色烯并[4, 3-<i>d</i>]吡唑并[3, 4-<i>b</i>]吡啶衍生物的三组分合成及荧光性质研究

引用本文: 张梦烨, 王宁, 徐文韬, 黄志斌, 史达清. 色烯并[4, 3-d]吡唑并[3, 4-b]吡啶衍生物的三组分合成及荧光性质研究[J]. 有机化学, 2019, 39(4): 1085-1094. doi: 10.6023/cjoc201809042 shu

Citation: Zhang Mengye, Wang Ning, Xu Wentao, Huang Zhibin, Shi Daqing. Three-Component Synthesis of Chromeno[4, 3-d]pyrazolo[3, 4-b]-pyridine Derivatives and Their Fluorescence Properties[J]. Chinese Journal of Organic Chemistry, 2019, 39(4): 1085-1094. doi: 10.6023/cjoc201809042 shu

色烯并[4, 3-d]吡唑并[3, 4-b]吡啶衍生物的三组分合成及荧光性质研究

苏州大学材料与化学化工学部江苏省有机合成重点实验室苏州 215123

通讯作者: 黄志斌, zbhuang@suda.edu.cn; 史达清, dqshi@suda.edu.cn

基金项目:

江苏省高校自然科学重大研究（Nos.15KJA150006，17KJA150006）资助项目

摘要: 在三乙胺催化下，利用取代水杨醛、氰乙酸酯和5-氨基吡唑的三组分反应合成了一系列5-氨基色烯并[4，3-d]吡唑并[3，4-b]吡啶-6（3H）-酮衍生物4a~4v.荧光研究表明部分合成得到的化合物具有高的荧光量子产率.

关键词:

English

Three-Component Synthesis of Chromeno[4, 3-d]pyrazolo[3, 4-b]-pyridine Derivatives and Their Fluorescence Properties

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, Suzhou 215123

Corresponding author: Huang Zhibin, E-mail:zbhuang@suda.edu.cn; Shi Daqing, E-mail: dqshi@suda.edu.cn

Received Date: 29 September 2018
Revised Date: 10 December 2018
Available Online: 01 April 2019
Fund Project:

Project supported by the Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions (Nos. 15KJA150006, 17KJA150006)

Abstract: A series of 5-aminochromeno[4, 3-d]pyrazolo[3, 4-b]pyridin-6(3H)-one derivatives 4a~4w were synthesized by three-component reactions of salicylaldehydes, ethyl cyanoacetate and 5-aminopyrazoles catalyzed by triethylamine (TEA). The properties of the synthesized compounds were examined by fluorescence spectroscopy and the results indicated that some compounds were possessed high fluorescence quantum yields.

Key words:

chromeno[4, 3-d]pyrazolo[3, 4-b]pyridine
/ three-component synthesis
/ fluorescence property

香豆素又称2H-色烯-2-酮(2H-chromen-2-one)是一类重要的杂环化合物, 其骨架广泛存在于自然界, 其衍生物具有广泛的生物和药理活性, 如抗菌^[1]、抗炎^[2]、抗肿瘤^[3]、抗凝血^[4]和抗人类免疫缺陷病毒(HIV)^[5]等.另外, 由于色烯结构中存在大的共轭体系, 色烯衍生物具有很强是荧光性质, 同时还具有很高的光量子稳定性和光致发光量子产率^[6], 常被用作荧光团设计成荧光探针、激光染料、染料敏化剂、非线型光学材料和离子识别^[7]等.研究发现一些含有杂环稠合的色烯衍生物也具有很强的荧光性质, 例如色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮^[8].该类化合物一般采用含色烯骨架的酮与氨基吡唑的加成环化反应进行合成, 但收率较低(17%~23%)^[8], 后来通过改变反应的催化剂使反应的收率有了明显的提高^[9].鉴于色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮骨架具有很好的荧光性质, 合成新型官能团化的色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮引起了人们的广泛关注^[10].

多组分反应(MCRs)是指3个或3个以上组分进入反应, 用“一锅煮”的方法最终生成一个终产物, 在终产物结构中含有所有原料的片段的合成方法^[11].由于省去了中间产物的分离, 节省了大量的溶剂和时间, 同时, 它具有原子经济性, 使得多组分反应更加符合绿色化学的原则.多组分反应还可以通过底物的结构设计实现产物结构的多样性和复杂性, 多组分反应已经成为一些结构复杂的杂环化合物构建的有效方法^[12].近几年我们利用多组分反应构建了一些新型的杂环骨架^[13], 本文将报道5-氨基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物的三组分合成及其荧光性质研究.

1. 结果与讨论

1.1 5-氨基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物的合成

首先, 我们以水杨醛(1a)、氰乙酸乙酯(2)和3-甲基- 1-苯基-5-氨基吡唑(3a)的三组分反应(Eq. 1)为模板反应进行了反应条件的筛选, 结果见表 1.从表 1可以看出, 当反应在不加催化剂条件下在乙醇中回流反应24 h, 几乎得不到目标产物4a.在反应中加入10 mol%的对甲苯磺酸作为催化剂, 反应也不能进行(表 1, Entry 2).当用一价或二价铜盐作催化剂, 反应能发生, 但是产率较低(表 1, Entries 3, 4).当反应用无机碱(如碳酸钾)或有机碱(如哌啶、二乙胺、三乙胺)作催化剂时, 产率明显提高(表 1, Entries 5~8), 其中三乙胺的催化效果最好.我们还考察了有机小分子催化剂L-脯氨酸对该反应的催化活性(表 1, Entry 9), 结果表明催化活性不高.所以最终选择三乙胺为该反应的催化剂.考察溶剂对该反应的影响, 结果表明该反应在乙醇中明显比其它溶剂[如乙腈、N, N-二甲基甲酰胺(DMF)、甲苯、氯仿、四氢呋喃]中要好(表 1, Entries 8, 10~14), 所以选择乙醇作为该反应的溶剂.进一步考察了催化剂三乙胺用量对反应的影响(表 1, Entries 8, 15~17), 分别用5、10、15和20 mol%的三乙胺作催化剂, 产率分别为58%、63%、62%和60%, 说明催化剂的用量对反应的影响不大, 最后选择10 mol%的三乙胺作催化剂.考察了温度对该反应的影响(表 1, Entries 8, 18~20), 结果表明反应在回流下进行时产率最高.根据以上对反应条件的筛选, 得到的最佳反应条件是:以10 mol%的三乙胺作催化剂, 在乙醇中回流反应.

表 1

表 1 反应条件筛选^a

Table 1. Screening of reaction conditions

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Entry	Solvent	Catalyst (mol%)	T/℃	Time/h	Yield^b/%
1	EtOH	—	Reflux	24	Trace
2	EtOH	p-TSA (10)	Reflux	24	Trace
3	EtOH	CuSO₄ (10)	Reflux	14	16
4	EtOH	CuI (10)	Reflux	14	13
5	EtOH	K₂CO₃ (10)	Reflux	8	36
6	EtOH	Piperidine (10)	Reflux	8	52
7	EtOH	Et₂NH (10)	Reflux	8	58
8	EtOH	Et₃N (10)	Reflux	8	63
9	EtOH	L-Proline (10)	Reflux	10	35
10	CH₃CN	Et₃N (10)	Reflux	16	53
11	DMF	Et₃N (10)	120	4	46
12	Toluene	Et₃N (10)	110	24	40
13	CHCl₃	Et₃N (10)	Reflux	10	41
14	THF	Et₃N (10)	Reflux	15	36
15	EtOH	Et₃N (15)	Reflux	8	62
17	EtOH	Et₃N (20)	Reflux	8	60
18	EtOH	Et₃N (10)	20	20	36
19	EtOH	Et₃N (10)	40	18	52
20	EtOH	Et₃N (10)	60	11	55
^a Reaction conditions: 1a (1 mmol), 2 (1 mmol), 3a (1 mmol) in solvent (8 mL). ^b Yields were determined by HPLC-MS.

在最佳反应条件下, 研究了不同取代的水杨醛、氰乙酸乙酯及取代5-氨基吡唑的三组分反应(Eq. 2), 合成了一系列5-氨基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物4a~4v, 结果见表 2.从表 2可以看出, 水杨醛分子中的取代基对反应的影响不大, 无论是给电子取代基还是吸电子取代基, 都能得到中等左右的收率.当用乙酰乙酸乙酯(5)代替氰乙酸乙酯与水杨醛和5-氨基吡唑进行类似的三组分反应时, 也能得到预期的色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物(6) (Eq. 3), 但是产率较低, 其结果见表 3.

表 2

表 2 5-氨基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物4a~4w的合成

Table 2. Synthesis of 5-aminochromeno[4, 3-d]pyrazolo[3, 4-b]pyridin-6(3H)-one derivatives 4a~4w

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Entry	Product	R¹	R²	R³	R⁴	R⁵	Isolate yield/%
1	4a	H	H	H	Ph	CH₃	61
2	4b	H	H	Br	Ph	CH₃	58
3	4c	H	CH₃	H	Ph	CH₃	55
4	4d	CH₃O	H	H	Ph	CH₃	48
5	4e	H	CH₃O	H	Ph	CH₃	52
6	4f	H	H	CH₃O	Ph	CH₃	63
7	4g	H	H	H	CH₃	Ph	61
8	4h	H	CH₃O	H	CH₃	Ph	50
9	4i	H	H	H	CH₃	CH₃	66
10	4j	H	H	Cl	CH₃	CH₃	51
11	4k	H	H	Br	CH₃	CH₃	52
12	4l	H	CH₃	H	CH₃	CH₃	49
13	4m	CH₃O	H	H	CH₃	CH₃	61
14	4n	H	CH₃O	H	CH₃	CH₃	64
15	4o	H	H	CH₃O	CH₃	CH₃	66
16	4p	H	H	H	Ph	c-C₃H₅	62
17	4q	H	H	Cl	Ph	c-C₃H₅	52
18	4r	H	H	Br	Ph	c-C₃H₅	53
19	4s	H	CH₃	H	Ph	c-C₃H₅	63
20	4t	CH₃O	H	H	Ph	c-C₃H₅	60
21	4u	H	CH₃O	H	Ph	c-C₃H₅	54
22	4v	H	H	CH₃O	Ph	c-C₃H₅	67
23	4w	H	Et₂N	H	Ph	CH₃	65

表 3

表 3 色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物6a~6e的合成

Table 3. Synthesis of chromeno[4, 3-d]pyrazolo[3, 4-b]pyridin-6(3H)-one derivatives 6a~6e

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Entry	Product	R¹	R²	R³	R⁴	R⁵	Isolated yield/%
1	6a	H	H	H	Ph	CH₃	35
2	6b	H	CH₃O	H	Ph	CH₃	38
3	6c	H	CH₃	H	Ph	CH₃	40
4	6d	H	H	H	CH₃	CH₃	46
5	6e	H	H	CH₃O	CH₃	CH₃	49

产物的结构通过红外、核磁共振氢谱、核磁共振碳谱及高分辨质谱进行确定.化合物4a的结构还通过单晶X射线衍射进行了确定, 其晶体结构见图 1.

(1)

(2)

(3)

图 1

图 1. 化合物4a的单晶图

Figure 1. Crystal structure of compound 4a

下载: 全尺寸图片幻灯片

根据产物的结构及反应的规律, 推测该合成经历了如下过程(Scheme 1):首先取代水杨醛(1)在三乙胺催化下与氰乙酸乙酯(2)发生Knoevenagel缩合得中间体A, 中间体A通过分子内的环化得3-氰基香豆素(B), 5-氨基吡唑(3)与3-氰基香豆素发生Michael加成得中间体C, 中间体C通过分子内环化及互变异构化得中间体D, 中间体D通过氧化产物4.

图式1

图式1. 可能的反应机理

Scheme 1. Proposed reaction mechanism

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1.2 化合物3的荧光性质

研究了合成化合物的荧光性质, 化合物4a~4v在乙醇溶液中的荧光量子产率见表 3.从表 3可以看出:与香豆素151相比, 所合成化合物的λ_max(em)明显红移, 这说明这些化合物比香豆素151更容易激发.对比我们以前合成的色烯并[4, 3-d]吡唑并[3, 4-b]吡啶- 6(3H)-酮衍生物^{[9a, 10c]}, 该合成方法得到的5-氨基衍生物具有更大的激发态波长和更强的荧光强度, 同时荧光量子产率也有明显的提高(Scheme 2).另外, 化合物4b、4d、4e、4f、4u和4w在乙醇中具有高的量子产率, 有望通过结构修饰, 设计成新型的荧光材料或荧光探针.从表 4可以看出取代基的性质对荧光量子产率有明显的影响, 当产物的9位有共轭的给电子取代基(如二乙基氨基、甲氧基)时, 荧光量子产率较高, 而当产物10位有吸电子的取代基(如Cl、Br)时, 荧光量子产率较低.

图式2

图式2. 色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物荧光性质

Scheme 2. Fluorescence properties for chromeno[4, 3-d]pyrazolo[3, 4-b]pyridin-6(3H)-ones

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表 4

表 4 化合物4a~4w在乙醇溶液中的荧光量子产率^a

Table 4. Luminescence and fluorescence quantum yields of products 4a~4w in EtOH

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Compound	Purity^b/%	E_max(abs)/(L•mol^-1•cm^-1)	λ_max(ex)/nm	λ_max(em)/nm	RFI^c	Φ_F^d
Coumarin 151	98.50	0.8582	256.00	477.0	8870	0.749
4a	98.87	1.7258	264.00	491.0	4171	0.708
4b	98.76	0.3357	264.00	499.0	1941	0.064
4c	97.86	0.4754	266.00	488.0	4845	0.227
4d	98.43	2.0757	267.00	488.0	4308	0.880
4e	98.54	1.1118	268.00	472.0	6254	0.684
4f	98.42	1.6090	262.00	491.0	3981	0.630
4g	97.35	0.7068	271.00	494.0	4726	0.329
4h	98.95	0.7763	265.00	482.0	6494	0.496
4i	97.67	0.7493	268.00	489.0	4825	0.356
4j	98.01	0.8639	277.00	497.0	3522	0.299
4k	98.85	0.4512	278.00	494.0	3403	0.151
4l	98.28	0.9813	270.00	487.0	4553	0.440
4m	98.79	0.8093	269.00	485.0	4883	0.389
4n	97.38	0.8648	279.00	469.0	5705	0.485
4o	97.68	0.7654	272.00	489.0	4559	0.343
4p	98.57	1.8961	266.00	488.0	1811	0.338
4q	98.82	2.0655	265.00	508.0	1185	0.241
4r	98.61	2.3372	266.00	510.0	1083	0.249
4s	97.84	1.9172	267.00	500.0	2328	0.439
4t	98.47	2.0457	268.00	501.0	1961	0.395
4u	98.32	2.0555	270.00	493.0	3796	0.768
4v	98.02	2.0969	266.00	501.0	1772	0.366
4w	98.55	1.7235	267.00	474.0	6674	1.132
^a c＝5×10^-5 mol•L^-1. ^b The purity of resulting products gained by recrystallization was measured by HPLC. ^c Relative fluorescence intensity. ^d Relative fluorescence quantum yield.

2. 结论

以取代水杨醛、氰乙酸乙酯和5-氨基吡唑为原料, 利用三乙胺催化的多组分反应合成了一系列官能团化的5-氨基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物.并研究了这些化合物的荧光性质, 发现化合物4b、4d、4e、4f、4u和4w具有很强的荧光性和高的荧光量子产率, 为进一步的荧光性质研究奠定了基础.

3. 实验部分

3.1 试剂与仪器

熔点测定使用北京科仪电光仪器厂生厂的TX5显微熔点仪测定(温度未校正); 红外光谱采用Varian F-1000型红外光谱仪测定(KBr压片); 核磁共振氢谱和核磁共振碳谱在Agilent Inova-400MHz或Agilent Inova-300 MHz型核磁共振仪测定, DMSO-d₆或CF₃COOD为溶剂, TMS为内标; 高分辨质谱在Bruker MicrOTOF-QII质谱器测定, 采用电喷雾离子源(ESI)形式; 紫外-可见光谱在UV-2500PC型紫外可见分光光谱仪上测定; 荧光光谱在Hitachi F-4500荧光分光光度计上测定.

3.2 5-氨基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物(4a~4v)的合成通法

在25 mL干燥的园底烧瓶中加入水杨醛(1, 1 mmol)、氰乙酸乙酯(2, 1 mmol)、5-氨基吡唑(3, 1 mmol)、三乙胺(0.1 mmol)及8 mL乙醇.反应混合物在搅拌下加热回流反应6~20 h, 薄层色谱(TLC)检测反应进程.反应完成后, 冷却, 减压浓缩除去溶剂得粗产品, 粗产品用95%乙醇重结晶得纯产物4a~4w.

5-氨基-1-甲基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4a):黄色固体, m.p. 244~246 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.30 (s, 1H, NH₂-H), 8.10 (d, J＝7.2 Hz, 1H, ArH), 7.92 (d, J＝7.6 Hz, 2H, ArH), 7.87 (s, 1H, NH₂-H), 7.71 (t, J＝7.6 Hz, 1H, ArH), 7.49~7.40 (m, 4H, ArH), 7.31 (t, J＝7.6 Hz, 1H, ArH), 2.71 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.8, 159.4, 153.5, 152.2, 143.8, 139.1, 133.5, 129.8, 129.3, 126.1, 124.5, 121.4, 117.3, 116.6, 19.4; IR (KBr) ν: 3511, 3380, 3032, 1719, 1589, 1441, 1282, 1251, 1049, 826, 772, 685 cm^-1; HRMS (ESI) calcd for C₂₀H₁₅N₄O₂ [M+H]⁺ 343.1195, found 343.1194.

5-氨基-10-溴-1-甲基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4b):黄色固体, m.p.＞300 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.47 (s, 1H, ArH), 8.24 (s, 1H, NH₂-H), 8.17 (d, J＝7.6 Hz, 2H, ArH), 7.94 (s, 1H, NH₂-H), 7.88 (d, J＝8.0 Hz, 1H, ArH), 7.53~7.44 (m, 3H, ArH), 7.32 (t, J＝7.6 Hz, 1H, ArH), 2.72 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 162.0, 158.9, 152.4, 150.5, 142.7, 139.0, 136.1, 132.2, 129.5, 126.4, 123.0, 119.7, 117.1, 116.7, 19.5; IR (KBr) ν: 3440, 2935, 1722, 1616, 1511, 1440, 1251, 1021, 826, 753, 672 cm^-1; HRMS (ESI) calcd for C₂₀H₁₃BrN₄O₂ 420.0222, found 420.0219.

5-氨基-1, 9-二甲基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4c):黄色固体, m.p. 248~250 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.29 (s, 1H, NH₂-H), 8.21 (d, J＝7.9 Hz, 2H, ArH), 8.15 (s, 1H, ArH), 7.90 (s, 1H, NH₂-H), 7.56~7.51 (m, 3H, ArH), 7.39 (d, J＝8.4 Hz, 1H, ArH), 7.33 (t, J＝7.4 Hz, 1H, ArH), 2.76 (s, 3H, CH₃), 2.47 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.4, 159.1, 153.2, 149.9, 143.5, 143.5, 138.7, 133.9, 133.5, 129.0, 129.0, 125.8, 121.1, 116.7, 115.9, 104.0, 96.9, 30.7, 20.2, 19.0; IR (KBr) ν: 3423, 3310, 1688, 1588, 1554, 1479, 1276, 1232, 1069, 818, 753, 677 cm^-1; HRMS (ESI) calcd for C₂₁H₁₇N₄O₂ [M+H]⁺ 357.1352, found 357.1353.

