113.0, 106.5, 29.2, 27.5
3t	13.20(s, 1H), 7.85—7.82(m, 1H), 7.57(s, 1H), 7.52—7.47(m, 1H), 7.44—7.38(m, 1H), 7.35(s, 1H), 7.07—7.05(m, 1H), 6.97—6.91(m, 1H), 3.82(s, 3H), 3.39(s, 3H)	159.2, 158.7, 154.8, 140.0, 139.4, 138.0, 132.6, 127.5, 127.0, 126.6, 118.6 117.8, 116.8, 116.4, 104.9, 29.5, 27.6
3u	8.25(d, J=8.4 Hz, 2H), 7.80(d, J=8.4 Hz, 2H), 7.50(s, 1H), 7.30—7.26(m, 2H), 7.24(s, 1H), 3.88(s, 3H), 3.40(s, 3H), 2.45(s, 3H)	159.2, 155.7, 155.1, 151.0, 150.4, 140.3, 137.5, 135.1, 131.7, 127.7, 127.0, 126.7, 118.0, 117.4, 113.0, 106.6, 29.2, 27.5, 20.4
3v	8.59(s, 1H), 8.27—8.25(m, 1H), 7.96—7.88(m, 3H), 7.62(s, 1H), 7.57—7.54(m, 2H), 7.51—7.49(m, 3H), 7.40—7.38(m, 2H), 3.93(s, 3H), 3.40(s, 3H)	159.5, 158.0, 154.2, 150.8, 150.5, 138.6, 133.5, 133.4, 132.2, 128.0, 127.7, 126.8, 126.7,126.7, 126.5, 125.6, 123.3, 117.5 105.5, 29.2, 27.4
3w	8.14—8.12(m, 2H), 7.60(s, 1H), 7.60—7.50(m, 4H), 7.26—7.24(m, 1H), 7.16—7.14(m, 1H), 3.87(s, 3H), 3.43(s, 3H)	159.3, 158.2, 151.0, 150.4, 146.71, 138.3, 136.0, 129.8, 127.9, 127.4, 126.5, 126.2, 125.9, 118.3, 105.7, 29.2, 27.5
3x	7.73—7.72(m, 1H), 7.56—7.54(m, 1H), 7.48—7.46(m, 3H), 7.35—7.33(m, 3H), 7.16—7.14(m, 1H), 3.83(s, 3H), 3.37(s, 3H)	159.3, 154.1, 153.3, 150.8, 150.5, 142.3, 138.4, 129.5, 127.5, 127.2, 126.8, 126.7, 126.4, 115.7, 105.1, 29.1, 27.4
5a	8.60(d, J=4.9 Hz, 1H), 7.46—7.44(m, 3H), 7.30—7.26(m, 2H), 7.01(d, J=4.9 Hz, 1H), 3.78(s, 3H), 3.37(s, 3H)	159.5, 153.5, 151.0, 150.3, 138.1, 127.2, 126.8, 121.0, 107.1, 29.2, 27.5
5b	7.44—7.42(m, 3H), 7.29—7.26(m, 2H), 6.87(s, 1H), 3.77(s, 3H), 3.36(s, 3H), 2.61(s, 3H)	161.6, 159.6, 153.4, 150.5, 138.4, 127.0, 126.7, 120.7, 104.5, 29.0, 27.3, 23.9
5c	7.25—7.23(m, 4H), 6.85(s, 1H), 3.76(s, 3H), 3.36(s, 3H), 2.60(s, 3H), 2.41(s, 3H)	161.5, 159.7, 153.6, 150.6, 150.6, 136.9, 135.4, 127.5, 126.7, 120.8, 104.6, 29.0, 27.4, 23.9, 20.3
5d	13.23(s, 1H), 7.52(s, 1H), 7.39—7.37(m, 1H), 7.04—7.02(m, 1H), 6.98—6.94(m, 1H), 3.74(s, 3H), 3.47(s, 3H), 2.91(s, 3H)	160.1, 159.1, 158.5, 153.7, 145.0, 149.3, 132.3, 126.3, 118.5, 117.7, 116.7, 116.2, 106.2, 29.4, 27.5, 22.1

Table 4 Synthesis of pyridine [2,3-d]pyrimidinone derivatives from chalconesa

Compd.	Product	Yield^b(%)	Time/min	Compd.	Product	Yield^b(%)	Time/min
3a		88	10	3h		78	13
3b		85	11	3i		82	15
3c		83	11	3j		81	15
3d		85	12	3k		80	13
3e		79	10	3l		88	10
3f		78	11	3m		85	10
3g		81	14	3n		85	11
Compd.	Product	Yield^b(%)	Time/min	Compd.	Product	Yield^b(%)	Time/min
3o		84	12	3t		78	15
3p		81	13	3u		84	13
3q		82	12	3v		80	13
3r		79	12	3w		81	11
3s		77	11	3x		83	10

