HETEROCYCLES

Paper | Regular issue | Vol. 81, No. 8, 2010, pp. 1843-1859
Received, 15th May, 2010, Accepted, 9th June, 2010, Published online, 10th June, 2010.
DOI: 10.3987/COM-10-11976

■ Novel Synthesis of 2-Alkoxy(Aralkoxy)-5-chloro[1,2,4]triazolo[1,5-a]quinazolines and Their Derivatives

Rashad Al-Salahi* and Detlef Geffken

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh-11451, Saudi Arabia

Abstract

2-Alkoxy(aralkoxy)-5-chloro[1,2,4]triazolo[1,5-a]quinazolines have been synthesized. The corresponding 2-alkoxy(aralkoxy)[1,2,4]triazolo[1,5-a]quinazolin-5-ones were chlorinated with either oxalyl chloride or phosphorus oxychloride. The chlorine atom at 5-position of the targeted [1,2,4]triazolo[1,5-a]quinazolines was replaced with multifunctional N-nucleophiles. This provided the preparation of the heterocyclic system bearing a variety of substituents at 5-position.

INTRODUCTION
We have already reported that, the alkylated derivatives of novel 2-alkoxy(aralkoxy)[1,2,4]triazolo[1,5-a]quinazolin-5-ones (I) have been proven as excellent agents for controlling the plant growth diseases caused by fungal pathogen.1 It has been demonstrated that subject of electron withdrawing atoms or groups in ring positions 5, 6 and 8 of the [1,2,3]triazolo[1,5-a]quinazolines (II) or [1,2,4]triazolo[3,4-a]phthalazines (III) enhances strongly the binding affinity towards benzodiazepine and adenosine A1, A2A receptors.2,3
This work has done in continuation of our program with the aim of obtaining an interesting series of chlorinated [1,2,4]triazolo[1,5-a]quinazoline compounds which was not only expected to be a valuable compound by further nucleophilic displacement reactions but also may contribute as a pharmacophore to the bioactivity of I.

RESULTS AND DISCUSSION
The synthetic strategy is outlined in Scheme 1. First, the 5-chloro[1,2,4]triazolo[1,5-a]quinazolines 2 required as our key starting materials were synthesized by chlorination of the corresponding I (previously prepared by condensation reaction of N-cyanoimidocarbonates with hydrazinobenzoic acid)4 with either oxalyl chloride in boiling 1,1,2-trichloroethane for 19 h or with phosphorus oxychloride in boiling benzene for 2 h, followed by trituration with a saturated aqueous solution of potassium carbonate.5 Although both methods gave acceptable yields, the reaction of I with phosphorus oxychloride is more advantageous with regard to short reaction time and higher yields (Table 1).
The formation of 2 was accompanied by the gradual disappearance of the characteristic (C=O) band of I at 1685-1705 cm-1. The structure of the novel 5-chloro[1,2,4]triazolo[1,5-a]quinazolines 2 was confirmed by IR, 1H NMR, 13C NMR spectra and microanalyses.
Hydrazinolysis of 2 in refluxing ethanol were formed the corresponding [1,2,4]triazolo[1,5-a]quinazolin-5-yl-hydrazines 3a-f in good yields of 60-78%,6 which upon treatment with equimolar amout of aldehyde or ketone furnished the targeted hydrazones 4a-d in 70-83%.7
Reaction of 3b,e with 1,1׳-carbonyldiimidazole in a molar ratio of 1:1.2 in boiling absolute toluene for 3 h provided the until hitherto unknown bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazolin-3-ones 5a,b in 45-50% yield.8 Similarly, the corresponding thioxo derivatives 6a,b could be obtained in 56-61% yield 9 from the reaction of 3e,f with carbon disulfide in a molar ratio of 1:10 in boiling pyridine for 2 h. The IR spectra of 5a,b display strong (C=O) absorption bands at 1705 and 1709 cm-1, and the 13C NMR spectra of 6a,b are characterized by a (C=S) resonance at 185.00 and 185.7 ppm.
Replacement of the chlorine in compounds 2 by different hydrazides occurred smoothly in refluxing toluene to produce the [1,2,4]triazoloquinazolin-5-yl-carbohydrazides 7a-e in 65-76% yield,10 which as themselves deserve interest as suitable intermediates and furthermore should open access to a number of triazolo-annelated compounds such as bis[1,2,4]triazoloquinazolines.
Analogously to the reaction with hydrazides, the corresponding reaction of compounds 2 with carbazates according to literature10 produced the respective [1,2,4]triazoloquinazolin-5-yl-hydrazine carboxylic acid esters of type 8a-d in 73-80 % yield as colorless solids.
The IR spectra of 7a-f are characterized by a strong (C=O) absorption band at 1660-1670 and a weak (NH) band at 3189-3210 cm-1 respectively, while compounds 8a-d display a strong (C=O) absorption band at 1706-1718 and a weak (NH) absorption band at 3198-3261 cm-1.

After having successfully elaborated the synthesis of the carbohydrazides 7a-f, our interest arose wether these compounds could be cyclo-condensed to the novel bis[1,2,4]triazoloquinazolines of type 11. Actually, when 2a,b,f were treated with acylhydrazines in a molar ratio of 1:2 in absolute toluene, the primarily formed acylamidrazones 9 (Scheme 2) underwent smoothly a base-catalyzed cyclization to provide the corresponding bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazolines 11.10 This approach proved to be successful for the preparation of 11a-c (Table 2) but failed in the case of 11d-f. Therefore, the amidrazones 7b,c,d were treated with phosphorus oxychloride at refluxing temperature for 2 h to furnish the respective intermediates 10, which upon subsequent neutralization with saturated aqueous potassium carbonate solution or aqueous ammonia delivered the targeted 11d-f.11 The completion of the internal cyclization was monitored by IR spectroscopy: disappearence of the (C=O) and (NH) absorption bands at 1650-1670, 3173-3194 cm-1 signaled complete conversion of 9 or 10 to the tetracyclic compounds 11. In addition, the structure of compound 11b has been unambiguously proven by X-ray crystallography (Figure 1).

