Phosphorus oxychloride → 5-(2-Fluoro-6-methoxyphenyl)-1,3,4-thiadiazol-2-amine

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

A stirred mixture of 2-fluoro-6-methoxybenzoic acid (2 g, 11.7 6 mmol) and hydrazinecarbothioamide (1.607 g, 17.63 mmol) was cooled under nitrogen atmosphere in an ice bath and POCl3 (3.29 mL, 35.3 mmol) was added drop-wise. On completion of the addition, the reaction mixture was stirred at 78° C. for 3 hours. The reaction mixture was cooled in an ice bath and quenched by addition of ice water (˜50 mL) to give a solid/gum-like mass. This solid was sonicated for 1.5 hours and the resulting suspension was diluted with a further 50 mL of water then slurried at room temperature for ˜16 hours. The solid was collected by vacuum filtration, rinsed with water, re-suspended in saturated NaHCO3(aq) (˜100 mL) and slurried for ˜30 minutes. The resulting solid was collected by vacuum filtration, then rinsed with water to afford the crude product as an off-white solid. The crude material was pre-absorbed onto silica gel and purified by flash chromatography using a 120 g silica cartridge with a 0-10% MeOH/DCM gradient as the eluent to afford the title compound as a pale yellow solid (1.265 g, 45% yield). LC-MS: Rt 0.77 min; MS m/z 226.1 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.48 (td, J=8.34, 6.57 Hz, 1H), 7.29 (s, 2H), 7.02 (d, J=8.08 Hz, 1H), 6.91-6.99 (m, 1H), 3.85 (s, 3H).

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