5-氨基-8-甲氧基-1-甲基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4d):黄色固体, m.p. 262~263 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.26 (s, 1H, NH₂-H), 8.19 (d, J＝7.6 Hz, 2H, ArH), 7.91 (s, 1H, NH₂-H), 7.88~7.85 (m, 1H, ArH), 7.52 (t, J＝7.6 Hz, 2H, ArH), 7.42~7.41 (m, 2H, ArH), 7.31 (t, J＝7.6 Hz, 1H, ArH), 3.94 (s, 3H, CH₃O), 2.72 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.5, 159.5, 153.6, 147.5, 143.9, 141.9, 139.3, 129.4, 129.1, 126.2, 124.3, 121.5, 120.9, 115.6, 104.7, 56.7, 19.4; IR (KBr)ν: 3431, 3327, 3081, 1700, 1605, 1562, 1474, 1283, 1214, 1098, 789, 766, 742 cm^-1; HRMS (ESI) calcd for C₂₁H₁₆N₄O₃ 372.1222, found 372.1213.

5-氨基-9-甲氧基-1-甲基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4e):黄色固体, m.p. 247~248 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.33 (s, 1H, NH₂-H), 8.16~8.15 (m, 3H, ArH), 7.73 (s, 1H, NH₂-H), 7.48 (t, J＝7.2 Hz, 2H, ArH), 7.29 (t, J＝6.8 Hz, 1H, ArH), 7.00 (d, J＝8.0 Hz, 1H, ArH), 6.94 (s, 1H, ArH), 3.87 (s, 3H, CH₃O), 2.67 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.5, 160.2, 154.7, 151.3, 143.7, 141.9, 139.3, 130.4, 129.4, 126.1, 121.4, 116.3, 105.3, 105.1, 104.7, 101.2, 56.1, 19.5; IR (KBr) ν: 3421, 3320, 3070, 1697, 1610, 1508, 1477, 1259, 1170, 877, 759, 690 cm^-1; HRMS (ESI) calcd for C₂₁H₁₆N₄O₃ 372.1222, found 372.1206.

5-氨基-10-甲氧基-1-甲基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4f):黄色固体, m.p. 239~240 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.33 (s, 1H, NH₂-H), 8.19 (d, J＝6.4 Hz, 2H, ArH), 7.89 (s, 1H, NH₂- H), 7.78 (s, 1H, ArH), 7.53~7.32 (m, 5H, ArH), 3.92 (s, 3H, CH₃O), 2.80 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 159.6, 155.8, 149.9, 146.5, 143.7, 129.4, 126.2, 121.5, 121.0, 118.5, 117.2, 115.1, 112.5, 104.5, 100.1, 97.4, 56.5, 20.0; IR (KBr) ν: 3431, 3318, 3013, 1698, 1610, 1483, 1387, 1248, 1155, 811, 752, 693 cm^-1; HRMS (ESI) calcd for C₂₁H₁₆N₄O₃ 372.1222, found 372.1216.

5-氨基-3-甲基-1-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4g):黄色固体, m.p. 234~236 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.26 (s, 1H, NH₂-H), 7.84 (s, 1H, NH₂-H), 7.51~7.35 (m, 7H, ArH), 7.10 (d, J＝7.6 Hz, 1H, ArH), 6.62 (t, J＝7.6 Hz, 1H, ArH), 3.94 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.8, 159.4, 153.7, 152.3, 146.0, 143.4, 135.3, 133.1, 130.9, 129.5, 128.9, 128.8, 123.1, 116.8, 115.9, 101.1, 97.4, 33.9; IR (KBr) ν: 3451, 3335, 3046, 1696, 1603, 1454, 1364, 1268, 1052, 824, 764, 697 cm^-1; HRMS (ESI) calcd for C₂₀H₁₃N₄O₂ [M-H]^- 341.1039, found 341.1054.

5-氨基-9-甲氧基-3-甲基-1-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4h):黄色固体, m.p. 251~253 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.24 (s, 1H, NH₂-H), 7.78 (s, 1H, NH₂-H), 7.45~7.37 (m, 5H, ArH), 6.99 (d, J＝8.8 Hz, 1H, ArH), 6.95 (s, 1H, ArH), 6.17 (d, J＝8.4 Hz, 1H, ArH), 3.93 (s, 3H, CH₃), 3.80 (s, 3H, CH₃O); ¹³C NMR (100 MHz, DMSO-d₆) δ: 163.1, 162.0, 159.5, 154.6, 154.3, 153.7, 146.1, 143.6, 135.4, 132.0, 129.5, 128.9, 128.9, 111.1, 109.1, 100.8, 95.9, 56.4, 33.9; IR (KBr) ν: 3491, 3392, 3058, 1696, 1606, 1466, 1285, 1265, 1167, 877, 803, 778, 707 cm^-1; HRMS (ESI) calcd for C₂₁H₁₅N₄O₃[M-H]^- 371.1144, found 371.1127.

5-氨基-1, 3-二甲基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶- 6(3H)-酮(4i):黄色固体, m.p. 256~258 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.26 (d, J＝8.0 Hz, 1H, ArH), 8.14 (s, 1H, NH₂-H), 7.69 (t, J＝7.6 Hz, 1H, ArH), 7.62 (s, 1H, NH₂-H), 7.44 (t, J＝8.4 Hz, 2H, ArH), 3.75 (s, 3H, CH₃), 2.60 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.8, 159.1, 153.6, 152.2, 143.6, 141.4, 133.3, 129.5, 124.5, 117.3, 116.8, 102.8, 95.9, 33.4, 19.4; IR (KBr) ν: 3455, 3351, 2978, 1687, 1600, 1478, 1261, 1066, 821, 765, 687, 651 cm^-1; HRMS (ESI) calcd for C₁₅H₁₁N₄O₂ [M-H]^- 279.0882, found 279.0869.

5-氨基-10-氯-1, 3-二甲基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4j):黄色固体, m.p. 250~253 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.37 (s, 1H, ArH), 8.16 (s, 2H, NH₂-H), 7.77 (s, 1H, ArH), 7.54 (s, 1H, ArH), 3.81 (s, 3H, CH₃), 2.67 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.1, 158.7 153.3, 150.5, 142.0, 140.8, 132.5, 128.1, 128.0, 118.9, 117.9, 102.5, 96.3, 33.1, 19.0; IR (KBr) ν: 3376, 3175, 3024, 1701, 1629, 1512, 1439, 1259, 1056, 826, 720, 664 cm^-1; HRMS (ESI) calcd for C₁₅H₁₂ClN₄O₂ [M+H]⁺ 315.0649, found 315.0648.

5-氨基-10-溴-1, 3-二甲基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4k):黄色固体, m.p. 246~248 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.49 (s, 1H, ArH), 8.16 (s, 1H, NH₂-H), 7.89 (d, J＝8.6 Hz, 1H, ArH), 7.77 (s, 1H, NH₂-H), 7.46 (d, J＝8.6 Hz, 1H, ArH), 3.81 (s, 3H, CH₃), 2.66 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.0, 158.6, 153.3, 150.9, 141.9, 140.8, 135.2, 130.9, 119.2, 118.4, 115.6, 102.4, 96.3, 33.1, 19.0; IR (KBr) ν: 3380, 3181, 3022, 1703, 1631, 1512, 1443, 1261, 1254, 833, 705, 667 cm^-1; HRMS(ESI) calcd for C₁₅H₁₂BrN₄O₂ [M+H]⁺ 359.0144, found 359.0156.

5-氨基-1, 3, 9-三甲基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4l):黄色固体, m.p. 214~215 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.16 (s, 1H, NH₂-H), 8.03 (s, 1H, ArH), 7.64 (s, 1H, NH₂-H), 7.49 (d, J＝8.4 Hz, 1H, ArH), 7.30 (d, J＝8.4 Hz, 1H, ArH), 3.77 (s, 3H, CH₃), 2.61 (s, 3H, CH₃), 2.41 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO- d₆) δ: 161.5, 158.7, 153.1, 149.7, 143.2, 140.9, 133.6, 133.2, 128.6, 116.5, 116.0 102.3, 96.0, 33.0, 20.2, 19.0; IR (KBr) ν: 3371, 3174, 1688, 1612, 1513, 1442, 1266, 1227, 1064, 829, 763, 673 cm^-1; HRMS (ESI) calcd for C₁₆H₁₅N₄O₂ [M+H]⁺ 295.1195, found 295.1203.

5-氨基-8-甲氧基-1, 3-二甲基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4m):黄色固体, m.p. 282~284 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.19 (s, 1H, NH₂-H), 7.89 (t, J＝6.8 Hz, 1H, ArH), 7.72 (s, 1H, NH₂-H), 7.43~7.40 (m, 2H, ArH), 3.95 (s, 3H, CH₃), 3.81 (s, 3H, CH₃O), 2.66 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.7, 159.3, 152.1, 147.7, 143.7, 143.2, 141.4, 124.1, 123.5, 117.5, 114.2, 102.8, 95.8, 56.4, 33.4, 19.4; IR (KBr) ν: 3404, 3259, 2933, 1678, 1544, 1486, 1274, 1106, 822, 787, 731, 675 cm^-1; HRMS (ESI) calcd for C₁₆H₁₃N₄O₃[M-H]^- 309.0988, found 309.0979.

5-氨基-9-甲氧基-1, 3-二甲基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4n):黄色固体, m.p. 260~262 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.26 (d, J＝8.7 Hz, 1H, ArH), 8.17 (s, 1H, NH₂-H), 7.63 (s, 1H, NH₂-H), 7.05 (d, J＝8.7 Hz, 2H, ArH), 3.91 (s, 3H, OCH₃), 3.78 (s, 3H, CH₃), 2.64 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 163.0, 161.6, 158.9, 153.8, 153.3, 143.6, 141.1, 130.4, 111.9, 109.5, 102.1, 101.0, 94.7, 56.1, 33.0, 19.0; IR (KBr) ν: 3401, 3274, 3014, 1687, 1617, 1509, 1436, 1283, 1063, 838, 779, 687 cm^-1; HRMS (ESI) calcd for C₁₆H₁₅N₄O₃ [M+H]⁺ 311.1144, found 311.1138.

5-氨基-10-甲氧基-1, 3-二甲基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4o):黄色固体, m.p. 258~260 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.25 (s, 1H, NH₂-H), 7.76 (s, 1H, ArH), 7.67 (s, 1H, NH₂-H), 7.41 (d, J＝8.8 Hz, 1H, ArH), 7.31 (d, J＝8.8 Hz, 1H, ArH), 3.90 (s, 3H, CH₃O), 3.80 (s, 3H, CH₃N), 2.72 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 162.1, 159.4, 155.9, 153.8, 146.5, 143.7, 141.1, 120.8, 118.8, 112.2, 102.8, 100.0, 96.7, 56.3, 33.6, 20.0; IR (KBr) ν: 3385, 3267, 2975, 1690, 1627, 1481, 1278, 1198, 1072, 813, 765, 663 cm^-1; HRMS (ESI) calcd for C₁₆H₁₃N₄O₃ [M-H]^- 309.0988, found 309.0982.

5-氨基-1-环丙基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4p):黄色固体, m.p. 234~236 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.97 (d, J＝8.0 Hz, 1H, ArH), 8.29 (s, 1H, NH₂-H), 8.19 (d, J＝7.7 Hz, 2H, ArH), 7.91 (s, 1H, NH₂-H), 7.76~7.72 (m, 1H, ArH), 7.54~7.49 (m, 4H, ArH), 7.32 (t, J＝7.4 Hz, 1H, ArH), 2.29~2.19 (m, 1H, CH), 1.27~1.25 (m, 2H, CH₂), 1.21~1.17 (m, 2H, CH₂); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.2, 159.1, 153.2, 151.9, 147.7, 143.5, 138.8, 133.1, 129.7, 128.9, 125.8, 123.9, 121.1, 116.8, 116.3, 104.0, 96.8, 13.4, 9.3; IR (KBr) ν: 3497, 3366, 1707, 1582, 1503, 1445, 1305, 1246, 1052, 828, 751, 690 cm^-1; HRMS (ESI) calcd for C₂₂H₁₇N₄O₂ [M+H]⁺ 369.1352, found 369.1345.

5-氨基-10-氯-1-环丙基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4q):黄色固体, m.p. 220~221 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 9.05 (d, J＝2.4 Hz, 1H, ArH), 8.24 (s, 1H, NH₂-H), 8.17 (d, J＝7.7 Hz, 2H, ArH), 7.95 (s, 1H, NH₂-H), 7.76 (dd, J＝8.8, 2.4 Hz, 1H, ArH), 7.56~7.47 (m, 3H, ArH), 7.32 (t, J＝7.4 Hz, 1H, ArH), 2.26~2.15 (m, 1H, CH), 1.38~1.31 (m, 2H, CH₂), 1.24~1.19 (m, 2H, CH₂); ¹³C NMR (100 MHz, DMSO-d₆) δ: 160.9, 159.0, 153.2, 150.6, 147.2, 142.3, 138.6, 132.6, 128.9, 128.6, 128.0, 125.9, 121.1, 118.8, 117.8, 103.9, 96.9, 13.6, 9.4; IR (KBr) ν: 3476, 3344, 3124, 1714, 1608, 1509, 1433, 1247, 1026, 832, 752, 689 cm^-1; HRMS (ESI) calcd for C₂₂H₁₆ClN₄O₂ [M+H]⁺ 403.0962, found 403.0967.

5-氨基-10-溴-1-环丙基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4r):黄色固体, m.p. 219~221 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 9.17 (d, J＝1.9 Hz, 1H, ArH), 8.24 (s, 1H, NH₂-H), 8.17 (d, J＝8.0 Hz, 2H, ArH), 7.95 (s, 1H, NH₂-H), 7.87 (dd, J＝8.8, 2.0 Hz, 1H, ArH), 7.51 (t, J＝7.9 Hz, 2H, ArH), 7.45 (d, J＝8.8 Hz, 1H, ArH), 7.32 (t, J＝7.3 Hz, 1H, ArH), 2.18 (dd, J＝11.8, 6.6 Hz, 1H, CH), 1.34 (d, J＝3.0 Hz, 2H, CH₂), 1.26 (d, J＝7.7 Hz, 2H, CH₂); ¹³C NMR (100 MHz, DMSO-d₆) δ: 160.8, 159.0, 153.2, 151.0, 147.2, 142.2, 138.7, 135.4, 131.4, 129.0, 125.9, 121.1, 119.1, 118.3, 115.7, 103.9, 97.0, 13.6, 9.4; IR (KBr) ν: 3484, 3367, 3006, 1719, 1612, 1504, 1431, 1250, 1031, 814, 758, 689 cm^-1; HRMS (ESI) calcd for C₂₂H₁₆BrN₄O₂ [M+H]⁺ 447.0457, found 447.0460.

5-氨基-1-环丙基-9-甲基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4s):黄色固体, m.p. 199~200 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.73 (s, 1H, ArH), 8.29 (s, 1H, NH₂-H), 8.19 (d, J＝7.7 Hz, 2H, ArH), 7.88 (s, 1H, NH₂-H), 7.52 (t, J＝8.0 Hz, 3H, ArH), 7.41~7.28 (m, 2H, ArH), 2.44 (s, 3H, CH₃), 2.30~2.19 (m, 1H, CH), 1.35~1.28 (m, 2H, CH₂), 1.20~1.15 (m, 2H, CH₂); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.3, 159.1, 153.1, 149.9, 147.6, 143.5, 138.8, 133.9, 133.2, 129.2, 128.9, 125.8, 121.1, 116.5, 115.9, 103.9, 96.8, 30.7, 20.3, 13.5, 9.6; IR (KBr) ν: 3428, 3325, 2988, 1705, 1594, 1504, 1410, 1251, 1049, 840, 755, 673 cm^-1; HRMS (ESI) calcd for C₂₃H₁₉N₄O₂ [M+H]⁺ 383.1508, found 383.1508.

5-氨基-1-环丙基-8-甲氧基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4t):黄色固体, m.p. 263~264 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.45 (dd, J＝6.4, 2.8 Hz, 1H, ArH), 8.27 (s, 1H, NH₂-H), 8.17 (d, J＝7.9 Hz, 2H, ArH), 7.88 (s, 1H, NH₂-H), 7.51 (t, J＝7.9 Hz, 2H, ArH), 7.42~7.36 (m, 2H, ArH), 7.31 (t, J＝7.4 Hz, 1H, ArH), 3.93 (s, 3H, CH₃O), 2.26~2.15 (m, 1H, CH), 1.31~1.11 (m, 4H, 2×CH₂); ¹³C NMR (100 MHz, DMSO-d₆) δ: 162.5, 161.1, 159.2, 153.3, 147.9, 147.1, 144.0, 141.6, 138.8, 129.0, 125.9, 123.8, 121.3, 120.9 117.0, 115.2, 104.3, 97.0, 56.3, 30.9, 13.5, 9.5; IR (KBr) ν: 3485, 3358, 3010, 1687, 1581, 1503, 1436, 1271, 1086, 861, 756, 690 cm^-1; HRMS (ESI) calcd for C₂₃H₁₉N₄O₃ [M+H]⁺ 399.1457, found 399.1461.

5-氨基-1-环丙基-9-甲氧基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4u):黄色固体, m.p. 247~248 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.92 (d, J＝9.0 Hz, 1H, ArH), 8.26 (s, 1H, NH₂-H), 8.19 (d, J＝7.7 Hz, 2H, ArH), 7.84 (s, 1H, ArH), 7.52 (t, J＝7.9 Hz, 2H, ArH), 7.31 (t, J＝7.4 Hz, 1H, ArH), 7.18~7.03 (m, 2H, ArH), 3.92 (s, 3H, CH₃O), 2.23 (s, 1H, CH), 1.29~1.15 (m, 4H, 2×CH₂); ¹³C NMR (100 MHz, DMSO-d₆) δ: 163.2, 161.5, 159.2, 153.9, 153.3, 147.7, 143.8, 138.8, 131.0, 128.9, 125.8, 121.1, 111.7, 109.5, 103.6, 101.0, 95.4, 56.1, 13.5, 9.3; IR (KBr) ν: 3472, 3341, 3016, 1687, 1582, 1502, 1442, 1250, 1018, 840, 754, 690 cm^-1; HRMS (ESI) calcd for C₂₃H₁₉N₄O₃ [M+H]⁺ 399.1457, found 399.1466.

5-氨基-1-环丙基-10-甲氧基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4v):黄色固体, m.p. 222~223 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.37 (d, J＝2.8 Hz, 1H, ArH), 8.33 (s, 1H, NH₂-H), 8.18 (d, J＝7.7 Hz, 2H, ArH), 7.90 (s, 1H, NH₂-H), 7.52 (t, J＝7.9 Hz, 2H, ArH), 7.46 (d, J＝9.0 Hz, 1H, ArH), 7.40~7.29 (m, 2H, ArH), 3.87 (s, 3H, CH₃O), 2.36~2.25 (m, 1H, CH), 1.32~1.21 (m, 2H, CH₂), 1.20~1.11 (m, 2H, CH₂); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.3, 159.1, 155.3, 153.0, 147.7, 146.0, 143.3, 138.7, 128.9, 125.8, 121.1, 118.8, 117.7, 116.9, 114.3, 103.9, 96.9, 56.0, 30.7, 13.3, 9.8; IR (KBr) ν: 3420, 3320, 3005, 1702, 1589, 1507, 1438, 1246, 1059, 827, 752, 686 cm^-1; HRMS (ESI) calcd for C₂₃H₁₉- N₄O₃ [M+H]⁺ 399.1457, found 399.1468.