Treatment of 5-chloro[1,2,4]triazoloquinazolines 2a,b,e,f with sodium azide in a molar ratio of 1:1.2 in absolute dimethyl formamide for 24 h at 90 oC, furnished the aimed tetrazolo[4,3-c][1,2,4]triazolo[1,5-a]quinazolines 13a-d via the (not isolated) intermediates 12 as colorless solids in 51-60% yield12 (Scheme 3). Furthermore, treatment of 3 with nitrous acid at -5 oC for 30-40 min afforded also the tetrazole products 13 in 53-58% yield.10 The beforementioned facile nucleophilic displacement of the chlorine atom in 2 prompted us to investigate the reaction of 2 with methyl 3-aminothiophene-2-carboxylate, which theoretically should provide access to the novel pentacyclic compounds of type 15. In fact, when 2d,e were reacted with methyl 3-aminothiophene-2-carboxylate in absolute dioxane in a molar ratio of 1:1.6, followed by addition of sodium hydride, the targeted 15a,b could be isolated from the reaction mixture in 69 and 81% yield (Scheme 3).10 The IR spectra of compounds 15a,b are characterized by a (C=O) stretching at 1670 and 1667 cm-1 respectively.
In conclusion, replacement of the chlorine atom in the targeted compounds by different nucleophiles has been achieved successfully and provided access to a series of tetracyclic, pentacyclic systems and a variety of open chained derivatives.

EXPERIMENTAL
Melting points were determined on open glass capillaries using a Mettler FP 62 apparatus and are uncorrected. Elemental analyses were carried out with a Heraeus CHN-O-Rapid Instrument. The IR (KBr) spectra were recorded on a Shimadzu FT-IR 8300. 1H-NMR (400.1 MHz) and 13C-NMR spectra were recorded on a Bruker AMX 400 spectrometer and chemical shifts are giving in a (ppm) downfield from tetramethylsilane (TMS) as an internal standard, DMSO is using as solvent. Mass spectra were recorded on a Finnigan MAT 311A and on a VG 70-250S (VG Analytical) instrument. Follow up of the reactions and checking the purity of compounds was made by TLC on DC-Mikrokarten polygram SIL G/UV254, from the Macherey-Nagel Firm, Duren Thickness: 0.25 m. Column chromatography was conducted on silica gel (ICN Silica 100-200, active 60 Å).
General procedure for the synthesis of 2-Alkoxy(aralkoxy)-5-chloro[1,2,4]triazolo[1,5-a]quinazolines (2a-f).
Method A: Compound I (2 mmol) was heated with oxalyl chloride (6 mmol) in 1,1,2-trichloroethane (12 mL) for 19 h at 105 oC. The solution was cooled and MeOH (0.2 mL) was added dropwise. The obtained solid was filtered, washed with hexane, dried and recrystallized from THF-hexane.
Method B: Compound I (1 mmol) was heated with POCl3 (1 mL) in benzene (7 mL) for 2 h. The solvent was evaporated and the residue was treated with saturated aqueous solution of potassium carbonate. The solid was filtered, washed thoroughly with water, dried and recrystallized from THF-hexane.
5-Chloro-2-methoxy[1,2,4]triazolo[1,5-a]quinazoline (2a): This compound obtained as white solid with 0.187 g (80%). mp 146-148 oC; 1H-NMR (400 MHz, DMSO-d6): δ 3.99 (s, 3H), 7.48-8.15 (m, 4H); 13C-NMR (100 MHz, DMSO-d6): δ 57.16, 114.20, 116.83, 125.51, 128.57, 135.74, 136.19, 141.11, 159.90, 168.26; MS m/z: (234)+; Anal. Calcd for C10H7ClN4O (234.65): C 51.19, H 3.01, N 23.88. Found: C 51.12, H 3.18, N 23.98.
5-Chloro-2-ethoxy[1,2,4]triazolo[1,5-a]quinazoline (2b): This compound obtained as white solid with 89% (0.220 g). mp 131-134 oC; 1H-NMR (400 MHz, DMSO-d6): δ 1.37 (t, 3H, J = 7.07 Hz), 4.34 (q, 2H, J = 14.13 Hz), 7.49-8.15 (m, 4H); 13C-NMR (100 MHz, DMSO-d6): δ 14.83, 65.67, 114.17, 116.75, 125.52, 128.80, 135.18, 136.13, 142.20, 159.92, 167.38; MS m/z: (248)+; Anal. Calcd for C11H9ClN4O (248.67): C 53.13, H 3.65, N 22.53. Found: C 53.33, H 3.98, N 22.33.
2-Allyloxy-5-chloro[1,2,4]triazolo[1,5-a]quinazoline (2c): This compound obtained as yellow solid with 0.226 g (87%). mp 113-115 oC; 1H-NMR (400 MHz, DMSO-d6): δ 4.86 (d, 2H, J = 6.53 Hz), 5.42-5.65 (m, 2H), 6.15-6.20 (m, 1H), 7.48-8.04 (m, 4H); 13C-NMR (DMSO-d6): δ 70.32, 115.17, 117.44, 118.80, 127.13, 128.17, 134.10, 135.30, 135.62, 137.19, 159.11, 167.90; MS m/z: (260)+; Anal. Calcd for C12H9ClN4O (260.68): C 55.29, H 3.48, N 21.49. Found: C 54.94, H 3.67, N 21.09.
5-Chloro-2-pentyloxy[1,2,4]triazolo[1,5-a]quinazoline (2d): This compound obtained as pale brown solid with 0.234 g (81%). mp 108-110 oC; 1H-NMR (400 MHz, DMSO-d6): δ 0.96 (t, 3H, J = 7.45 Hz), 1.37-1.47 (m, 4H), 1.83-1.89 (m, 2H), 4.43 (t, 2H, J = 7.60 Hz), 7.45-8.16 (m, 4H); 13C-NMR (100 MHz, DMSO-d6): δ 13.75, 21.70, 27.35, 28.16, 69.52, 114.70, 116.81, 126.54, 127.95, 135.57, 136.63, 155.33, 166.57; MS m/z: (290)+; Anal. Calcd for C14H15ClN4O (290.75): C 57.83, H 5.20, N 19.27. Found: C 57.93, H 5.29, N 18.98.
2-Benzyloxy-5-chloro[1,2,4]triazolo[1,5-a]quinazoline (2e): This compound obtained as white solid with 0.279 g (90%). mp 128-130 oC; 1H-NMR (400 MHz, DMSO-d6): δ 5.79 (s, 2H), 7.37-8.45 (m, 9H), 13C-NMR (100 MHz, DMSO-d6): δ 71.34, 115.20, 117.42, 125.50, 126.71, 127.14, 128.07, 128.70, 132.41, 135.90, 136.11, 136.77, 155.93, 165.25; MS m/z: (310)+; Anal. Calcd for C16H11ClN4O (310.75): C 61.84, H 3.57, N 18.03. Found: C 61.80, H 3.82, N 17.88.
5-Chloro-2-phenethyloxy[1,2,4]triazolo[1,5-a]quinazoline (2f): This compound obtained as white solid with 0.294 g (91%). mp 137-140 oC; 1H-NMR (400 MHz, DMSO-d6): δ 3.15 (t, 2H, J = 7.50 Hz), 4.65 (t, 2H, J = 7.51 Hz), 7.22-8.37 (m, 9H); 13C-NMR (100 MHz, DMSO-d6): δ 35.09, 69.61, 114.59, 124.40, 124.83, 126.72, 128.74, 129.30, 134.29, 134.94, 138.49, 153.37, 156.84, 168.61; MS m/z: (324)+; Anal. Calcd for C17H13ClN4O (324.77): C 62.87, H 4.03, N 17.25. Found: C 62.57, H 4.22, N 17.15.
General procedure for the synthesis of 2-Alkoxy(aralkoxy)[1,2,4]triazolo[1,5-a]quinazolin-5-yl-hydrazines (3a-f): Compound 2 (1 mmol) was heated under reflux with hydrazine hydrate (5 mmol) in EtOH (8 mL) for 3 h. After cooling, the precipitate was filtered off and washed with water. Recrystallization from EtOH afforded 3a-f as colored pure solids.
2-Methoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl-hydrazine (3a): This compound obtained as white solid with 0.138 g (60%). mp 233-235 oC; IR (KBr) ν max cm-1: 3205, 3250; 1H-NMR (400 MHz, DMSO-d6): δ 3.98 (s, 3H), 4.94 (s, 2H), 7.47-8.30 (m, 4H), 9.37 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 56.48, 114.48, 124.40, 124.77, 125.40, 127.35, 134.24, 134.98, 153.51, 169.23; MS m/z: (230)+; Anal. Calcd for C10H10N6O (230.23): C 52.17, H 4.38, N 36.50. Found: C 52.46, H 4.25, N 36.15.
2-Ethoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl-hydrazine (3b): This compound obtained as white solid with 0.168 g (69%). mp 215-218 oC; IR (KBr) ν max cm-1: 3189, 3231; 1H-NMR (400 MHz, DMSO-d6): δ 1.30 (t, 3H, J = 7.07 Hz), 4,37 (q, 2H, J = 14.13 Hz), 4.65 (s, 2H), 7.49-8.15 (m, 4H), 9.42 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 14.73, 65.61, 114.12, 116.45, 125.62, 128.43, 135.13, 136.29, 142.38, 159.82, 167.92; MS m/z: (244)+; Anal. Calcd for C11H12N6O (244.26): C 54.09, H 4.95, N 34.41. Found: C 54.37, H 5.12, N 34.27.
2-Allyloxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl-hydrazine (3c): This compound obtained as yellow solid with 0.181 g (71%). mp 220-223 oC; IR (KBr) ν max cm-1: 3210, 3267; 1H-NMR (400 MHz, DMSO-d6): δ 4.81 (s, 2H), 4.85 (d, 2H, J = 5.30 Hz), 5.29-5.43 (m, 2H), 6.06-6.12 (m, 1H) 7.47-8.30 (m, 4H), 9.90 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 69.53, 70.55, 113.12, 114.59, 118.32, 124.41, 133.52, 134.26, 134.95, 150.72, 161.12, 168.50; MS m/z: (256)+; Anal. Calcd for C12H12N6O (256.27): C 56.24, H 4.72, N 32.79. Found: C 56.50, H 4.54, N 32.93.
2-Pentyloxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl-hydrazine (3d): This compound obtained as white solid with 0.177 g (62%). mp 197-200 oC; IR (KBr) ν max cm-1: 3183, 3256; 1H-NMR (400 MHz, DMSO-d6): δ 0.94 (t, 3H, J = 7.40 Hz), 1.34-1.44 (m, 4H), 1.71-1.77 (m, 2H), 4.35 (t, 2H, J = 7.60 Hz), 4.93 (s, 2H), 7.55-8.17 (m, 4H ), 9.98 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 14.23, 22.18, 27.89, 28.63, 69.05, 114.2, 124.41, 124.55, 124.70, 134.20, 134.99, 147.72, 153.90, 167.74; MS m/z: (286)+; Anal. Calcd for C14H18N6O (286.34): C 58.73, H 6.34, N 29.35. Found: C 59.21, H 6.02, N 29.28.
