2-Bromo-5-methylthiazole

To a stirred solution of A solution of [0233] To a solution of 2-bromo-5-methyl-l, 3-thiazole (300 mg, 1.68 mmol, 1.0 equiv) in a mixture of dioxane/water (50/10 mL) were added Pd(dppf)Cl2.CH2Cl2 (138 mg, 0.17 mmol, 0.1 equiv) and potassium carbonate (465 mg, 3.36 mmol, 2.00 equiv) under nitrogen atmosphere. The mixture was stirred at 80 C for 2 h, cooled to r.t, and added water (60 mL). The aqueous layer was extracted with ethyl acetate (30 mL) three times. The combined organic layers were dried over Na2S04, concentrated under reduced pressure, and purified by silica gel column with ethyl acetate/petroleum ether (1/10) to give 330 mg (96%) of 4-(5- methyl-l, 3-thiazol-2-yl)benzaldehyde as a yellow solid. LRMS (ES) m/z 204 (M+H).A suspension of To a solution of 28 (1 g, 9.08 mmol, 1 eq) and 28.1 (1.94 g, 10.90 mmol, 1.2 eq) in 1, 4-dioxane (10 mE) was added potassium carbonate (2.50 g, 18.16 mmol, 2.0 eq) and degassed with argon for 15 mm. Copper iodide (0.345 g, 1.81 mmol, 0.2 eq) and 1, 2-dimethylethylenediamine (0.320 g, 3.63 mmol, 0.4 eq) was added and reaction mixture again degassed with argon for 5 mm followed by heating at 1100 C. for 16 h. After completion of reaction, reaction mixture was cooled to room temperature, transferred into water and product was extracted with ethyl acetate. Organic layer was combined, washed with brine solution, dried over sodium sulphate and concentrated under reduced pressure to obtain crude material. This was further purified by column chromatography and compound was eluted in 1.2% methanol in dichloromethane to obtain pure 28.2 (0.400 g, 2 1.25%). MS(ES): mlz 208.25 [M+H].A mixture of 2-[[4-chloro-3-(4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)pyrrolo[2, 3-b]pyridin-1 -yl]methoxy]ethyl-trimethyl-silane (P15) (4 .00 g, 9.78 mmol), 2- bromo-5-methyl-thiazole (1.15 ml, 11.74 mmol) and tris(dibenzylideneacetone)dipalladium (0) (447.99 mg, 0.49 mmol) was equally separated between 6 flasks. Each flask was purged and evacuated with nitrogen before a degassed solution of 1, 4-Dioxane (3 ml) and water (1 ml) was added. The resulting solutions were heated to 80 00 overnight. Further 2-bromo-5- methyl-thiazole (0.479 ml, 4.89 mmol) was added and the reaction mixtures were stirred overnight. The mixtures were allowed to cool to room temperature before being combined and filtered through celite. The liquors were concentrated under reduced pressure and the resulting residue was dissolved in DCM. The organics were washed with water. The aqueous layer was further extracted with DCM (x 2). The organics were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The obtained residue was chromatographed (Si02, 0-60% EtOAc: isohexane) to afford 2-[[4-chloro-3-(5-methylthiazol- 2-yl)pyrrolo[2, 3-b]pyridin-1-yl]methoxy]ethyl-trimethyl-silane (P24) (1.8 g, 4.74 mmol, 48.4 % yield) as a yellow oil which solidified upon standing, LCMS ES 380, 382 [M+H], Rt = 1.70 mins (Generic Basic Method).