5-氨基-9-(二乙基氨基)-1-甲基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(4w):黄色固体, m.p. 190~192 ℃; ¹H NMR (400 MHz, CF₃COOD) δ: 8.86~8.80 (m, 1H, ArH), 7.97~7.93 (m, 2H, ArH), 7.77~7.69 (m, 3H, ArH), 7.62 (d, J＝7.2 Hz, 2H, ArH), 3.97 (q, J＝7.1 Hz, 4H, 2×CH₂N), 3.01 (s, 3H, CH₃), 1.40 (t, J＝7.2 Hz, 2×CH₃); ¹³C NMR (100 MHz, CF₃COOD) δ: 157.2, 156.7, 152.9, 150.2, 145.4, 144.4, 135.4, 135.1, 134.8, 133.2, 127.9, 121.7, 119.6, 118.7, 117.7, 115.9, 114.9, 107.4, 101.8, 57.9, 18.8, 11.6; IR (KBr) ν: 3373, 2976, 1682, 1581, 1518, 1349, 1262, 1092, 818, 795, 757 cm^-1; HRMS (ESI) calcd for C₂₄H₂₄N₅O₂ [M+H]⁺ 414.1930, found 414.1905.

3.3 色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物(6a~6e)的合成

在25 mL干燥的园底烧瓶中加入水杨醛(1, 1 mmol)、乙酰乙酸乙酯(5, 1 mmol)、5-氨基吡唑(3, 1 mmol)、三乙胺(0.1 mmol)及8 mL乙醇.反应混合物在搅拌下加热回流反应6~20 h, 薄层色谱(TLC)检测反应进程.反应完成后, 冷却, 减压浓缩除去溶剂得粗产品, 粗产品用95%乙醇重结晶得纯产物6a~6e.

1, 5-二甲基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶- 6(3H)-酮(6a):白色固体, m.p. 207~208 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.37 (d, J＝8.0 Hz, 1H, ArH), 8.21~8.19 (m, 2H, ArH), 7.78~7.74 (m, 1H, ArH), 7.62~7.58 (m, 2H, ArH), 7.55~7.50 (m, 2H, ArH), 7.41 (t, J＝8.0 Hz, 1H, ArH), 3.00 (s, 3H, CH₃), 2.86 (s, 3H, CH₃); ¹³C NMR (100 MHz, CF₃COOD) δ: 164.2, 157.3, 155.9, 151.6, 145.4, 142.2, 136.7, 136.2, 134.5, 134.4, 130.1, 129.7, 121.7, 119.9, 118.9, 117.7, 116.9, 116.1, 114.7, 25.7, 19.8; IR (KBr) ν: 3061, 1740, 1593, 1541, 1503, 1274, 1248, 1011, 811, 750, 659 cm^-1; HRMS (ESI) calcd for C₂₁H₁₅NaN₃O₂ [M+Na]⁺ 364.1062, found 364.1044.

9-甲氧基-1, 5-二甲基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(6b):白色固体, m.p. 227~229 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.31 (d, J＝9.7 Hz, 1H, ArH), 8.20 (d, J＝7.6 Hz, 2H, ArH), 7.60 (t, J＝8.0 Hz, 2H, ArH), 7.40 (t, J＝7.4 Hz, 1H, ArH), 7.11~7.09 (m, 2H, ArH), 3.93 (s, 3H, CH₃O), 2.98 (s, 3H, CH₃), 2.85 (s, 3H, CH₃); ¹³C NMR (100 MHz, CF₃COOD) δ: 172.9, 160.2, 155.3, 151.5, 145.2, 136.7, 136.2, 134.3, 130.0, 119.9, 118.9, 118.7, 117.1, 116.1, 115.7, 112.6, 111.2, 105.2, 59.4, 25.5, 19.8; IR (KBr) ν: 3068, 2940, 1733, 1616, 1540, 1504, 1469, 1278, 1024, 881, 753, 688 cm^-1; HRMS (ESI) calcd for C₂₂H₁₈N₃O₃ [M+H]⁺ 372.1348, found 372.1333.

1, 5, 10-三甲基-3-苯基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(6c):白色固体, m.p. 205~206 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.22~8.18 (m, 3H, ArH), 7.63~7.57 (m, 3H, ArH), 7.44~7.40 (m, 2H, ArH), 3.00 (s, 3H, CH₃), 2.88 (s, 3H, CH₃), 2.49 (s, 3H, CH₃); ¹³C NMR (100 MHz, CF₃COOD) δ: 166.4, 164.4, 155.9, 155.4, 151.6, 145.3, 143.4, 141.0, 136.7, 136.2, 134.2, 134.0, 130.0, 121.4, 117.4, 116.8, 114.6, 25.6, 22.5, 19.8; IR (KBr) ν: 3061, 2916, 1724, 1620, 1536, 1504, 1248, 1199, 1045, 804, 752, 669 cm^-1; HRMS (ESI) calcd for C₂₂H₁₈N₃O₂ [M+H]⁺ 356.1399, found 356.1374.

1, 3, 5-三甲基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶- 6(3H)-酮(6d):白色固体, m.p. 195~197 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.32 (d, J＝7.9 Hz, 1H, ArH), 7.72 (t, J＝7.7 Hz, 1H, ArH), 7.48 (t, J＝8.6 Hz, 2H, ArH), 4.02 (s, 3H, CH₃), 2.95 (s, 3H, CH₃), 2.75 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.4, 159.3, 151.9, 151.2, 141.8, 140.8, 133.1, 129.4, 124.1, 116.8, 116.2, 109.2, 106.5, 33.5, 30.7, 27.6, 18.6; IR (KBr) ν: 3000, 2934, 1721, 1610, 1516, 1372, 1247, 1189, 1044, 811, 753, 680 cm^-1; HRMS (ESI) calcd for C₁₆H₁₃NaN₃O₂ [M+ Na]⁺ 302.0905, found 302.0898.

10-甲氧基-1, 3, 5-三甲基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮(6e):白色固体, m.p. 204~205 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 7.81 (d, J＝2.9 Hz, 1H, ArH), 7.44 (d, J＝9.0 Hz, 1H, ArH), 7.33 (dd, J＝9.0, 2.9 Hz, 1H, ArH), 4.04 (s, 3H, CH₃O), 3.92 (s, 3H, CH₃O), 2.98 (s, 3H, CH₃), 2.85 (s, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 161.5, 159.5, 155.3, 151.2, 146.3, 141.8, 140.7, 120.5, 118.0, 116.7, 109.5, 106.6, 56.0, 33.6, 30.7, 27.7, 19.1; IR (KBr) ν: 3008, 2980, 1731, 1565, 1493, 1379, 1234, 1180, 1040, 812, 755, 649 cm^-1; HRMS (ESI) calcd for C₁₇H₁₅NaN₃O₃ [M+Na]⁺ 332.1011, found 332.0995.

