HETEROCYCLES

Paper | Regular issue | Vol. 83, No. 12, 2011, pp. 2811-2822
Received, 31st August, 2011, Accepted, 30th September, 2011, Published online, 7th October, 2011.
DOI: 10.3987/COM-11-12351

■ One-Step Synthesis of Tetrazolo[1,5-a]pyrimidines by Cyclization Reaction of Dihydropyrimidine-2-thiones with Sodium Azide

Xi-Cun Wang,* Ying Wei, Yu-Xia Da, Zhang Zhang, and Zheng-Jun Quan

Gansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070, China

Abstract

An novel, versatile and cost-effective approach for tetrazolo[1,5-a]pyrimidines and tetrazolo[1,5-a]quinazolines from cyclization reaction of dihydropyrimidinethiones with sodium azide in the presence of mercuric acetate is described. To compare this procedure with the conventional method, we carried out the cyclization reactions through direct functionalization of the pyrimidinethione core, which obtained from Biginelli 3,4-dihydropyrimidine-2-thiones or 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8- octahydroquinazoline-2-thiones.

INTRODUCTION
3,4-Dihydropyrimidine-2-thiones,1 as a core unit in most organic compounds, are chemical precursors of multifunctionalized pyrimidines in a broad range of medicinal agents. These complex heterocyclic scaffolds is assigned as one of the most fertile areas for both organic chemistry, medicinal chemistry and biochemistry, which display interesting pharmacological and biological properties such as calcium channel modulators, α1a-adrenergic receptor antagonists, mitotic kinesin inhibitors and hepatitis B virus replication inhibitors.2 Several marine alkaloids containing the pyrimidine core unit were found to show interesting biological activities such as antiviral, antibacterial and anti-inflammatory activity.3 Over the past decades, research interest in multifunctionalized pyrimidines, has surged rapidly, owing to the pharmacological properties associated with many derivatives of this privileged heterocyclic core.

Compounds containing the tetrazolo[1,5-a]pyrimidine scaffold have been reported to have more biological activities, there is considerable interest in the medicinal and biological applications of tetrazoles, such as antimicrobial activity,4 farnesyl transferase inhibitory,5 fungicidal activity,6 antihypertensive,7 KATP channel opening,8 central nervous system stimulating,9 etc.

However, after a detailed literature survey, we found that there were only limited publications devoted to the preparation of tetrazolopyrimidines. In general, these compounds were prepared by the multicomponent reaction between aminotetrazole, aldehyde and β-oxo carbonyl compounds or α, β-unsaturated carbonyl compounds using sulfamic acid,10-12 iodine,13 treating with HCl subsequently with p-toluenesulfonic acid,14 or in the absence of catalysis at 130-170 ºC,15 or using a base triethylamine in ethanol refluxing for 15 h.16 However, most of the synthetic protocols reported so far have some flaws, such as high temperatures, poor yields or prolonged reaction time

Recently, structures change associated with mercury-promoted desulfurization reactions, including hydrolysis, cyclizations and eliminations, have been reported.17-21 Because of the strong thiophilic affinity of Hg2+, mercuric acetate was used in the design of formation for HgS. We devised a strategy in which the azido group would be formed by desulfurization of 3,4-dihydropyrimidine-2-thiones using Hg2+ ion. The addition of the Hg2+ ion induced the N3- to attack the 2-C atom of pyrimidine, followed by the removal of HgS and the formation of intramolecular guanylation. Finally, a stable cyclic product tetrazolo[1,5-a]pyrimidine 2 was formed through an irreversible desulfurization reaction, as depicted in Scheme 1. To the best of our knowledge, elaboration of tetrazolo[1,5-a]pyrimidines through reactions of 3,4-dihydropyrimine-2-thiones with sodium azide was unprecedented. In the context of our interest in the synthesis of functionalized DHPM derivatives, we became interested in combining tetrazole with the DHPM core. In this paper, we would like to describe a general and comprehensive strategy for the preparation of ethyl 5-methyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylates and 6,6-dimethyl-9-aryl-5,6,7,9-tetrahydrotetrazolo[1,5-a]quinazolin-8(4H)-ones through direct cyclization reactions from 3,4-dihydropyrimidine-2(1H)-thiones and 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8- octahydroquinazoline-2-thiones with sodium azide.

RESULTS AND DISCUSSIONS

Initially, we chose the reaction of 3,4-dihydropyrimidine-2(1H)-thione 1a and sodium azide as a model reaction to optimize the reaction conditions. A series of experiments was performed to evaluate the feasibility of the formation of tetrazolo[1,5-a]pyrimidine and to identify the best cyclic agents. The results are shown in Table 1. By analogy with the mercury-promoted desulfurization reactions,17-21 the mixture of 1 equivalent of NaN3 and Hg(OAc)2 in acetic acid was heated at 100 ºC to give the cyclization product 2a in 56% yield (entry 6). It was found that Hg(OAc)2 and a stoichiometric amount of NaN3 are essential for the success of the reaction (entries 3-10) and 2 equivalent of NaN3 obtained the best result (entry 3). Another source of mercuric catalyst HgCl2 was used, but the reaction yield was slightly slower (entries 9-11). However, when using other catalysts Zn(OAc)2, ZnCl2, NiCl2, CoCl2, CuCl2, FeCl3, Cu(OAc)2, compound 2a was not detected by GC-Mass (or TLC), and starting DHPM 1a was recovered. After experimentation with different catalysts, solvents and reaction temperatures, it was found that the optimal proportion of the reaction between 3,4-dihydropyrimidine-2(1H)-thione 1a, sodium azide and mercuric acetate could be achieved 1: 2: 1 in acetic acid at 100 ºC within 6 h.

Under the optimized conditions, the substrate scope of the reaction was examined (Table 2). A variety dihydrotetrazolo[1,5-a]pyrimidines (2a-i) were regioselectively prepared through this method. The electronics of the aromatic groups of DHPMs did not appear to influence the process, as substrates substituted with methoxy or nitro groups gave comparable product yields. However, 3,4-dihydropyrimidine-2-thione with an o-nitro group on the phenyl ring do not give the desired product. We speculated that one possible reason is the big steric of nitro group.

Extension of the reaction to 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones 3 was successful, and compounds tetrahydrotetrazolo[1,5-a]quinazolines 4a-4h were obtained in good yields (Table 3). To our delight, further research suggested that the mercuric acetate catalyzed one-pot synthesis of tetrazolo[1,5-a]pyrimidines proceeded smoothly.

All the compounds were characterized by 1H NMR, 13C NMR, MS, and elemental analyses. The 1H NMR spectrum of product 2 and 4 exhibited a singlet around δ 6.7 as the C4-H, which confirmed the C2-N3 linked products tetrazolo[1,5-a]pyrimidines and tetrahydrotetrazolo[1,5-a]quinazolin-8(4H)-ones. According to previous study, when the methyl or N-allyl groups were in the N1 position, two cross peaks between the hydrogen atoms of the N-methyl or NCH2 groups of the allyl groups and C-2 and -6 were observed.22

The single crystal X-ray crystallography of product 2a also confirmed the structures of obtained products (Figure 1). Crystallographic data for the structure analysis have been deposited at the Cambridge Crystallographic Data Centre as supplementary publication (for 2a CCDC No. CCDC 807622).

In conclusion, we have developed a novel and efficient synthetic method to prepare ethyl 5-methyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylates and 6,6-dimethyl-9-aryl-5,6,7,9- tetrahydrotetrazolo[1,5-a]quinazolin-8(4H)-ones by the cyclization reactions between 3,4-dihydropyrimidine-2-thiones or 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline- 2-thiones, sodium azide and mercuric acetate. Compared to previously known approaches, the simplicity and higher efficiency make this method particularly attractive. These results provided, as well as other reported studies, this cyclization reaction conditions could be potentially applicable to other electron-deficient heterocylic or aromatic systems. The present study also provides a readily accessible approach to construct multifunctionalized pyrimidine template for diversity-oriented synthesis.

