Sodium Carbonate → HCID 86680138, compound

Participants

Reaction Steps

In a microwave reaction vial, tert-butyl N-[2-bromo-4-[[5-[(4R,5R)-4-(tert-butoxycarbonylamino)-5-fluoro-azepan-1-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (161 mg, 0.25 mmol), (4-methyl-3-pyridyl)boronic acid (105 mg, 0.76) and PD(DPPF)CL2 (19 mg, 0.025 mmol) were dissolved in acetonitrile (3 mL). 1.0M KOAc (0.38 mL, 0.38 mmol) and 1.0M Na2CO3 (0.38 mL, 0.38 mmol) were added and the reaction was irradiated with microwave at 125° C. for 30 min. The mixture was cooled, filtered through Celite, concentrated and purified via flash chromatography, EA/heptane 0% to 100% to afford tert-butyl N-[4-[[5-[(4R,5R)-4-(tert-butoxycarbonylamino)-5-fluoro-azepan-1-yl]-1-methyl-pyrazol-4-yl]carbamoyl]-2-(4-methyl-3-pyridyl)thiazol-5-yl]carbamate (95 mg, 58%). This compound was stirred with 4N HCl in dioxane (3 mL, 12 mmol) and methanol (2 mL) at room temperature for 3 h. Solvent was removed under reduced pressure. The residue was basified with saturated NaHCO3 and extracted with EA 3×. The combined organic layers were dried over MgSO4 and the solvent removed under reduced pressure and the residue purified by preparative HPLC to afford 428 (38 mg, 58%). 1H NMR (400 MHz, DMSO) δ 8.83 (s, 1H), 8.79 (s, 1H), 8.43 (d, J=5.0 Hz, 1H), 7.49 (s, 2H), 7.47 (s, 1H), 7.37 (d, J=4.9 Hz, 1H), 4.42 (dt, J=8.4, 5.0 Hz, 1H), 3.64 (s, 3H), 3.26-3.02 (m, 5H), 2.63 (s, 3H), 2.18-2.02 (m, 1H), 2.02-1.88 (m, 1H), 1.87-1.75 (m, 1H), 1.66-1.53 (m, 1H). LCMS (ES+) m/z 445 (M+1)

Provenance & Evidence