With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.247037-82-7,Thiazole-2-carboximidamide hydrochloride,as a common compound, the synthetic route is as follows.
A 1500 L reactor equipped with mechanical stirrer, thermometer and nitrogen bubbler was charged with 3-fluoro-2-methyl-benzaldehyde (32.68 kg, 23.66 mol, compound 8-a), IPA (256.5kg) and ethyl 3-oxobutanoate (30.78 kg, 23.65 mol, compound 8-b) at 20 C-30 C. To thereaction mixture was added piperidine (2.03 kg) and acetic acid (1.58 kg) at 20 C-30 C. After 4hours, to the resulting solution was added thiazole-2-carboxamidine hydrochloride (36.51 kg, 90wt%, 20.1 imol, compound 8-c) followed by addition of triethylamine (23.90 kg, 23.66 mol)over 50 mins. The reaction mixture was stirred at 25 C-30 C for another 12 hours and thenstirred at 70 C-75 C for 8 hours. After the reaction was finished, the reaction mixture wascooled to 30 C and water (261 kg) was added over 50 mins. The suspension was stirred at 20 C30 C for another 10 hours. The solid was collected by filtration and washed with IPA/water (v/v=1:1, 33 L) and water (33 L). The wet cake was dried in a vacuum oven (50C /Ca. 0.1 MPa) with a nitrogen bleed for 16 hours to afford the product Example 8 (61 kg, purity: 99.5 %, yield:83.9 %) as a yellow solid. ?H NMR (400 MHz, DMSO-d6) 5 9.86 (s, 1 H), 7.96 (d, J=3.2Hz, 1H),7.88 (d, J=3.2 Hz, 1H), 7.15-7.20 (m, 1H), 6.99-7.04 (m, 1H), 5.83 (s, 1H), 3.94 (q, J=7.2 Hz,2H), 2.48 (s, 3H), 2.44 (d, J=1.6 Hz, 3H), 1.09 (t, J=7.2 Hz, 3H); MS mle = 360.0 [M+H] ., 247037-82-7
Big data shows that 247037-82-7 is playing an increasingly important role.
Reference£º
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; CHEN, Junli; (58 pag.)WO2017/140750; (2017); A1;,
Thiazole | C3H3NS – PubChem
Thiazole | chemical compound | Britannica