Imidazole → HCID 59200399, compound

Participants

Reaction Conditions

Reaction Steps

A stirred suspension of methyl 2-(thiazol-2-ylamino)isonicotinate (14.17 g, 60.23 mmol) in tetrahydrofuran (385 mL) was treated with lithium aluminum hydride (2.51 g, 66.25 mmol) at 23° C. The reaction was stirred at 23° C. for 1 hour then sodium hydroxide (5N, 20 mL) was added to the mixture which was stirred again for 2 more hours. The solid was filtered and washed with tetrahydrofuran and water. The combined washings and filtrate were concentrated to give the crude alcohol (11.17 g). The crude alcohol was dissolved in N,N-dimethylformamide (150 mL) and the resulting solution was treated with imidazole (6.60 g, 97.01 mmol) and tert-butyldimethylsilyl chloride (12.19 g, 80.84 mmol) at 23° C. The reaction was stirred for 1 hour, tert-butyldimethylsilyl chloride (6.0 g) was added again and the reaction stirred for 30 more minutes. N,N-Dimethylformamide was added and the residue was taken into dichloromethane/water/saturated ammonium chloride. The organic phase was separated and the aqueous phase was extracted with dichloromethane (3×). The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (Biotage, 0% to 70% ethyl acetate in hexanes) to give the title material (10.55 g, 61% two steps). 1H NMR (400 MHz, CDCl3) δ (ppm): 0.15 (6H, s), 0.98 (9H, s), 4.76 (2H, s), 6.81 (1H, br d, J=5.05 Hz), 6.84 (1H, d, J=3.54 Hz), 6.95 (1H, s), 7.48 (1H, d, J=3.54 Hz), 8.30 (1H, br d, J=5.31 Hz), 9.79 (1H, s). LC/MS (M+H)+: 322. HPLC ret. time (Condition A): 1.800 min.

Provenance & Evidence