2-Benzyloxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl-hydrazine (3e): This compound obtained as white solid with 0.238 g (78%). mp 213-215 oC; IR (KBr) ν max cm-1: 3209, 3286; 1H-NMR (400 MHz, DMSO-d6): δ 4.82 (s, 2H), 5.40 (s, 2H), 7.33-8.32 (m, 9H), 9.91 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 69.63, 113.85, 116.43, 118.20, 125.12, 128.15, 132.62, 135.30, 135.66, 147.34, 159.45, 166.93; MS m/z: (306)+; Anal. Calcd for C16H14N6O (306.33): C 62.74, H 4.61, N 27.43. Found: C 62.54, H 4.43, N 27.24.
2-Phenethyloxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl-hydrazine (3f): This compound obtained as yellow solid with 0.230 g (72%). mp 187-190 oC; IR (KBr) ν max cm-1: 3217, 3280; 1H-NMR (400 MHz, DMSO-d6): δ 3.40 (t, 2H, J = 7.70 Hz), 4.62 (t, 2H, J = 7.45 Hz), 4.95 (s, 2H), 7.20-8.24 (m, 9H), 9.94 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 34.66, 69.13, 109.89, 114.12, 125.51, 126.8, 128.59, 128.74, 133.76, 134.75, 136.15, 138.30, 152.94, 156.35, 168.18; MS m/z: (320)+; Anal. Calcd for C17H16N6O (320.36): C 63.74, H 5.03, N 26.23. Found: C 63.47, H 4.94, N 26.43.
General procedure for the synthesis of N-Alkylidene-N'-(2-alkoxy(aralkoxy)[1,2,4]triazolo[1,5-a]quinazolin-5-yl)hydrazine (4a-e):
A mixture of 3a,e,f (1 mmol) and aldehyde or ketone (1 mmol) was refluxed in EtOH (10 mL) for 3 h. The solvent was removed under reduced pressure, and the resulting solids were recrystallized from EtOH.
N-Isopropylidene-N'-(2-methoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)hydrazine (4a): This compound obtained as yellow solid with 0.189 g (70 %). mp 186-189 oC; 1H-NMR (400 MHz, DMSO-d6): δ 2.21 (s, 3H), 2.63 (s, 3H), 2.85 (s, 3H), 7.37-8.54 (m, 4H), 10.45 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 13.80, 18.67, 25.27, 115.08, 124.90, 125.75, 126.06, 134.24, 134.96, 163.37, 164.54; MS m/z: (270)+; Anal. Calcd for C13H14N6O (270.30): C 57.77, H 5.22, N 31.09. Found: C 57.52, H 4.94, N 31.42.
N'-(2-Benzyloxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)-N-isopropylidene-hydrazine (4b): This compound obtained as yellow solid with 0.252 g (73%). mp 195-198 oC; 1H-NMR (400 MHz, DMSO-d6): δ 2.12 (s, 3H), 2.30 (s, 3H), 5.54 (s, 2H), 6.34 (s, 1H), 7.37-8.63 (m, 9H); 13C-NMR (100 MHz, DMSO-d6): δ 12.71, 13.43, 70.88, 103.16, 109.37, 114.05, 121.53, 124.69, 128.18, 128.46, 136.08, 136.74, 143.30, 150.85, 152.63, 169.21; MS m/z: (346)+; Anal. Calcd for C19H18N6O (346.39): C 65.88, H 5.24, N 24.26. Found: C 65.73, H 4.98, N 24.31.
N-Benzylidene-N'-(2-phenethyloxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)hydrazine (4c): This compound obtained as yellow solid with 0.322 g (79%). mp 215-218 oC; 1H-NMR (400 MHz, DMSO-d6): δ 3.12 (t, 2H, J = 7.34 Hz), 3.33 (s, 1H), 4.57 (t, 2H, J = 7.23 Hz), 7.25-8.55 (m, 14H), 11.83 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 35.11, 69.79, 110.23, 114.12, 115.37, 124.65, 126.43, 127.54, 128.61, 129.20, 130.11, 131.58, 132.27, 135.78, 139.52, 141.32, 154.20, 168.97; MS m/z: (408)+; Anal. Calcd for C24H20N6O (408.47): C 70.57, H 4.94, N 20.57. Found: C 70.29, H 5.14, N 20.41.
N'-(2-Phenethyloxy)[1,2,4]triazolo[1,5-a]quinazolin-5-yl)-N-(1-phenylethylidene)hydrazine (4d): This compound obtained as yellow solid with 0.286 g (68%). mp 198-203 oC; 1H-NMR (400 MHz, DMSO-d6): δ 2.87 (s, 3H), 3.43 (t, 2H, J = 7.74 Hz), 4.77 (t, 2H, J = 7.83 Hz), 7.25-8.55 (m, 14H), 9.91 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 14.65, 35.10, 69.79, 110.73, 114.62, 116.73, 124.65, 125.33, 126.23, 128.11, 129.20, 131.11, 131.58, 132.27, 135.78, 139.52, 141.32, 145.34, 152.20, 161.57; MS m/z: (422)+; Anal. Calcd for C25H22N6O (422.49): C 71.07, H 5.25, N 19.89. Found: C 70.81, H 5.01, N 20.28.
General procedure for the synthesis of 2-Alkoxy(aralkoxy)-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazolin-3-ones (5a,b): A mixture of 3b,e (0.5 mmol) and 1,1`-carbonyldiimidazole (0.6 mmol) was refluxed in absolute toluene (7 mL) for 3 h. The solvent was removed under reduced pressure and the residue was treated with CHCl3. The resulting solid was separated by filtration and recrystallized from EtOH.
2-Ethoxy-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazolin-3-one (5a): This compound obtained as white solid with 0.61 g (45%). mp 208-211 oC; IR (KBr) ν max cm-1: 1709 ; 1H-NMR (400 MHz, DMSO-d6): δ 1.47 (t, 3H, J = 7.24 Hz), 4.14 (q, 2H, J = 13.77 Hz), 7.31-7.92 (m, 4H), 12.24 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 13.73, 66.15, 114.63, 116.43, 125.12, 127.64, 135.66, 136.76, 147.73, 157.43, 168.37; MS m/z: (270)+; Anal. Calcd for C12H10N6O2 (270.25): C 53.33, H 3.73, N 31.10. Found: C 53.68, H 4.02, N 30.89.