EXPERIMENTAL
Commercially available reagents were used without further purification. Solvents were treated prior to use according to the standard methods. Melting points were determined on an XT-4 electrothermal micromelting point apparatus and are uncorrected. NMR spectra were recorded at 400 (1H) and 100 (13C) MHz, respectively, on a Varian Mercury plus-400 instrument using CDCl3 and DMSO-d6 as solvent and TMS as an internal standard. Mass spectra were obtained on a Bruker Daltonics APEXII 47e FT-ICR spectrometer. The Biginelli 3,4-dihydropyrimidine-2-thiones 1 and 4-aryl-7,7-dimethyl-5-oxo- 1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones 3 were readily prepared according to the procedures reported.23,24

General procedure. The mixture of 3,4-dihydropyrimidine-2(1H)-thione (1 mmol), sodium azide (2 mmol) and mercuric acetate (1 mmol) in HOAc (5 mL) was stirred at 100 ºC for 6 h. After completion of the reaction (monitored by thin layer chromatography), the black sediment (HgS) was filtrated. Then water was added to the filtrate to give the crude product. It was recrystallization from EtOH to give the pure products 2 and 4.

2a: Yield 92%, mp 213-215 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.13 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.70 (s, 3H, 5-CH3), 4.05-4.14 (m, 2H, OCH2CH3), 6.73 (s, 1H, CH), 7.26-7.37 (m, 5H, ArH), 10.90 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.01, 19.54, 59.59, 60.51, 99.35, 127.30, 128.86, 128.97, 139.68, 145.92, 148.68, 164.85. Anal. Calcd for C14H15N5O2: C, 58.94; H, 5.30; N, 24.55. Found: C, 58.85; H, 5.23; N, 24.45. ESI-MS: m/z = 285 ([M + H+]).
2b: Yield 74%, mp 221-223 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.11 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.70 (s, 3H, 5-CH3), 4.03-4.09 (m, 2H, OCH2CH3), 7.19 (s, 1H, CH), 7.23-7.42 (m, 4H, ArH), 10.98 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 13.90, 19.49, 56.78, 60.51, 98.35, 127.41, 129.67, 130.18, 130.20, 133.41, 137.15, 146.65, 148.56, 164.60. Anal. Calcd for C14H14ClN5O2: C, 52.59; H, 4.41; N, 21.90. Found: C, 52.68; H, 4.49; N, 21.98. ESI-MS: m/z = 319 ([M + H+]).
2c: Yield 86%, mp 208-209 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.15 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.68 (s, 3H, 5-CH3), 3.78 (s, 3H, OCH3), 4.06-4.14 (m, 2H, OCH2CH3), 6.70 (s, 1H, 7-CH), 6.85 (d, J = 8 Hz, 2H, ArH), 7.29 (d, J = 8.8 Hz, 2H, ArH), 11.09 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.05, 19.48, 55.27, 59.08, 60.46, 99.46, 114.13, 128.57, 132.05, 145.68, 148.63, 159.90, 164.95. Anal. Calcd for C15H17N5O3: C, 57.13; H, 5.43; N, 22.21. Found: C, 57.05; H, 5.49; N, 22.30. ESI-MS: m/z = 315 ([M + H+]).
2d: Yield 85%, mp 250-252 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.08 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.71 (s, 6H, 2CH3), 4.01-4.08 (m, 2H, OCH2CH3), 6.98 (s, 1H, 7-CH), 7.12-7.26 (m, 4H, ArH), 11.25 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 13.90, 19.31, 19.40, 55.65, 60.39, 99.33, 126.75, 127.09, 128.80, 130.74, 136.09, 138.37, 146.16, 148.46, 164.85. Anal. Calcd for C15H17N5O2: C, 60.19; H, 5.72; N, 23.40. Found: C, 60.07; H, 5.78; N, 23.49. ESI-MS: m/z = 299 ([M + H+]).
2e: Yield 87%, mp 209-211 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.15 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.31 (s, 3H, CH3), 2.67 (s, 3H, CH3), 4.06-4.13 (m, 2H, OCH2CH3), 6.70 (s, 1H, 7-CH), 7.13 (d, J = 8 Hz, 2H, ArH), 7.24 (d, J = 7.6 Hz, 2H, ArH), 11.07 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.03, 19.46, 21.14, 59.33, 60.45, 99.41, 127.17, 129.39, 136.88, 138.82, 145.79, 148.71, 164.94. Anal. Calcd for C15H17N5O2: C, 60.19; H, 5.72; N, 23.40. Found: C, 60.07; H, 5.63; N, 23.52. ESI-MS: m/z = 299 ([M + H+]).
2f: Yield 79%, mp 244-246 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.15 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.69 (s, 3H, 5-CH3), 4.08-4.13 (m, 2H, OCH2CH3), 6.71 (s, 1H, CH), 7.27 (d, J = 8.8 Hz, 2H, ArH), 7.29 (d, J = 8.8 Hz, 2H, ArH), 11.22 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.04, 19.53, 58.94, 60.62, 98.87, 128.71, 129.09, 134.94, 138.17, 146.27, 148.61, 164.67. Anal. Calcd for C14H14ClN5O2: C, 52.59; H, 4.41; N, 21.90. Found: C, 52.65; H, 4.49; N, 21.98. ESI-MS: m/z = 319 ([M + H+]).
2g: Yield 73%, mp 225-227 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.16 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.73 (s, 3H, 5-CH3), 4.09-4.15 (m, 2H, OCH2CH3), 6.84 (s, 1H, 7-CH), 7.57 (d, J = 9.2 Hz, 2H, ArH), 8.22 (d, J = 8.4 Hz, 2H, ArH), 11.35 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.05, 19.70, 58.82, 60.88, 98.27, 124.17, 128.44, 146.04, 146.91, 148.10, 148.58, 164.39. Anal. Calcd for C14H14N6O4: C, 50.91; H, 4.27; N, 25.44. Found: C, 50.98; H, 4.18; N, 25.53. ESI-MS: m/z = 330 ([M + H+]).
2h: Yield 80%, mp 242-244 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.16 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.67 (s, 3H, 5-CH3), 4.06-4.13 (m, 2H, OCH2CH3), 6.69 (s, 1H, CH), 7.25 (d, J = 8.8 Hz, 2H, ArH), 7.47 (d, J = 8.8 Hz, 2H, ArH), 10.98 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.07, 19.56, 59.01, 60.65, 98.83, 123.15, 129.01, 132.07, 138.69, 146.24, 148.60, 164.67. Anal. Calcd for C14H14BrN5O2: C, 46.17; H, 3.87; N, 19.23. Found: C, 46.05; H, 3.80; N, 19.31. ESI-MS: m/z = 363 ([M + H+]).
