2-CYANO-6-HYDROXYBENZOTHIAZOLE

Pyridine hydrochloride (2.32 g) was added to 2-cyano-6-methoxybenzothiazole 31 (51.4 mg, 0.271 mmol) and heated to 200°C in an argon atmosphere to dissolve the pyridine hydrochloride, and the reaction mixture was stirred for 30 minutes. Pyridinium chloride (19.5 g) was added to 6-methoxybenzo [d] thiazole-2-carbonitrile (766 mg, 4.03 mmol) under argon atmosphere at room temperature. The obtained mixture was heated to 200 ° C. under an argon atmosphere to melt the pyridinium chloride and then stirred at 200 ° C. for 1 hour.The reaction mixture was allowed to cool to room temperature, 2 M hydrochloric acid (250 mL) was added, and the mixture was further extracted with ethyl acetate (3 × 100 mL). The combined organic layer was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (silica gel 85 g; hexane-ethyl acetate (1: 1)) to give 6-hydroxybenzo [d] thiazole-2-carbonitrile2-Cyano-6-hydroxybenzothiazole; Compound 1 was synthesized using a method modified from the literature (Yao H S, Min-kyung; Rao, Jianghong (2007) A bioluminogenic Substrate for In Vivo Imaging of beta-Lactamase Activity. Angew Chem Int Ed 46:7031-7034). Pyridine hydrochloride (1.0 g, 8.65 mmol) and 2-cyano-6-methoxybenzothiazole, Compound 2, (0.5 g, 2.63 mmol) were added to a 5 mL microwave flask with a stirbar. Nitrogen gas (NPyridine hydrochloride (1.0 g, 8.65 mmol) and 2-cyano-6-methoxybenzothiazole, 2, (0.5 g, 2.63 mmol) were added to a 5 mL microwave flask with a stirbar. In 500 ml is provided with a thermometer, dropping funnel, stirrer, drying tube in the four-port flask, add 150 ml acetonitrile, 2-cyano-6-methoxybenzothiazole 20g (105.14mmol), potassium iodide 26.18g (157.71mmol) stirring dissolved, add 0.65g (10.51mmol) ethyl mercaptan at -5 °C lower dropwise chlorotrimethylsilane 17.13g (157.71mmol) acetonitrile solution, after dripping, raising the temperature to 30 °C reaction 6 hours, after the reaction, quenching reaction adds by drops full and sodium carbonate aqueous solution, adjusted to pH 9, by adding ethyl acetate 100 ml extraction 3 time, combined with the phase, then using 100 ml water backwash organic phase 3 time, combined with the phase, drying, removing dissolved product 1 (15.38g, 83percent).General procedure: The methoxycarbonitrile derivative (1 eq) was mixed with pyridinium chloride (5 eq) under argon and heated to 210°C for 30 minutes. The resulting mixture was partitioned between distilled water and dicloromethane, and the organic layers were concentrated under vacuum. The crude product was dissolved in 5 percent NaEXAMPLE 6 EXAMPLE 3 2-Cyano-6-hydroxybenzothiazole STR7 4 g. of the mixture of 2-chloro-6-hyroxybenzothiazole and 2-iodo-6-hydroxybenzothiazole obtained in are added to a suspension of 3 g. potassium cyanide and 100 mg. 18-crown-6 in 150 ml. dimethyl sulphoxide heated to 120° C. and stirred at a bath temperature of 120° C. After a reaction time of 3 hours, the reaction mixture is poured in 1 liter of ice water and the solution obtained is acidified with dilute hydrochloric acid. Subsequently, it is extracted twice with 500 ml. amounts of diethyl ether and the extracts are washed with water, dried over anhydrous sodium sulphate, mixed with charcoal, filtered and the filtrate evaporated in a vacuum. 2.5 g. Crude 2-cyano-6-hydroxybenzothiazole are obtained. The crude product is suspended in 100 ml. water and mixed with a 1N aqueous sodium hydroxide solution, the material thereby dissolving in a short time with a little insoluble material remaining behind.2-Cyano-6-Hydroxybenzothiazole (0.50 g, 2.84 mmol) and 2-aminobenzenethiol(0.43 g, 3.4 mmol, 1.2 eq.) were dissolved in the mixedsolvent of=acetonitrile and water (v:v=4:1). Under stirring, 0.30 g(2.8 mmol) K2CO3 was added into the solution, and the system werestirring another 30 min at room temperature. Reaction solution wasextracted with CH2Cl2 two times. Precipitate appeared when adjusting pH of aqueous layer to 1 with HCl. The faint yellow solid was obtainedvia filtrating and washed twice with water, 0.34 g, and yield: 42%.1HNMR (DMSO-d6, 400 MHz): delta 10.22 (s, 1H, OH), 8.22 (d, J=7.9 Hz, 1H, ArH), 8.16 (d, J=8.0 Hz, 1H, ArH), 8.00 (d, J=8.9 Hz, 1H, ArH), 7.62 (t, J=7.6 Hz, 1H, ArH), 7.56 (t, J=7.5 Hz, 1H, ArH), 7.51 (d, J=1.8 Hz, 1H, ArH), 7.07-7.13 (m, 1H, ArH); 13CNMR: delta 161.83, 157.68, 157.58, 153.44, 147.08, 137.58, 135.35, 127.60, 127.19, 124.99, 123.88, 123.21, 117.71, 107.41. HRMS (ESI, m/z): calcd forC14H8N2OS2 [M + H+]=285.0151; found: 285.0168.In a 5-mL round-bottom flask, compound 3 (10 g, 56.7 mmol), hydroxylamine hydrochloride (7.8 g, 113.5 mmol) and 3, 4, 5-trimethoxybenzoic acid 4 (12 g, 56.7 mmol) were mixed with 4-(dimethylamino)pyridinium acetate (51.6 g, 283.5 mmol). The reaction mixture was heated to 100°C for 6 h. The mixture was cooled down to room temperature, ethanol (1 mL) was added, and stirring continued for 30 min more. Water (5 mL) was added to the reaction mixture. The solid product was filtered off, washed twice with water (2×5 mL) and purified by column chromatography with hexanes/ethyl acetate (3 : 7) to afford pure compound 5. Yield 75percent, mp 271'273°C. 1H NMR spectrum, delta, ppm: 3.88 s (3H), 3.92 s(6H), 7.28 d (1H, J = 7.56 Hz), 7.40 s (1H), 7.46 s (2H), 7.82 d (1H, J = 7.56 Hz), 9.67 s (1H). MS (ESI): 386 [M]+.

Molecular Weight:176.20
XLogP3:2.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:176.00443393
Monoisotopic Mass:176.00443393
Topological Polar Surface Area:85.2
Heavy Atom Count:12
Complexity:224
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes