2-Chloro-4-fluorobenzothiazole

Pale yellow solid

General procedure: GP3-1: A solution of 2-halo substituted aniline (1.0 eq), potassium ethyl xanthate (1.2 eq or 2.2 eq, typically 2.2 eq) in 10 volume of anhydrous DMF was heated at 100 In a 50mL dry eggplant-shaped bottle equipped with a spherical reflux condenser and magnet, Add 2-chloro-4-fluorobenzo [d] thiazole (1 g, 5.3 mmol), 4-methoxybenzo [d] thiazol-2-amine (0.96 g, 5.3 mmol), Cuprous iodide (0.31g, 0.3mmol), potassium carbonate (1.47g, 10.6mmol), Dimethyl sulfoxide (20 ml) was heated to 100 C and reacted for 6 hours. After the reaction is over, Cool to room temperature, add water (60 ml), ethyl acetate (30 mL), extract 3 times, wash with water, It was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure.A black solid was obtained. The crude product was made of silica powder and purified by silica gel column chromatography [eluent: VPE: VEA = 5: 1] to obtain a black solid. After being slurried several times with ethyl acetate or methanol, a white solid compound (0.7 g, yield: 39%).General procedure: GP4-1: A mixture of substituted2-chlorobenzothiazole (1.0eq), N-Bocpiperazine (1.05 eq) and Na2CO3 (1.2 eq) inDMF (10 volume) was heated up at 100 0C for hours, the process ofwhich was monitored by TLC. The mixture was diluted by EA and added by water.After extraction by EA (2 times), the collected organic layers were washed by10% citric acid, and then brine, dried over Na2SO4 andconcentrated to give crude product, which could be used directly withoutfurther purification.GP4-2: N-Bocprotected amine in DCM (5 volume) was added by TFA (2.5 volume). The mixturewas stirred at rt for four hours and monitored by TLC. After consumption ofstarting material, volatile solvent was removed under reduced pressure and theresidue was neutralized by saturated Na2CO3 solution toobtain the slurry, which was extracted by 10% methanol in DCM (3 times). Theorganic layers were collected, dried and concentrated to give the desired freeamine, for direct use for next step.GP4-3: Free amine (1.0 eq) suspendedin DCM (10 volume) was added by aldehyde (1.1 eq) under N2atmosphere. The mixture was stirred at rt 15 min. Then trimethylsilylazide (TMSN3, 1.1 eq) was added, and stirring was kept foranother 15 min, followed by addition of isonitrile (1.0 eq). The mixture wasstirred at for 12 h. After removal of solvent, the residue was purified bypreparative TLC (DCM/MeOH as eluent) to give the product, which could bere-purified by trituration with ether.General procedure: GP3-1: A solution of 2-halo substituted aniline (1.0 eq), potassium ethyl xanthate (1.2 eq or 2.2 eq, typically 2.2 eq) in 10 volume of anhydrous DMF was heated at 100 0Cor 120 0C for 4 hours under nitrogen. TLC monitored the progress ofreaction. After completion, the reaction mixture was cooled to room temperature, diluted with water (10 volume) and neutralized by 1 M HCl solution to pH 5. Theformed precipitate was collected by filtration, rinsed with water, firstlydried by rotavapor, and then dried by oil pump to afford 2-mercaptobenzothiazole.GP3-2: 2-mercaptobenzothiazole in 10 volume ofanhydrous DCM, was added by sulfuryl chloride (SO2Cl2, 1volume) under ice-cooled condition. The mixture was stirred at rt for 1 hour, which was monitored by TLC. After consumption of starting material, the mixturewas diluted by 30 volume of ether, following quenching carefully by addingwater. Stirring was kept for 1 hour to make sure the SO2Cl2was totally consumed and product was released. Organic layer was collected, neutralized by saturated NaHCO3, dried over Na2SO4and purified by silica gel chromatograph to give the pure product, which wasfinally characterized by LC-MS and NMR.To a mixture of (lS, 3S)-3-((3-(tetrahydro-2H-pyran-4-yl)pyrazin-2- yl)oxy)cyclobutanamine hydrochloride (see PREPARATION 5D, 200 mg, 0.8 mmol) in NMP (4 mL) was added

Molecular Weight:187.62
XLogP3:3.4
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