2-Amino-4,5-dimethyl-1,3-thiazole → HCID 67425328, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4,5-dimethylthiazol-2-amine (0.30 g, 2.3 mmol, Aldrich) and (bromomethyl)cyclopropane (0.63 g, 4.7 mmol, Aldrich) was heated at 85° C. for 16 h. The reaction mixture was cooled to room temperature and triturated with ether to obtain the crude intermediate, hydrobromide salt of (cyclopropylmethyl)-4,5-dimethylthiazol-2(3H)-imine. To a solution of the above intermediate in tetrahydrofuran (10 mL) were added Example 24B (0.71, 2.3 mmol), N-(3-dimethylaminopropyl)-N-ethylcarbodimide hydrochloride (0.54, 2.8 mmol, Aldrich), 1-hydroxybenzotriazole (0.43 g, 2.8 mmol, Aldrich) and triethylamine (1.0 mL, 7.0 mmol, Aldrich). The reaction mixture was stirred at 80° C. for 2 h, cooled and then quenched with saturated NaHCO3 (10 mL). The aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 5-100% of triethylamine/MeOH/EtOAc (0.1/1/10) in hexanes) to afford 160 mg of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.32-0.69 (m, 4H), 1.14-1.40 (m, 1H), 1.48-1.75 (m, 3H), 1.78-2.00 (m, 1H), 2.07-2.22 (m, 1H), 2.23 (s, 3H), 2.29 (s, 3H), 2.32 (s, 3H), 2.53-2.64 (m, 1H), 2.86-2.97 (m, 1H), 3.92-4.07 (m, 2H), 4.11 (d, J=7.1 Hz, 2H), 7.28 (d, J=8.7 Hz, 1H), 7.72 (dd, J=8.7, 2.4 Hz, 1H), 7.92 (d, J=2.4 Hz, 1H); MS (ESI+) m/z 468 (M+H)+.

Provenance & Evidence