2-Amino-6-benzothiazolol

In a 100 ml two-necked flask equipped with stir bar, appropriately substituted aryl thiourea (2) (5g, 29.7mmol) was dissolved in chloroform (30 mL). Then bromine (5 g, 29.7 mmol) in chloroform (15 mL) was placed in a dropping funnel and was added drop wise with stirring to the reaction mixture by maintaining the temperature below 5°C. After the complete addition of bromine, the stirring was continued for a period of 4-6 h, and the content of the flask was refluxed on water bath till the evolution of hydrogen bromide vapors ceased. The resulting solid material was treated with ice water and filtered off. The filtrate was neutralized with an aqueous ammonia solution, the white precipitate obtained was filtered off, washed with water; compound 3 was crystallized from ethanol (4g, 80percent yield, solid white powder). To a solution of Example 18d (444 mg, 2.67 mmol) in Tol (10 mL) was added A1C11. A 22 L 3 -neck round bottom flask was equipped with a mechanical agitator, thermocouple probe, reflux condenser, and a heating mantle.2. The flask was charged with 48percent hydrobromic acid (14 L, 123.16 mol, 13.10 eq). The heating was initiated and 2-amino-6- methoxybenzothiazole was added (1.7 Kg, 9.4 mol, 1.00 eq) with stirring over 10 minutes.3. The heating of the reaction mixture was continued to reflux, and maintained (> 107 A. Preparation of 2-amino-6-hydroxybenzothiazole 1.; Example A-l; To a 1-L 3-necked round bottom flask fitted with a condenser, heating mantle, and mechanical stirrer was charged aqueous hydrobromic acid (48percent, 632 mL, 5.6 mol, 10 equiv). 2-Amino-6-methoxybenzothiazole (100 g, 0.55 mol, 1 equiv) was added to the above flask over 15 minutes. The reaction temperature was raised slowly to reflux (105-110 °C). A clear dark brown colored solution was observed at about 80 °C. The reflux was continued at 105-110 °C for about 4 hr. The progress of the reaction was monitored by HPLC. When 2-amino-6-methoxybenzothiazole was less than 2percent, the reaction was substantially complete.[00253] The reaction mass was cooled to 0-5 °C and at this point precipitation of a solid was observed. The mixture was maintained at 0-5 °C for 0.5 hr and filtered, and the cake was pressed to remove HBr. The wet cake was transferred to a 2-L round bottom flask fitted with a mechanical stirrer. Saturated aqueous sodium bicarbonate solution (-1500 mL) was added slowly at ambient temperature, whereupon considerable frothing was observed. The pH of the solution was found to be about 6.5 to 7. The mixture was stirred for 0.5 hr at ambient temperature and filtered. The filter cake was washed with water (500 mL), dried on the filter and then under vacuum at 30-35 °C for 10-12 hr to give the product 2-amino-6-hydroxybenzothiazole (82 g, 89percent yield, HPLC purity = 99percent). [1082] Step 1: 2-aminobenzo[d]thiazol-6-ol[1083] A mixture of 6-methoxy-2-aminobenzothiazole (5.0 g, 27.74 mmol) in a bromic acid solution (48 percent, 41 mL) was refluxed for 5 hours and then cooled to room temperature. The reaction mixture was diluted with water and then neutralized with sodium carbonate. The resulting solid was filtered, washed with water, and then dried under reduced pressure to give 5.81 g of the titled compound as a gray solid.Step 1: Hydrobromic acid (208.60 g, 1.3 mol) was added to a 250 ml round bottom flask equipped with a mechanicalstirrer over 15 minutes, and then 2-amino-5-methoxybenzothiazole (17 g, 94.32 mmol) was added thereto. The mixturewas heated and refluxed for 4 hours, then cooled to 0-5 °C until a solid precipited, then stirred for half an hour at 0-5 °Cand then the suction filtration under reduced pressure was performed. The solid was transferred to a 1 L round bottomflask and slowly added with saturated sodium carbonate solution under mechanical stirring to adjust till the pH was 6.5to 7, and then stirred at room temperature for 0.5 hour, filtered and the filter cake was washed with 300 ml of water, andthen dried under vacuum at 50 °C to give a gray compound 161A as solid (11.7 g, the yield was 74.64percent).1H NMR (400MHz, DMSO-d6) = 9.11 (s, 1H), 7.15 (s, 1H), 7.12 (s, 2H), 7.03 (d, J=2.3 Hz, 1H), 6.65 (dd, J=2.3, 8.5 Hz, 1H)A. The intermediate 2-amino-1, 3-benzothiazol-6-ol was prepared according to a slightly modified literature procedure by Lau and Gompf: J. Org. Chem. 1970, 35, 4103-4108. To a stirred solution of thiourea (7.6 g, 0.10 mol) in a mixture of 200 mL ethanol and 9 mL concentrated hydrochloric acid was added a solution of 1, 4-benzoquinone (21.6 g, 0.20 mol) in 400 mL of hot ethanol. The reaction was stirred for 24 hours at room temperature and then concentrated to dryness. The residue was triturated with hot acetonitrile and the resulting solid was filtered and dried. The free base was obtained by dissolving the hydrochloride salt in water, neutralizing with sodium acetate, and collecting the solid by filtration. The product (2-amino-1, 3-benzothiazol-6-ol) was obtained as a dark solid that was pure by LCMS (M+H=167) and NMR. Yield: 13.0 g (78percent). NMR (DMSO-d6) '7.6 (m, 2H), 6.6 (d, 1H).

Molecular Weight:166.20
XLogP3:1.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Exact Mass:166.02008399
Monoisotopic Mass:166.02008399
Topological Polar Surface Area:87.4
Heavy Atom Count:11
Complexity:155
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes