In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 3676-85-5 as follows. Recommanded Product: 5-Aminoisoindoline-1,3-dione
A mixture of l-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[l ,2-b]pyridazin-6-yl) piperidine-3- carboxylic acid (500 mg, 1.26 mmol), 5-aminoisoindoline-l ,3-dione (250 mg, 1.51 mmol) and pyridine (10 mL) was stirred at 0C for 2 h. POCI3 (20 drops) was added and stirred for 10 mins, then water (5 mL) was added and the mixture extracted with ethyl acetate (10 mL). The organic layer was washed with brine (10 mL), then dried over Na2S04, filtered and concentrated in vacuo The crude product was purified by prep-HPLC (Gemini 5u CI 8 150×21.2 mm; inject volume: 3mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; gradient conditions: 20 % acetonitrile/80 % water (0.1 % TFA, v/v) initially, proceeding to 50 % acetonitrile/50 % water (0.1 % TFA, v/v) in a linear fashion over 9 min) to give the product. HC1 (1 mL) was added and then the mixture concentrated in vacuo to give l-(8-(5,6-dimethoxypyridin-2- ylamino)imidazo[l ,2-b]pyridazin-6-yl)-N-(l ,3-dioxoisoindolin-5-yl)piperidine-3-carboxamide hydrochloride (10 mg, 2 %). 1H NMR (300 MHz, DMSO): delta 1 1.23 (s, 1H), 10.65 (s, 1H), 10.21 (s, 1H), 8.15 (s, 2H), 7.98 (s, 1H), 7.86 (d, 1H, J = 8.4 Hz), 7.77 (d, 1H, J= 7.8 Hz), 7.43 (d, 1H, J = 8.1 Hz), 6.93 (d, 1H, J = 8.1 Hz), 4.29 (d, 1H, J = 1 1.7 Hz), 4.14 (d, 1H, J = 12.3 Hz), 3.91 (s: 3H), 7.56 (s, 3H), 3.23 – 3.02 (m, 2H), 2.73 (s, 1H), 2.10 – 2.06 (s, 1H), 1.82 – 1.75 (m, 3H). LC- MS : [M+H]+, 543, tR = 1.406 min, HPLC: 98.08 % at 214nm, 98.69 % at 254nm, tR = 5.25 mm.
According to the analysis of related databases, 3676-85-5, the application of this compound in the production field has become more and more popular.
Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HERMANN, Johannes Cornelius; KUGLSTATTER, Andreas; LUCAS, Matthew C.; PADILLA, Fernando; WANNER, Jutta; ZHANG, Xiaohu; WO2013/64445; (2013); A1;,
Indoline – Wikipedia,
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