辅助材料(Supporting Information) 化合物4a~4w和6a~6e的核磁共振氢谱和碳谱.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

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图 1 化合物4a的单晶图

Figure 1 Crystal structure of compound 4a

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图式1 可能的反应机理

Scheme 1 Proposed reaction mechanism

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图式2 色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物荧光性质

Scheme 2 Fluorescence properties for chromeno[4, 3-d]pyrazolo[3, 4-b]pyridin-6(3H)-ones

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表 1 反应条件筛选^a

Table 1. Screening of reaction conditions

Entry	Solvent	Catalyst (mol%)	T/℃	Time/h	Yield^b/%
1	EtOH	—	Reflux	24	Trace
2	EtOH	p-TSA (10)	Reflux	24	Trace
3	EtOH	CuSO₄ (10)	Reflux	14	16
4	EtOH	CuI (10)	Reflux	14	13
5	EtOH	K₂CO₃ (10)	Reflux	8	36
6	EtOH	Piperidine (10)	Reflux	8	52
7	EtOH	Et₂NH (10)	Reflux	8	58
8	EtOH	Et₃N (10)	Reflux	8	63
9	EtOH	L-Proline (10)	Reflux	10	35
10	CH₃CN	Et₃N (10)	Reflux	16	53
11	DMF	Et₃N (10)	120	4	46
12	Toluene	Et₃N (10)	110	24	40
13	CHCl₃	Et₃N (10)	Reflux	10	41
14	THF	Et₃N (10)	Reflux	15	36
15	EtOH	Et₃N (15)	Reflux	8	62
17	EtOH	Et₃N (20)	Reflux	8	60
18	EtOH	Et₃N (10)	20	20	36
19	EtOH	Et₃N (10)	40	18	52
20	EtOH	Et₃N (10)	60	11	55
^a Reaction conditions: 1a (1 mmol), 2 (1 mmol), 3a (1 mmol) in solvent (8 mL). ^b Yields were determined by HPLC-MS.

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表 2 5-氨基色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物4a~4w的合成

Table 2. Synthesis of 5-aminochromeno[4, 3-d]pyrazolo[3, 4-b]pyridin-6(3H)-one derivatives 4a~4w

Entry	Product	R¹	R²	R³	R⁴	R⁵	Isolate yield/%
1	4a	H	H	H	Ph	CH₃	61
2	4b	H	H	Br	Ph	CH₃	58
3	4c	H	CH₃	H	Ph	CH₃	55
4	4d	CH₃O	H	H	Ph	CH₃	48
5	4e	H	CH₃O	H	Ph	CH₃	52
6	4f	H	H	CH₃O	Ph	CH₃	63
7	4g	H	H	H	CH₃	Ph	61
8	4h	H	CH₃O	H	CH₃	Ph	50
9	4i	H	H	H	CH₃	CH₃	66
10	4j	H	H	Cl	CH₃	CH₃	51
11	4k	H	H	Br	CH₃	CH₃	52
12	4l	H	CH₃	H	CH₃	CH₃	49
13	4m	CH₃O	H	H	CH₃	CH₃	61
14	4n	H	CH₃O	H	CH₃	CH₃	64
15	4o	H	H	CH₃O	CH₃	CH₃	66
16	4p	H	H	H	Ph	c-C₃H₅	62
17	4q	H	H	Cl	Ph	c-C₃H₅	52
18	4r	H	H	Br	Ph	c-C₃H₅	53
19	4s	H	CH₃	H	Ph	c-C₃H₅	63
20	4t	CH₃O	H	H	Ph	c-C₃H₅	60
21	4u	H	CH₃O	H	Ph	c-C₃H₅	54
22	4v	H	H	CH₃O	Ph	c-C₃H₅	67
23	4w	H	Et₂N	H	Ph	CH₃	65

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表 3 色烯并[4, 3-d]吡唑并[3, 4-b]吡啶-6(3H)-酮衍生物6a~6e的合成

Table 3. Synthesis of chromeno[4, 3-d]pyrazolo[3, 4-b]pyridin-6(3H)-one derivatives 6a~6e

Entry	Product	R¹	R²	R³	R⁴	R⁵	Isolated yield/%
1	6a	H	H	H	Ph	CH₃	35
2	6b	H	CH₃O	H	Ph	CH₃	38
3	6c	H	CH₃	H	Ph	CH₃	40
4	6d	H	H	H	CH₃	CH₃	46
5	6e	H	H	CH₃O	CH₃	CH₃	49

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表 4 化合物4a~4w在乙醇溶液中的荧光量子产率^a

Table 4. Luminescence and fluorescence quantum yields of products 4a~4w in EtOH

Compound	Purity^b/%	E_max(abs)/(L•mol^-1•cm^-1)	λ_max(ex)/nm	λ_max(em)/nm	RFI^c	Φ_F^d
Coumarin 151	98.50	0.8582	256.00	477.0	8870	0.749
4a	98.87	1.7258	264.00	491.0	4171	0.708
4b	98.76	0.3357	264.00	499.0	1941	0.064
4c	97.86	0.4754	266.00	488.0	4845	0.227
4d	98.43	2.0757	267.00	488.0	4308	0.880
4e	98.54	1.1118	268.00	472.0	6254	0.684
4f	98.42	1.6090	262.00	491.0	3981	0.630
4g	97.35	0.7068	271.00	494.0	4726	0.329
4h	98.95	0.7763	265.00	482.0	6494	0.496
4i	97.67	0.7493	268.00	489.0	4825	0.356
4j	98.01	0.8639	277.00	497.0	3522	0.299
4k	98.85	0.4512	278.00	494.0	3403	0.151
4l	98.28	0.9813	270.00	487.0	4553	0.440
4m	98.79	0.8093	269.00	485.0	4883	0.389
4n	97.38	0.8648	279.00	469.0	5705	0.485
4o	97.68	0.7654	272.00	489.0	4559	0.343
4p	98.57	1.8961	266.00	488.0	1811	0.338
4q	98.82	2.0655	265.00	508.0	1185	0.241
4r	98.61	2.3372	266.00	510.0	1083	0.249
4s	97.84	1.9172	267.00	500.0	2328	0.439
4t	98.47	2.0457	268.00	501.0	1961	0.395
4u	98.32	2.0555	270.00	493.0	3796	0.768
4v	98.02	2.0969	266.00	501.0	1772	0.366
4w	98.55	1.7235	267.00	474.0	6674	1.132
^a c＝5×10^-5 mol•L^-1. ^b The purity of resulting products gained by recrystallization was measured by HPLC. ^c Relative fluorescence intensity. ^d Relative fluorescence quantum yield.

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