Extended knowledge of 2,2-Dimehtyl-N-pyridin-3-yl-propionamide

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,70298-88-3, its application will become more common.

Electric Literature of 70298-88-3, 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 70298-88-3 as follows.

To a solution of 2.67 g (15.0 mmol, 1 eq.) of pivalamide IV and 6.8 mL (45.0 mmol, 3 eq.) of TMEDA in 120 mL of dry diethylether, cooled to -78C, were added 18.0 mL (45.0 mmol, 3 eq., 2.5 M in hexane) of BuLi. After 15 minutes, the solution was brought back to -24C and stirred 2 hours. Then, the mixture was cooled down to – 78C before addition of 4.0 mL (33.0 mmol, 2.2 eq) of p-anisaldehyde in 60 mL of THF. The reaction was brought back to 0C and stirred 2 hours before being stirred at room temperature over night. Then, 120 mL of water were added. The aqueous layer was extracted with 2 x 80 mL of dichloromethane. The organic phase was dried, filtered and concentrated. The crude mixture was purified over silicagel. The obtained white solid (estimation 9 mmol of XII) was dissolved in 90 mL of DCM. Then, 7.74 g (89.0 mmol, 10 eq.) of activated Mn02 were added and the reaction was refluxed 20 hours. The reaction was brought back to room temperature and 7.74 g (89.0 mmol, 10 eq.) of activated Mn02 were added again. After 20 hours to reflux, the mixture was filtered on celite and the solvent was evaporated. The crude mixture was dissolved in 180 mL of 3 M aqueous HCI were added and refluxed 16 hours. The reaction was cooled down to 0C and 50 mL of aqueous ammonia were added. The aqueous layer was extracted with 3 x 90 mL of DCM. The organic phase was dried, filtered and concentrated. Purification over silica gel afforded 1.65 g (7.2 mmol, 48%) of XIII as a yellow solid. The yield varied from 38% to 48%. Rf=0.15 (PE/EtOAc 1 :2). 1H NMR (300 MHz): delta = 8.26 (s, 1 H), 7.94 (d, J = 5.1 Hz, 1 H), 7.72 (m, 2 H), 7.22 (m, 1 H), 6.96 (d, J = 5.1 Hz, 2 H), 5.58 (s, 2 H), 3.88 (s, 3 H) ppm. 13C NMR (75 MHz): delta = 196.5, 163.4, 144.0, 141.1 , 137.1 , 132.2, 130.6, 124.7, 123.4, 1 13.8, 55.6 ppm.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,70298-88-3, its application will become more common.

Reference:
Patent; LYTIX BIOPHARMA AS; STENSEN, Wenche; SCHEVENELS, Florian; MARKO, Istvan, E.; SVENDSEN, John, Sigurd, Mj°en; WO2014/198848; (2014); A2;,
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