Scheme 3 Possible mechanism of pyridine [2,3?d]pyrimidine synthesis

参考文献 34

1	Zhang H. J.， Wang S. B.， Wen X.， Li J. Z.， Quan Z. S.， Med. Chem. Res.， 2016， 25（7）， 1287—1298
2	Dongre R. S.， Meshram J. S.， Selokar R. S.， Almalki F. A.， Ben H. T.， New J. Chem.， 2018， 42（19）， 15610—15617
3	Gao X. G.， Cen L. Q.， Li F. Y.， Wen R.， Yan H. R.， Yao H.， Zhu S. L.， Biochem. Biophys. Res. Commun.， 2018， 505（3）， 761—767
4	Buron F.， Merour J. Y.， Akssira M.， Guillaumet G.， Routier S.， Eur. J. Med. Chem.， 2015， 95， 76—95
5	Shimizu M.， Takase Y.， Nakamura S.， Katae H.， Minami A.， Antimicrob.Agents Chemother.， 1975， 8（2）， 132—138
6	Acosta P.， Insuasty B.， Ortiz A.， Abonia R.， Sortino M.， Zacchino S. A.， Quiroga J.， Arabian J. Chem.， 2016， 9（3）， 481—492
7	Veeraswamy B.， Madhu D.， Dev G. J.， Poornachandra Y.， Kumar G. S.， Kumar C. G.， Narsaiah B.， Bioorg. Med. Chem. Lett.， 2018， 28（9）， 1670—1675
8	Fang F.， Xue L. M.， Cong J.， Tian C.， Wang X. W.， Liu J.， Zhang Z. L.， Chem. J. Chinese Universities， 2019， 40（10）， 2111—2120 （方芳，薛良敏，丛婧，田超，王孝伟，刘俊义，张志丽. 高等学校化学学报， 2019， 40（10）， 2111—2120）
9	Abbas S. E. S.， George R. F.， Samir E. M.， Aref M. M. A.， Abdel⁃Aziz H. A.， Future Med. Chem.， 2019， 11（18）， 2395—2414
10	Cheung A. W. H.， BanneB R.， Bose J.， Kim K.， Li S.， Marcopulos N.， Orzechowski L.， Sergi J. A.， Thakkar K. C.， Wang B. B.， Yun W.， Zwingelstein C.， Berthel S.， Olivier A. R.， Bioorg. Med. Chem. Lett.， 2012， 22（24）， 7518—7522
11	Lacbay C. M.， Mancuso J.， Lin Y. S.， Bennett N.， G€otte M.， Tsantrizos Y. S.， J. Med. Chem.， 2014， 57（17）， 7435—7449
12	Wawzonek S.， J. Org. Chem.， 1976， 41（19）， 3149—3151
13	Zhang F. R.， Li C. M.， Liang X. Z.， Green Chem.， 2018， 20（9）， 2057—2063
14	Shi D. Q.， Zhou Y.， Liu H.， J. Heterocycl. Chem.， 2010， 47， 131—135
15	Wang Z. S.， Wang M. Y.， Xu S. S.， Gu M. M.， Meng Z. Y.， Li C.， Cai P. J.， Rong L. C.， Synth. Commun.， 2016， 46（23）， 1887—1892
16	Farahmand T.， Hashemian S.， Sheibani A.， J. Mol. Struct.， 2020， 1206， 1—7
17	Upadhyay A.， Sharma L. K.， Singh V. K.， Singh R. K. P.， Tetrahedron Lett.， 2016， 57（50）， 5599—5604
18	Chate A. V.， Kulkarni A. S.， Jadhav C. K.， Nipte A. S.， Bondle G. M.， J. Heterocycl. Chem.， 2020， 57（5）， 2184—2193
19	Mamaghani M.， Sheykhan M.， Sadeghpour M.， Tavakoli F.， Monatsh Chem.， 2018， 149（8）， 1437—1446
20	Jiang L.， Ye W.， Su W.， Yu C.， Chem. Res. Chinese Universities， 2019， 35（1）， 21—25
21	Kappe C. O.， van der Eycken E.， Chem. Soc. Rev.， 2010， 39（4）， 1280—1290
22	Polshettiwar V.， Varma R. S.， Chem. Soc. Rev.， 2008， 37（8）， 1546—1557
23	Appukkuttan P.， Mehta V. P.， van der Eycken E.， Chem. Soc. Rev.， 2010， 39（5）， 1467—1477
24	Sharma A.， Appukkuttan P.， van der Eycken E.， Chem. Commun.， 2012， 48（11）， 1623—1637
25	Jiang Z.， Liu J.， Zhou F.， Zhang J.， Liu Z.， Zhang C.， Chen H.， Chem. Res. Chinese Universities， 2018， 34（6）， 918—922
26	Sun H. S.， Wang J. Q.， Guo C.， Shen L. J.， Chin. J. Org. Chem.， 2013， 33（10）， 2220—2225（孙宏顺，王建强，郭成，沈临江. 有机化学， 2013， 33（10）， 2220—2225）
27	Polshettiwar V.， Varma R. S.， Acc.Chem. Res.， 2008， 41（5）， 629—639
28	Kokel A.， Schafer C.， Torok B.， Green Chem.， 2017， 19（16）， 3729—3751
29	Bai H. R.， Sun R. R.， Chen X. B.， Yang L. J.， Huang C.， ChemistrySelect， 2018， 3（17）， 4635—4638
30	Bai H.， Sun R.， Liu S.， Yang L.， Chen X.， Huang C.， J. Org. Chem.， 2018， 83（20）， 12535—12548
31	Li J.， Duan W.， Pan X.， Ye Y.， Huang C.， ChemistrySelect， 2019， 4（12）， 3281—3285
32	Li J. S.， Li X. H.， Duan W. W.， Huang C.， Jouranl of Yunnan Minzu Universtiy（Natural Sciences Edition）， 2019， 117（05）， 444—451 （李济森，李新汉，段文文，黄超. 云南民族大学学报（自然科学版）， 2019， 117（05）， 444—451）
33	Majumdar K.， Ponra S.， Ghosh D.， Synthesis， 2011， 2011（7）， 1132—1136
34	Abdelrazek F. M.， Gomha S. M.， Abdel⁃aziz H. M.， Farghaly M. S.， Metz P.， Abdel⁃Shafy A.， J. Heterocycl. Chem.， 2020， 57（4）， 1759—1769

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