2-Benzyloxy-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazolin-3-one (5b): This compound obtained as yellow solid with 0.83 g (50%). mp 203-206 oC; IR (KBr) ν max cm-1: 1705; 1H-NMR (400 MHz, DMSO-d6): δ 5.41 (s, 2H), 7.28-8.22 (m, 9H), 12.87 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 70.53, 110.38, 114.59, 120.67, 124.87, 128.48, 133.33, 134.30, 134.89, 136.89, 147.67, 153.38, 156.80, 168.62; MS m/z: (332)+; Anal. Calcd for C17H12N6O2 (332.32): C 61.44, H 3.64, N 25.29. Found: C 61.58, H 3.40, N 25.42.
General procedure for the synthesis of 2-Aralkoxy-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazolin-3-thiones (6a,b): A mixture of 3e,f (0.5 mmol) and CS2 (2.5 mmol) in pyridine (5 mL) was refluxed for 2 h. After cooling, the mixture was poured into ice/water, the yellow precipitate was filtered off, washed with water and recrystallized from MeOH.
2-Benzyloxy-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazolin-3-thione (6a): This compound obtained as yellow solid with 0.106 g (61%). mp 228-230 oC; 1H-NMR (400 MHz, DMSO-d6): δ 5.48 (s, 2H), 7.38-822 (m, 9H), 14.60 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 71.52, 112.05, 115.19, 124.16, 125.63, 126.87, 128.74, 128.83, 133.33, 134.42, 136.15, 142.06, 157.12, 163.17, 185.67; MS m/z: (348)+; Anal. Calcd for C17H12N6OS (348.39): C 58.61, H 3.47, N 24.12, S 9.20. Found: C 58.37, H 3.42, N 24.43, S 8.93.
2-Phenethyloxy-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazolin-3-thione (6b): This compound obtained as yellow solid with 0.102 g (56%). mp 192-195 oC; 1H-NMR (400 MHz, DMSO-d6): δ 3.25 (t, 2H, J = 7.82 Hz), 4.76 (t, 2H, J = 7.65 Hz), 7.10-8.45 (m, 9H), 14.54 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 34.45, 69.99, 114.23, 122.43, 125.83, 126.32, 128.28, 128.85, 131.75, 132.38, 135.86, 137.80, 145.64, 167.35, 184.98; MS m/z: (362)+; Anal. Calcd for C18H14N6OS (362.42): C 59.66, H 3.89, N 23.19, S 8.85. Found: C 60.04, H 3.95, N 23.02, S 8.53.
General procedure for the synthesis of N-(2-Alkoxy(aralkoxy)[1,2,4]triazolo[1,5-a]quinazolin-5-yl)-carbohydrazides (7a-f): A mixture of 2a,b,e (1 mmol) and the corresponding carbohydrazide (2.2 mmol) was refluxed in toluene (10 mL) for 2.5 h. After cooling, the solid was collected by filtration. Analytically pure products 7a-f were obtained by recrystallization from MeOH.
N-(2-Methoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)acetohydrazide (7a): This compound obtained as white solid with 0.182 g (67%). mp 208-210 oC; IR (KBr) ν max cm-1: 1669, 3206; 1H-NMR (400 MHz, DMSO-d6): δ 2.02 (s, 3H), 4.00 (s, 3H), 7.58-8.42 (m, 4H), 10.17 (s, 1H), 10.31 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 12.07, 61.22, 109.71, 114.80, 124.06, 125.14, 134.98, 135.34, 152.81, 156.69, 166.23, 169.46; MS m/z: (272)+; Anal. Calcd for C12H12N6O2 (272.27): C 52.94, H 4.44, N 30.87. Found: C 52.71, H 4.31, N 30.69.
N-(2-Methoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)benzohydrazide (7b): This compound obtained as white solid with 0.237 g (71%). mp 178-180 oC; IR (KBr) ν max cm-1: 1665, 3193; 1H-NMR (400 MHz, DMSO-d6): δ 3.98 (s, 3H), 7.53-8.51 (m, 9H), 10.52 (s, 1H), 10.81 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 56.67, 109.83, 114.88, 124.93, 125.29, 127.81, 127.99, 128.87, 129.07, 132.21, 132.81, 133.04, 135.09, 157.07, 169.44; MS m/z: (334)+; Anal. Calcd for C17H14N6O2 (334.34): C 61.07, H 4.22, N 25.14. Found: C 61.35, H 4.34, N 24.90.
N-(2-Methoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)isonicotinichydrazide (7c): This compound obtained as white solid with 0.217 g (65%). mp 147-150 oC; IR (KBr) ν max cm-1: 1668, 3210; 1H-NMR (400 MHz, DMSO-d6): δ 3.98 (s, 3H), 7.65-8.50 (m, 8H), 10.66 (s, 1H), 11.14 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 65.69, 109.73, 114.94, 121.73, 124.88, 125.36, 128.45, 133.20, 135.21, 139.74, 150.94, 152.66, 155.50, 164.82; MS m/z: (335)+; Anal. Calcd for C16H13N7O2 (335.33): C 57.31, H 3.91, N 29.24. Found: C 57.57, H 3.73, N 28.93.
N-(2-Ethoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)benzohydrazide (7d): This compound obtained as white solid with 0.236 g (68%). mp 160-164 oC; IR (KBr) ν max cm-1: 1660, 3189; 1H-NMR (400 MHz, DMSO-d6): δ 1.36 (t, 3H, J = 7.20 Hz), 4.35 (q, 2H, J = 13.99 Hz), 7.53-8.51 (m, 9H), 10.57 (s, 1H), 10.81 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 14.94, 65.16, 109.83, 114.88, 124.94, 125.26, 127.96, 128.96, 132.42, 132.81, 135.09, 135.36, 152.60, 157.04, 166.39, 168.73; MS m/z: (348)+; Anal. Calcd for C18H16N6O2 (348.37): C 62.06, H 4.63, N 24.12. Found: C 62.30, H 4.52, N 23.95.
N-(2-Ethoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)isonicotinichydrazide (7e): This compound obtained as white solid with 0.244 g (70%). mp 170-173 oC; IR (KBr) ν max cm-1: 1664, 3206; 1H-NMR (400 MHz, DMSO-d6): δ 1.35 (t, 3H, J = 7.50 Hz), 4.38 (q, 2H, J = 14.04 Hz), 7.51-8.48 (m, 8H), 10.42 (s, 1H), 10.91 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 14.46, 64.80, 109.30, 114.45, 122.18, 122.70, 124.92, 134.79, 147.91, 148.92, 156.25, 163.54, 168.03; MS m/z: (349)+; Anal. Calcd for C17H15N7O2 (349.35): C 58.45, H 4.33, N 28.07. Found: C 58.61, H 4.22, N 28.35.
N-(2-Benzyloxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)acetohydrazide (7f): This compound obtained as yellow solid with 0.264 g (76%). mp 189-192 oC; IR (KBr) ν max cm-1: 1670, 3197; 1H-NMR (400 MHz, DMSO-d6): δ 2.27 (s, 3H), 5.66 (s, 2H), 7.59-8.76 (m, 9H), 10.48 (s, 1H), 10.59 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 12.09, 71.67, 114.88, 115.24, 124.78, 125.21, 127.67, 128.46, 128.80, 131.16, 135.60, 136.06, 137.08, 156.68, 168.72, 169.22; MS m/z: (348)+; Anal. Calcd for C18H16N6O2 (348.37): C 62.06, H 4.63, N 24.12. Found: C 62.44, H 4.51, N 24.21.
General procedure for the synthesis of Alkyl(aralkyl)-N-(2-alkoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)hydrazine carboxylate (8a-d): A mixture of 2a,b (1 mmol) and benzyl carbazate or ethyl carbazate (2.2 mmol) was refluxed in benzene (10 mL) for 2.5 h. The solvent was removed under reduced pressure, the resulting solid was filtered off and recrystallized from MeOH.
Ethyl-N-(2-methoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)hydrazine carboxylate (8a): This compound obtained as white solid with 0.220 g (73%). mp 127-130 oC; IR (KBr) ν max cm-1: 1707, 3198; 1H-NMR (400 MHz, DMSO-d6): δ 1.23 (t, 3H, J = 7.91 Hz), 4.00 (q, 2H, J = 10.12 Hz), 4.10 (s, 3H), 7.59-8.27 (m, 4H), 9.50 (s, 1H), 10.34 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 14.92, 57.33, 61.15, 109.71, 114.83, 124.75, 125.21, 127.07, 134.70, 135.06, 137.15, 156.69, 169.23; MS m/z: (302)+; Anal. Calcd for C13H14N6O3 (302.29): C 51.65, H 4.67, N 27.80. Found: C 51.93, H 4.55, N 27.64.
Benzyl-N-(2-methoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)hydrazine carboxylate (8b): This compound obtained as white solid with 0.273 g (75%). mp 197-200 oC; IR (KBr) ν max cm-1: 1718, 3215; 1H-NMR (400 MHz, DMSO-d6): δ 4.01 (s, 3H), 5.15 (s, 2H), 7.20-8.41 (m, 9H), 9.68 (s, 1H), 10.40 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 56.69, 66.98, 109.67, 114.85, 124.75, 125.25, 126.25, 128.54, 128.81, 135.11, 135.33, 136.98, 152.74, 157.10, 168.42; MS m/z: (364)+; Anal. Calcd for C18H16N6O3 (364.37): C 59.34, H 4.43, N 23.06. Found: C 59.16, H 4.33, N 22.85.
Ethyl-N-(2-ethoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)hydrazine carboxylate (8c): This compound obtained as white solid with 0.233 g (74%). mp 165-167 oC; IR (KBr) ν max cm-1: 1710, 3261; 1H-NMR (400 MHz, DMSO-d6): δ 1.30 (t, 3H, J = 7.75 Hz), 1.73 (t, 3H, J = 7.89 Hz), 4.20 (q, 2H, J = 14.04 Hz), 4.65 (q, 2H, J = 14.06 Hz), 7.50-8.40 (m, 4H), 9.89 (s, 1H), 10.54 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 14.70, 14.96, 61.15, 65.12, 114.84, 124.71, 125.18, 127.24, 128.11, 129.34, 131.87, 135.05, 151.12, 167.32; MS m/z: (316)+; Anal. Calcd for C14H16N6O3 (316.32): C 53.16, H 5.10, N 26.57. Found: C 53.56, H 4.96, N 26.41.
Benzyl-N-(2-ethoxy[1,2,4]triazolo[1,5-a]quinazolin-5-yl)hydrazine-carboxylate (8d): This compound obtained as white solid with 0.302 g (80%). mp 119-122 oC; IR (KBr) ν max cm-1: 1706, 3215; 1H-NMR (400 MHz, DMSO-d6): δ 1.39 (t, 3H, J = 7.30 Hz), 4.40 (q, 2H, J = 14.20 Hz), 5.20 (s, 2H), 7.19-8.39 (m, 9H), 9.69 (s, 1H), 10.37 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 14.97, 65.16, 66.45, 109.66, 114.85, 124.71, 125.19, 128.08, 128.79, 135.07, 135.33, 136.99, 152.62, 156.90; MS m/z: (378)+; Anal. Calcd for C19H18N6O3 (378.39): C 60.31, H 4.79, N 22.21. Found: C 60.04, H 4.90, N 22.21.
