0.5M 2-thiazole-zincbromide solution in THF (10 equiv.) was added to (S)-2-(4-(3 -(tert-butoxycarbonylamino)piperidin- 1 -yl)quino lin-6-yl)pyrimidin-4-yl tri- fluoromethanesulfonate (1.0 equiv.) (0.045 M) and Pd(dppf)Cl2-DCM (0.2 equiv.) in a microwave vial and the mixture submitted to 100° C for 10 min in microwave, filtered through 1 μm PTFE HPLC filter, eluting with EtOAc and concentrated.
Patent reference: WO2010026121 (Novartis)
Benzylzinc bromide (3.26 mL, 0.5M, 1.2 equiv) was added to a solution of bis(tri-tert-butylphosphine) palladium (104 mg, 0.15 equiv) and bromo pyridine (500 mg, 1.36 mmol) from the previous step in dioxane (9 mL) at rt. This solution was then stirred at room temperature until deemed complete by LC/MS (~ 2 h). Upon quenching with sat. NH4Cl, the mixture was extracted with EtOAc, washed with water and brine, dried over MgSO4 concentrated in vacuo, and chromato graphed (SiO2,10% to 33% EtOAc/hexanes) to provide coupled product (260 mg, 51%).
Patent reference: WO2010026075 (Roche)