2i: Yield 76%, mp 219-221 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.17 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.74 (s, 3H, 5-CH3), 4.09-4.15 (m, 2H, OCH2CH3), 6.85 (s, 1H, 7-CH), 7.57 (t, J = 8.8 Hz, 1H, ArH), 7.74 (d, J = 8 Hz, 1H, ArH), 8.20-8.22 (m, 2H, ArH), 11.28 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.05, 19.78, 58.96, 60.88, 98.35, 122.38, 124.03, 130.03, 133.53, 141.73, 146.92, 148.48, 148.58, 164.39. Anal. Calcd for C14H14N6O4: C, 50.91; H, 4.27; N, 25.44. Found: C, 50.99; H, 4.19; N, 25.51. ESI-MS: m/z = 330 ([M + H+]).
4a: Yield 76%, mp 326-327 ºC. 1H NMR (400 MHz, d6-DMSO/TMS): δ = 1.00 (s, 3H, CH3), 1.06 (s, 3H, CH3), 2.12-2.26 (m, 2H, CH2), 2.60 (s, 2H, CH2), 6.60 (s, 1H, 9-CH), 7.26-7.35 (m, 5H, ArH), 11.63 (s, 1H, NH). 13C NMR (100 MHz, d6-DMSO/TMS): δ = 26.99, 28.27, 32.32, 49.80, 57.44, 57.46, 105.65, 127.16, 128.34, 128.60, 140.46, 148.45, 150.50, 193.03. Anal. Calcd for C16H17N5O: C, 65.07; H, 5.80; N, 23.71. Found: C, 65.15; H, 5.73; N, 23.82. ESI-MS: m/z = 295 ([M + H+]).
4b: Yield 68%, mp 272-274 ºC. 1H NMR (400 MHz, d6-DMSO/TMS): δ = 1.00 (s, 3H, CH3), 1.06 (s, 3H, CH3), 2.12-2.25 (m, 2H, CH2), 2.60 (s, 2H, CH2), 6.63 (s, 1H, 9-CH), 7.33 (d, J = 8.4 Hz, 2H, ArH), 7.40 (d, J = 8.8 Hz, 2H, ArH), 11.67 (s, 1H, NH). 13C NMR (100 MHz, d6-DMSO/TMS): δ = 27.09, 28.15, 32.34, 49.77, 56.85, 105.28, 128.60, 129.19, 132.95, 139.41, 148.38, 150.68, 193.07. Anal. Calcd for C16H16ClN5O: C, 58.27; H, 4.89; N, 21.24. Found: C, 58.18; H, 4.94; N, 21.31. ESI-MS: m/z = 329 ([M + H+]).
4c: Yield 72%, mp 270-272 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.12 (s, 3H, CH3), 1.16 (s, 3H, CH3), 2.26-2.35 (m, 2H, CH2), 2.65-2.75 (m, 2H, CH2), 3.77 (s, 3H, OCH3), 6.70 (s, 1H, 9-CH), 6.84 (d, J = 8.8 Hz, 2H, ArH), 7.26 (d, J = 8.8 Hz, 2H, ArH), 11.36 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 27.56, 28.87, 32.88, 40.82, 50.50, 53.37, 57.77, 107.62, 114.09, 128.40, 131.57, 135.38, 148.79, 153.40, 193.74. Anal. Calcd for C17H19N5O2: C, 62.75; H, 5.89; N, 21.52. Found: C, 62.66; H, 5.83; N, 21.43. ESI-MS: m/z = 325 ([M + H+]).
4d: Yield 67%, mp 248-249 ºC. 1H NMR (400 MHz, d6-DMSO/TMS): δ = 0.99 (s, 3H, CH3), 1.06 (s, 3H, CH3), 2.12-2.26 (m, 2H, CH2), 2.61 (s, 2H, CH2), 6.78 (s, 1H, 9-CH), 7.62 (d, J = 8.8 Hz, 2H, ArH), 8.19 (d, J = 8.8 Hz, 2H, ArH), 11.78 (s, 1H, NH). 13C NMR (100 MHz, d6-DMSO/TMS): δ = 17.12, 18.05, 18.60, 22.33, 39.69, 46.90, 94.89, 113.69, 117.57, 118.80, 137.03, 138.41, 141.09, 183.04. Anal. Calcd for C16H16N6O3: C, 56.47; H, 4.74; N, 24.69. Found: C, 56.52; H, 4.79; N, 24.77. ESI-MS: m/z = 340 ([M + H+]).
