Hydrochloric Acid → HCID 72202161, compound

Participants

Reaction Conditions

Reaction Steps

SOCl2 (1.218 mL, 16.68 mmol) and DMF (208.24 μL) were added dropwise to a suspension of 3-iodo-4-(methoxycarbonyl)benzoic acid (1.0212 g, 3.34 mmol) in toluene (8.37 mL) and the RM was stirred at 80° C. for 1 h. The solvent was evaporated off under reduced pressure and the residue was dissolved in THF (6.27 mL). DIPEA (1.166 mL, 6.67 mmol) was added and the mixture was cooled down to 0° C., treated dropwise with a solution of 4-(trifluoromethoxy)aniline (0.496 mL, 3.67 mmol) in THF was added and the RM was stirred at RT for 2.5 h. The RM was treated with 1 M HCl and extracted with EtOAc. The combined extracts were washed with HCl 1 M, NaHCO3 10%, brine, dried over MgSO4 and the solvent was evaporated off under reduced pressure to give a residue, of which (500 mg, 1.075 mmol), together with pyrimidin-5-ylboronic acid (266 mg, 2.150 mmol), Pd(PPh3)2Cl2 (75 mg, 0.107 mmol), Na2CO3 (342 mg, 3.22 mmol), water (1.30 mL), EtOH (656 μL) and DME (4.58 mL), were added to a vial, which was sealed, evacuated/purged with argon and subjected to MW irradiation for 10 min at 120° C. RM was diluted with DME (3 mL) and stirred overnight with Si-Thiol (1.3 mmol/g, 413 mg, 0.537 mmol). The mixture was centrifuged, filtered and the filtrate was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel, cyclohexane/EtOAc, 2% to 50% EtOAc) to afford the title compound as a yellow solid. UPLC-MS (Condition 2) tR=1.08 min, m/z=418.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.72 (s, 3H) 7.40 (d, J=8.21 Hz, 2H) 7.88 (m, J=9.00 Hz, 2H) 8.08 (s, 1H) 8.16 (s, 2H) 8.88 (s, 2H) 9.24 (s, 1H) 10.62 (s, 1H).

Provenance & Evidence