As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 848139-78-6, name is 6-Amino-4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-7-ethoxyquinoline-3-carbonitrile, molecular formula is C24H20ClN5O2, The compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below. Safety of 6-Amino-4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-7-ethoxyquinoline-3-carbonitrile
Example 2: Process 24-Dimethylaminocrotonoyl chloride hydrochloride and its coupling with 6-amino-4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-7-ethoxyquinoline-3-carbonitrile (procedure with phosphorus oxychloride and DMAc). A suspension of 4-dimethylaminocrotonic acid (6.70 kg, 40.4 mol) in DMAc (64.3 kg) was cooled to -14 to -19 0C. Neat POCI3 (6.15 kg, 40.1 mol) was added to the slurry at a rate to maintain the temperature in the reactor in the above range (moderate exotherm). The reaction mixture was held at -15 0C for 2-3 hrs. Conversion of the acid to acid chloride was monitored by HPLC: an aliquot of the reaction mixture was quenched into anhydrous ethanol and the solution was analyzed by HPLC using SIELC Primesep 200 column capable of retaining polar compounds. The conversion was calculated as a ratio of peak areas corresponding to the starting acid and its ethyl ester formed by reaction of the acid chloride with ethanol. After conversion reached the maximum (usually 85 to 95% after 2 to 3 hours), a solution of the aminoquinoline (12.6 kg, 28.3 mol) in DMAc (99.4 kg) was added to the reactor maintaining the temperature in the -14 to -19 0C range. Resulting mixture was held for 5 hr at approximately – 15 0C. At this point HPLC analysis showed residual aniline level at or below 0.5%. The thick suspension of the hydrochloride salt of the coupled product was quenched with water (87.1 kg) maintaining the batch temperature between -7 to -16 0C. The resulting clear solution in was warmed to 37-42 0C and its pH was adjusted to 10-1 1 with a 25% aqueous solution of KOH (approx. 53 kg of the solution was added). The suspension was further diluted with water (95 kg) and the solids were filtered on a polypropylene cloth filter. The cake was washed with water until neutral pH of the washes and dried first in the nitrogen flow on the filter and then on trays in vacuum at 45 to 50 0C to afford crude (E)-Lambda/-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)- 3-cyano-7-ethoxyquinolin6-yl)-4-(dimethylamino)but-2-enamide (15.75 kg, 94%) as a bright- yellow crystalline solid.
With the rapid development of chemical substances, we look forward to future research findings about 848139-78-6.
Reference:
Patent; WYETH LLC; GONTCHAROV, Alexander; ENG, Kan Kaung; SUTHERLAND, Karen; SEBASTIAN, Alice; YU, Qing; PLACE, David William; WO2010/48477; (2010); A2;,
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