4e: Yield 65%, mp 281-283 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.15 (s, 3H, CH3), 1.19 (s, 3H, CH3), 2.29-2.39 (m, 2H, CH2), 2.73-2.84 (m, 2H, CH2), 6.84 (s, 1H, 9-CH), 7.58 (t, J = 8 Hz, 1H, ArH), 7.84 (d, J = 8 Hz, 1H, ArH), 8.09-8.21(m, 2H, ArH), 11.49 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 27.62, 28.77, 33.04, 40.92, 50.35, 57.69, 106.46, 121.93, 124.04, 130.03, 133.95, 140.92, 148.57, 148.62, 149.83, 193.71. Anal. Calcd for C16H16N6O3: C, 56.47; H, 4.74; N, 24.69. Found: C, 56.56; H, 4.82; N, 24.75. ESI-MS: m/z = 340 ([M + H+]).
4f: Yield 70%, mp 296-298 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.06 (s, 3H, CH3), 1.15 (s, 3H, CH3), 2.21-2.32 (m, 2H, CH2), 2.63-2.72 (m, 2H, CH2), 3.67 (s, 3H, OCH3), 6.84 (s, 1H, 9-CH), 6.95-7.54 (m, 4H, ArH), 11.23 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 26.84, 29.09, 32.81, 40.91, 50.50, 55.36, 56.29, 106.40, 111.20, 120.68, 126.35, 130.38, 130.68, 149.45, 149.59, 157.22. 193.71. Anal. Calcd for C17H19N5O2: C, 62.75; H, 5.89; N, 21.52. Found: C, 62.68; H, 5.82; N, 21.63. ESI-MS: m/z = 325 ([M + H+]).
4g: Yield 69%, mp 326-328 ºC. 1H NMR (400 MHz, d6-DMSO/TMS): δ = 0.87 (s, 3H, CH3), 1.01 (s, 3H, CH3), 2.00-2.21 (m, 2H, CH2), 2.24-2.43 (m, 2H, CH2), 7.18 (d, J = 8.4 Hz, 2H, ArH), 7.52 (d, J = 8.4 Hz, 2H, ArH), 7.81 (s, 1H, 9-CH), 9.53 (s, 1H, NH). 13C NMR (100 MHz, d6-DMSO/TMS): δ = 26.83, 28.66, 32.26, 49.74, 51.53, 106.94, 128.47, 129.46, 131.19, 143.98, 151.69, 152.54, 192.85. Anal. Calcd for C16H16BrN5O: C, 51.35; H, 4.31; N, 18.71. Found: C, 51.28; H, 4.39; N, 18.63. ESI-MS: m/z = 373 ([M + H+]).
4h: Yield 71%, mp 304-305 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.12 (s, 3H, CH3), 1.16 (s, 3H, CH3), 2.30 (s, 3H, CH3), 2.31 (s, 2H, CH2), 2.67-2.78 (m, 2H, CH2), 6.71 (s, 1H, 9-CH), 7.13 (d, J = 8 Hz, 2H, ArH), 7.23 (d, J = 8 Hz, 2H, ArH), 11.47 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 21.15, 27.54, 28.84, 32.90, 40.80, 50.49, 58.03, 107.60, 127.02, 129.58, 136.34, 138.84, 148.80, 149.05, 193.75. Anal. Calcd for C17H19N5O: C, 66.00; H, 6.19; N, 22.64. Found: C, 66.12; H, 6.26; N, 22.71. ESI-MS: m/z = 309 ([M + H+]).

ACKNOWLEDGMENTS
We are thankful for the financial support from the National Nature Science Foundation of China (No. 20902073 and 21062017), the Natural Science Foundation of Gansu Province (No. 096RJZA116), and Scientific and Technological Innovation Engineering program of Northwest Normal University (nwnu-kjcxgc-03-64, nwnu-lkqn-10-15).

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