1,2-Dichloroethane → 6,6-Dimethyl-2-[6-(2-methyl-3h-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-4h-1,4-benzoxazin-4-yl]-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of Example 42 (0.09 g, 0.27 mmol) in EtOH (3 mL) was added DIPEA (0.09 mL, 0.55 mmol) and 2-chloro-3-nitropyridine (0.043 g, 0.27 mmol). The reaction mixture was heated to 80° C. for 3 days, then cooled to r.t., poured into water (10 mL), and extracted with DCM (2×10 mL). The combined organic fractions were dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in EtOH (5 mL) and 20% w/w palladium on carbon (0.020 g) was added. The reaction mixture was stirred under an atmosphere of H2 at r.t. for 3 days, then filtered and concentrated in vacuo. The residue was dissolved in DCM (3 mL). AcOH (0.02 mL), EDC (0.095 g, 0.5 mmol) and HOBT (0.01 g, 0.05 mmol) were added and the reaction mixture stirred at r.t. for 18 h. DCM (5 mL) and aqueous sat. NaHCO3 solution (5 mL) were added. The organic fraction was separated, then concentrated in vacuo and the residue dissolved in AcOH (2 mL). The reaction mixture was heated to 120° C. under microwave irradiation in a sealed tube for 10 minutes, and then concentrated in vacuo. The residue was dissolved in DCM (10 mL), then washed with aqueous sat. NaHCO3 solution (2×10 mL). The organic fraction was separated and concentrated in vacuo. Purification by preparative HPLC (Method 6) gave the title compound (0.024 g, 20%) as a brown solid. δH (CDCl3) 8.26 (1H, d, J 2.3 Hz), 8.23 (1H, dd, J 4.7 and 1.3 Hz), 8.04 (1H, dd, J 7.9 and 1.3 Hz), 7.25 (1H, dd, J 7.9 and 4.7 Hz), 7.20-7.15 (1H, m), 7.15-7.10 (1H, m), 5.31 (1H, s), 4.42-4.29 (2H, m), 4.09-3.96 (2H, m), 2.76 (2H, s), 2.56 (3H, s), 1.28 (6H, s). LCMS (ES+) 447.4 (M+H)+, RT 2.36 minutes (Method 1).

Provenance & Evidence