General procedure for the synthesis of 2-Alkoxy(aralkoxy)-3-alkyl-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazolines (11a-c): A mixture of 2b,f (1 mmol) and formohydrazide or acetohydrazide (2.2 mmol) was refluxed in absolute toluene (15 mL) in the presence of sodium hydride (0.8 mmol) for 14-20 h. The solvent was removed under reduced pressure, and the residue was crystallized from MeOH.
2-Ethoxy-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazoline (11a): This compound obtained as yellow solid with 0.127 g (50%). mp 192-195 oC; 1H-NMR (400 MHz, DMSO-d6): δ 1.48 (t, 3H, J = 7.75 Hz), 4.48 (q, 2H, J = 14.12 Hz), 7.65-8.30 (m, 4H), 9.90 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 14.84, 66.37, 111.71, 115.18, 123.57, 124.77, 126.99, 134.34, 137.50, 142.17, 152.17, 164.25; MS m/z: (254)+; Anal. Calcd for C12H10N6O (254.25): C 56.69, H 3.96, N 33.05. Found: C 57.11, H 4.17, N 33.30.
2-Ethoxy-3-methyl-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazoline (11b): This compound obtained as yellow solid with 0.147 g (55%). mp 203-205 oC; 1H-NMR (400 MHz, DMSO-d6): δ 1.43 (t, 3H, J = 7.49 Hz), 2.89 (s, 3H), 4.46 (q, 2H, J = 14.97 Hz), 7.62-8.42 (m, 4H); 13C-NMR (100 MHz, DMSO-d6): δ 12.10, 14.70, 66.29, 111.99, 115.16, 124.38, 126.94, 131.07, 132.61, 146.83, 151.12, 162.17; MS m/z: (268)+; Anal. Calcd for C13H12N6O (268.28): C 58.20, H 4.51, N 31.33. Found: C 58.87, H 4.40, N 31.49.
2-Phenethyloxy-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazoline (11c): This compound obtained as yellow solid with 0.168 g (51%). mp 226-228 oC; 1H-NMR (400 MHz, DMSO-d6): δ 3.15 (t, 2H, J = 7.23 Hz), 4.64 (t, 2H, J = 7.13 Hz), 7.25-8.50 (m, 9H), 9.68 (s, 1H); 13C-NMR (100 MHz, DMSO-d6): δ 35.05, 69.43, 112.73, 119.68, 124.58, 126.79, 128.71, 129.27, 134.10, 138.51, 154.98, 167.32; MS m/z: (330)+; Anal. Calcd for C18H14N6O (330.35): C 65.45, H 4.27, N 25.44. Found: C 65.96, H 3.98, N 25.25.
General procedure for the synthesis of 2-Alkoxy(aralkoxy)-3-aryl-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazolines (11d-f): A mixture of 7b,c,d ( 0.5 mmol) and POCl3 (5 mL) was refluxed at 100 oC for 2 h. After cooling, the excess of POCl3 was removed under reduced pressure and the residue was treated with saturated aqueous solution of K2CO3 under ice cooling. The resulting solids were collected by filtration and recrystallized from MeOH to afford 9d-f as colored pure products.
2-Ethoxy-3-phenyl-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazoline (11d): This compound obtained as yellow solid with 0.224 g (68%). mp 222-225 oC; 1H-NMR (400 MHz, DMSO-d6): δ 1.68 (t, 3H, J = 7.85 Hz), 4.58 (q, 2H, J =13.98 Hz), 7.65-8.81 (m, 9H); 13C-NMR (100 MHz, DMSO-d6): δ 14.73, 66.21, 111.71, 114.88, 115.18, 124.89, 125.24, 126.99, 127.04, 130.59, 132.22, 134.34, 137.50, 142.17, 152.17, 164.25; MS m/z: (330)+; Anal. Calcd for C18H14N6O (330.35): C 65.45, H 4.27, N 25.44. Found: C 65.98, H 3.98, N 25.37.
2-Methoxy-3-phenyl-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazoline (11e): This compound obtained as white solid with 0.237 g (75%). mp 196-198 oC; 1H-NMR (400 MHz, DMSO-d6): δ 4.02 (s, 3H), 7.62-8.76 (m, 9H), 13C-NMR (100 MHz, DMSO-d6): δ 57.46, 111.94, 115.17, 124.56, 126.12, 127.09, 128.35, 129.80, 130.59, 130.89, 131.09, 141.82, 147.67, 149.47, 167.34; MS m/z: (316)+; Anal. Calcd for C17H12N6O (316.32): C 64.55, H 3.82, N 26.57. Found: C 65.08, H 3.67, N 26.41.
2-Methoxy-3-pyridyl-bis[1,2,4]triazolo[1,5-a:4׳,3׳-c]quinazoline (11f): This compound obtained as white solid with 0.244 g (77%). mp 207-210 oC; 1H-NMR (400 MHZ, DMSO-d6): δ 4.12 (s, 3H), 7.75-8.89 (m, 8H), 13C-NMR (100 MHz, DMSO-d6): δ 57.39, 111.24, 115.23, 124.39, 124.75, 127.29, 129.80, 130.59, 133.35, 142.52, 145.67, 150.03, 161.24; MS m/z: (317)+; Anal. Calcd for C16H11N7O (317.31): C 60.56, H 3.49, N 30.90. Found: C 61.10, H 3.52, N 31.27.
General procedure for the synthesis of 2-Alkoxy(aralkoxy)-tetrazolo[4,3-c][1,2,4]triazolo[1,5-a]quinazolines (13a-d):
Method A: A mixture of 2a,b,e,f (1 mmol) and NaN3 (1.2 mmol) in absolute DMF (5 mL) was heated at 90 oC in a nitrogen atmosphere for 24 h. After cooling, the reaction mixture was poured into water and saturated with brine solution. The resulting solid was filtered off, dried and recrystallized from MeOH.
Method B: To a stirred solution of sodium nitrite (1.2 mmol) in water (5 mL) was added dropwise at -5 oC a mixture of 3a,b,e,f (0.8 mmol) in 10% hydrochloric acid (1.6 mL). After stirring for 30 min, the precipitate was collected by filtration, washed thoroughly with water, dried and recrystallized from MeOH.
2-Methoxy-tetrazolo[4,3-c][1,2,4]triazolo[1,5-a]quinazoline (13a): This compound obtained as white solid with 0.130 g (54%). mp 174-178 oC; 1H-NMR (400 MHz, DMSO-d6): δ 3.99 (s, 3H), 7.18-7.95 (m, 4H); 13C-NMR (100 MHz, DMSO-d6): δ 56.36, 114.67, 116.23, 125.81, 128.27, 134.74, 136.49, 145.01, 157.32, 167.54; MS m/z: (241)+; Anal. Calcd for C10H7N7O (241.21): C 49.79, H 2.93, N 40.65. Found: C 50.12, H 3.18, N 40.42.
2-Ethoxy-tetrazolo[4,3-c][1,2,4]triazolo[1,5-a]quinazoline (13b): This compound obtained as white solid with 0.135 g (53%). mp 157-160 oC; 1H-NMR (400 MHz, DMSO-d6): δ 1.38 (t, 3H, J = 7.54 Hz), 4.46 (q, 2H, J = 13.98 Hz), 7.51-8.53 (m, 4H); 13C-NMR (100 MHz, DMSO-d6): δ 14.81, 66.81, 109.97, 115.52, 126.11, 127.51, 132.65, 134.99, 148.61, 167.43; MS m/z: (255)+; Anal. Calcd for C11H9N7O (255.24): C 51.76, H 3.55, N 38.41. Found: C 52.10, H 3.51 , N 38.56.
2-Benzyloxy-tetrazolo[4,3-c][1,2,4]triazolo[1,5-a]quinazoline (13c): This compound obtained as white solid; 0.161 g (51%), mp 178-180 oC; 1H-NMR (400 MHz, DMSO-d6): δ 5.75 (s, 2H), 7.37-8.35 (m, 9H); 13C-NMR (100 MHz, DMSO-d6): δ 71.57, 109.58, 115.08, 125.5, 127.72, 128.23, 128.75, 130.36, 134.21, 134.53, 135.47, 148.17, 160.43, 167.16; MS m/z: (317)+; Anal. Calcd for C16H11N7O (317.31): C 60.56, H 3.49, N 30.90. Found: C 60.96, H 3.64 , N 30.98.
2-Phenethyloxy-tetrazolo[4,3-c][1,2,4]triazolo[1,5-a]quinazoline (13d): This compound obtained as white solid with 0.198 g (60%). mp 169-173 oC; 1H-NMR (400 MHz, DMSO-d6): δ 3.22 (t, 2H, J = 7.50 Hz), 4.79 (t, 2H, J = 7.51 Hz), 7.23-8.67 (m, 9H); 13C-NMR (100 MHz, DMSO-d6): δ 34.83, 71.21, 115.57, 124.39, 126.10, 126.87, 127.56, 128.80, 129.35, 130.23, 134.99, 138.27, 142.32, 156.34, 167.54; MS m/z: (331)+; Anal. Calcd for C17H13N7O (331.34): C 61.63, H 3.95, N 29.59. Found: C 61.88, H 3.73, N 29.68.
General procedure for the synthesis 2-Alkoxy(aralkoxy)-(3H-thieno[3,2-d]pyrimidin-4-one[4,3-c][1,2,4]triazolo[1,5-a]quinazolines (15a,b): A mixture of 2d,e (1 mmol) and 3-aminothiophene-2-methylcarboxylic acid ester (2.2 mmol) in absolute dioxane (10 mL) was refluxed in the presence of NaH (0.4 mmol) for 21 h. The solvent was removed under reduced pressure and the residue was treated with water and MeOH. The resulting solid was filtered off and dried.
2-Pentyloxy-(3H-thieno[3,2-d]pyrimidin-4-one[4,3-c][1,2,4]triazolo[1,5-a]quinazoline (15a): This compound obtained as yellow solid with 0.307 g (81%). mp 236-240 oC; IR (KBr) ν max cm-1: 1670; 1H-NMR (400 MHz, DMSO-d6): δ 0.68 (t, 3H, J = 7.40 Hz), 1.14-1.18 (m, 4H), 1.50-1.65 (m, 2H), 4.02 (t, 2H, J = 7.60 Hz), 6.18-8.05 (m, 6H); 13C-NMR (100 MHz, DMSO-d6): δ 14.63, 22.18, 27.69, 28.63, 69.35, 114.82, 124.71, 124.25, 124.80, 134.50, 134.19, 147.72, 153.60, 167.84; MS m/z: (379)+; HRMS [M-H]- Calcd for C19H17N5O2S (379.44), found: 379.40.
2-Benzyloxy-(3H-thieno[3,2-d]pyrimidin-4-one[4,3-c][1,2,4]triazolo[1,5-a]quinazoline (15b): This compound obtained as yellow solid with 0.274 g (69%). mp 203-207 oC; IR (KBr) ν max cm-1: 1667; 1H-NMR (400 MHz, DMSO-d6): δ 5.32 (s, 2H), 6.48-8.05 (m, 11H); 13C-NMR (100 MHz, DMSO-d6): δ 73.57, 109.08, 116.08, 124.25, 127.02, 128.13, 128.75, 131.36, 131.93, 133.23, 134.21, 134.53, 135.47, 148.17, 160.43, 167.16; MS m/z: (399)+; HRMS [M-H]- Calcd for C21H13N5O2S (399.43), found: 399.47.

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