2-(N-Methylaminocarbonyl)-5-pyridineboronic acid pincol ester synthesis

Yield:-

Reaction Conditions:

with potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ in 1,4-dioxane at 110; for 1 h;Inert atmosphere;Microwave irradiation;Suzuki Coupling;

Steps:

6

Example 6; Preparation of 5-(2-Acetamidothiazolo[5,4-Z>]pyridin-5-yl)-N- methylpicolinamide (6); PcIdPPfCI₂-CH₂CI₂ KOAc, 1 ,4-dioxane microwave, 110 ⁰C Example 1 ditbpfPdCI₂, Cs₂CO₃ NaHCO₃(Sat.), DMF, microwave, 110-120 ⁰C[0381] A mixture of 5-bromo-N-methylpicolinamide (320 mg, 1.48 mmol), bispinacolatodiboron (752 mg, 2.96 mmol), PddppfCl₂-DCM (cat.), KOAc (436 mg, 4.44 mmol) in 1,4-dioxane (5 mL, degassed) was heated at 110 ⁰C in a microwave for 1 h. To this mixture was then added Example 1 (608 mg, 2.22 mmol), ditbpfPdC12 (cat.), Cs₂CO₃ (1.45 g, 4.44 mmol), NaHCO₃ (sat., 1 mL) and DMF (dry, degassed, 1 mL). It was heated in a microwave at 110⁰C for 1 h, then at 120 ⁰C for another hour. The reaction mixture was purified by HPLC to give the titled compound as a white solid. ¹H NMR (400 MHz, DMSO-rfβ) δ ppm 12.53 (s, IH), 9.28 (d, J=4 Hz, IH), 8.79 (m, IH), 8.61 (dd, J=8 Hz, IH), 8.18 (m, 2H), 8.08 (d, J=8 Hz, IH), 2.78 (d, J=4 Hz, IH), 2.18 (s, 3H); [M+H] calc'd for Ci₅Hi₃N₅O₂S, 328; found, 328.

References:

WO2010/8847,2010,A2 Location in patent:Page/Page column 125-126