Formaldehyde → HCID 66634726, compound

Participants

Reaction Conditions

Reaction Steps

A 37% aqueous solution of formaldehyde (400 μL, 4.8 mmol, 6.0 equiv) was added to a stirred solution of sodium methanethiolate (170 mg, 2.4 mmol, 3.0 equiv) in water (2.0 mL) at 23° C. The resulting colorless solution was stirred at 23° C. for 2 h. The reaction mixture was extracted with diethyl ether (3×2 mL). The combined organic layers were dried (magnesium sulfate) and gravity-filtered. Pyridine (320 μL, 3.9 mmol, 5.0 equiv) was added and the resulting solution was added to a stirred 20% solution of phosgene in toluene (4.0 mL, 7.8 mmol, 10 equiv) at 0° C. The resulting white mixture was allowed to warm to 23° C. and stirred for 2 h. The reaction mixture was gravity filtered and concentrated under vacuum. The residue was added to a stirred suspension of N-methyl-5-(pyridin-3-yl)-1,3,4-thiadiazol-2-amine (150 mg, 0.78 mmol, 1.0 equiv) and 4-dimethylaminopyridine (290 mg, 2.4 mmol, 3.0 equiv) in 1,2-dichloroethane (7.8 mL) at 23° C. The resulting yellow solution was heated to 75° C. for 18 h. The cooled reaction mixture was diluted with a saturated solution of sodium bicarbonate (50 mL) and extracted with ethyl acetate (3×40 mL). The combined organic layers were dried (MgSO4), gravity-filtered, and concentrated by rotary evaporation. The residue was purified by silica gel column chromatography (ethyl acetate) to afford the title compound as a yellow film (27 mg, 12%): IR (KBr thin film) 2919 (w), 1647 (s), 1570 (w) cm−1; 1H NMR (300 MHz, CDCl3) δ 8.89 (br s, 1H), 8.64 (br s, 1H), 7.97 (dt, J=8, 2 Hz, 1H), 7.37 (dd, J=8, 5 Hz, 1H), 5.12 (s, 2H), 3.14 (s, 3H), 2.32 (s, 3H).

Provenance & Evidence