2-Chlorothiazolo[4,5-b]pyridine

To a slurry of thiazolo[4, 5-bjpyridine-2-thiol (343 mg, 2.039 mmol) indichloromethane (0.5 mL) was added sulfuryl chloride (3.32 mL, 40.8 mmol). The suspension was stirred at 50 °C for 2.0 h, and at room temperature overnight. To the yellow suspension was added ice water, stirred at room temperature for 15 mm todecompose the excess sulfuryl chloride. EtOAc and 4.0 N NaOH were added to adjustthe pH to 10-12. The organic layer was collected, washed with brine, dried over sodium sulfate. After evaporation of solvent, the cmde product was dissolved in a small amount of chloroform and charged to a 12 g silica gel cartridge which was eluted with 5percent for 3 mm., then a 12 mm gradient from 5percent to 60percent. The desired fractions were combined andconcentrated to give Intermediate 9A (265 mg, 1.553 mmol, 76 percent yield) as a white solid.‘H NMR (500MHz, chloroform-d) 8.76 (dd, J5.0, 1.7 Hz, 1H), 8.19 (dd, J8.0, 1.7Hz, 1H), 7.39 (dd, J=8.0, 4.7 Hz, 1H); LC-MS: method A, RT = 1.22 mm, MS (ESI) m/z:171 and 173 (M+H)The intermediate [1 , 3]thiazolo[4, 5-b]pyridine-2(3H)-thione (644.0 mg, 3.83 mmol, dry powder) was treated with neat sulfuryl chloride (3.08 ml, 38.28 mmol) and allowed to stir at it overnight. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with IN NaOH, followed by brine, and dried over NaExample 8 7-(Thiazolo[4, 5-b]pyridin-2-yl)-1, 3, 7-triazaspiro[4.4]nonane-2, 4-dione The title compound was obtained in analogy to example 3 using General procedure: Method A:41 To a round bottom flask was added tryptoline (21mg, 0.100mmol), 2-chlorobenzothiazole (31mg, 0.150mmol), K2CO3 (70mg, 0.500mmol) and DMF (2.0mL), and the reaction mixture was stirred for 12h at 110C. After the reaction was then cooled to room temperature, ethyl acetate (10mL) and H2O (10mL) were added into the mixture, and the aqueous layer was extracted with 2×10mL ethyl acetate. The organic layer then was combined and washed with brine, and dried over Na2SO4. The solvents were removed under vacuum, and the residue was purified by flash chromatography on silica gel using ethyl acetate/hexane as eluent.To Intermediate 1-1 (17 mg, 0.05 1 mmol), Intermediate 9A (11.22 mg, 0.066mmol) and [1, 1?-bis(diphenylphosphino)ferrocenejdichloropalladium (II) complex with dichloromethane (1:1) (3.30 mg, 4.05 imol) was added toluene (0.9 mL) and EtOH (0.3 mL). The mixture was sonicated for 1 mm, and flushed with argon. To this was addedsodium carbonate (2M, 0.056 mL, 0.111 mmol). The reaction mixture was heated in amicrowave reactor at 130 C for 30 mm. HPLC and LCMS indicated a completion of the reaction. To the reaction mixture was added EtOAc/water. The mixture was stirred at room temperature for 15 mm. The organic layer was collected. After evaporation ofsolvent, the crude material was purified via preparative LC/MS (method D, 40-90% Bover 10 minutes) to yield the (11.2 mg). 'H NMR (500MHz, methanol-d4)8.93 (d, J=1.7 Hz, 1H), 8.73 (s, 1H), 8.72 (dd, J=4.7, 1.4 Hz, 1H), 8.47 (dd, J8.0, 1.4Hz, 1H), 7.89 (s, 1H), 7.71 (t, Ji-w = 71.53 Hz, 1H), 7.61 (s, 1H), 7.44 (dd, J8.0, 4.7 Hz, 1H), 2.71 (s, 3H); LC-MS: Method H, 0 to 100% B. RT = 2.59 mm, MS (ESI) m/z: 345.0 (M+H) Analytical HPLC purity (method B): 95%.

Molecular Weight:170.62
XLogP3:2.6
Hydrogen Bond Acceptor Count:3
Exact Mass:169.9705470
Monoisotopic Mass:169.9705470
Topological Polar Surface Area:54
Heavy Atom Count:10
Complexity:133
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes