2-Chloro-6-fluorobenzothiazole

White solid

To a round bottomed flask was added 2-amino-6-fluorobenzothiazole (1.0017 g, 5.96 mmol, Sigma-Aldrich Chemical Company, Inc.), copper (II) chloride (1.201 g, 8.93 mmol, Sigma-Aldrich Chemical Company, Inc.), and tert-butyl nitrite (1.063 ml, 8.93 mmol, Acros Organics) in ACN and was heated to 65° C. for 2 hours. Intermediates 2: a) 2-Chloro-6-fluoro-benzothiazole (2a); 0.5 g (2.97 mmol) of 6-fluoro-benzothiazol-2-ylamine is placed in the presence of isoamyl nitrite (0.52 g, 4.46 mmol) and CuCIa) General procedure: A mixture of the 2-mercaptobenzo[d]thiazole (>1 g, 1 equiv) and sul-furyl chloride (10 equiv) was stirred at 20–25 °C for 15 min. Next, H 2 O(2 equiv) was added and the mixture was stirred at 20–25 °C for anadditional 3 h. A sample was taken, quenched with MeCN/H 2 O (2:1)and analyzed by HPLC. After completion of the reaction, the mixturewas diluted with MeCN (5 volumes) and slowly quenched with H 2 O(20 volumes). The product precipitated from the aqueous solution.The solid was collected and washed with H 2 O. Drying under vacuumafforded the pure product. In the case of the liquid product 2-chloro-benzo[d]thiazole (13), the reaction mixture was extracted withEtOAc. The organic layer was then dried and concentrated to affordthe product as an oil.General procedure: A mixture of the 2-mercaptobenzo[d]thiazole (>1 g, 1 equiv) and sul-furyl chloride (10 equiv) was stirred at 20-25 C for 15 min. Next, H 2 O(2 equiv) was added and the mixture was stirred at 20-25 C for anadditional 3 h. A sample was taken, quenched with MeCN/H 2 O (2:1)and analyzed by HPLC. After completion of the reaction, the mixturewas diluted with MeCN (5 volumes) and slowly quenched with H 2 O(20 volumes). The product precipitated from the aqueous solution.The solid was collected and washed with H 2 O. Drying under vacuumafforded the pure product. In the case of the liquid product 2-chloro-benzo[d]thiazole (13), the reaction mixture was extracted withEtOAc. The organic layer was then dried and concentrated to affordthe product as an oil.6-fluorobenzo[d]thiazole-2-thiol (14.0 g, 0.075 mol) was suspended in dry DCM(100 mL) under nitrogen and cooled to 0 0C. Sulfuryl chloride (18.5 mL) was then added dropwise and the reaction was allowed to warm to RT and stirred for Ih. The reaction mixture was then poured on to crushed ice and extracted with DCM (4 x 300 mL). The combined organic extract was given brine wash (2 x 150 mL), dried (Na2SO/i) and concentrated. The crude compound was purified by column chromatography (Silica 100-200 mesh; 3-7 % ethyl acetate in hexane) to provide 2-chloro-6-fluorobenzo[d]thiazole as a white solid.6-Fluoro-benzothiazole-2-thiol was treated with sulfuryl chloride by the procedure described in PCT/US04/14036 to give the desired product, which was used in the next step without further purification. EI-MS m/z 187 (M+); 1H NMR (DMSO-J6) delta 8.00 (m, 2H), 7.40 (m, IH).6-Fluoro-2(3H)-benzothiazolone Prepared analogous to Example 8 from Procedure: 50 mg, 0.33 mmol of benzo[c][1, 2]oxaborol-1, 5(3H)-diol was dissolved in 5 mL of N-methylpyrrolidine, then 75 mg, 0.40 mmol was added. 2-Chloro-6-fluorobenzothiazole and 162.9 mg, 0.5 mmol of cesium carbonate, the mixture was stirred at room temperature overnight, then treated with ammonium chloride, extracted with ethyl acetate, washed with brine, dried and concentrated. Purified by preparative high-performance liquid phase separation to give 5-(6-fluorobenzothiazol-2-oxy)benzo[c][1, 2]oxaborol-1(3H)-ol, white solid 15 mg, yield 15%.

Molecular Weight:187.62
XLogP3:3.6
Hydrogen Bond Acceptor Count:3
Exact Mass:186.9658761
Monoisotopic Mass:186.9658761
Topological Polar Surface Area:41.1
Heavy Atom Count:11
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes