Application of methyl 6-bromo-5-fluoropyridine-3-carboxylate_Industrial additives

Application background and overview of methyl 6-bromo-5-fluoropyridine-3-carboxylate

Methyl 6-bromo-5-fluoropyridine-3-carboxylate can be used as a pharmaceutical synthesis intermediate. If 6-bromo-5-fluoropyridine-3-carboxylic acid methyl ester is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing and rinse the skin thoroughly with soap and water. If discomfort occurs , seek medical attention; if eye contact occurs, separate eyelids, rinse with boric acid-10B solution or normal saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Application structure of methyl 6-bromo-5-fluoropyridine-3-carboxylate

Applications of methyl 6-bromo-5-fluoropyridine-3-carboxylate

Methyl 6-bromo-5-fluoropyridine-3-carboxylate can be used as a drug synthesis intermediate, such as the preparation of 6-((3aR,5s,6aS)-5-((5-cyclopropyl-3- (2,6-Dichlorophenyl)isoxazol-4-yl)methoxy)hexahydrocyclopenta[c]pyrrole-2(1H)-yl)-5-fluoronicotinic acid methyl ester, The compound has excellent pharmacodynamic or pharmacokinetic properties in vivo or in vitro, showing good FXR activating activity and activation effect as well as excellent plasma drug exposure and bioavailability, and thus has good drug activity and in vivo metabolism. Advantage.

1) 5-Cyclopropyl-3-(2,6-dichlorophenyl)-4-(((3aR,5s,6aS)-octahydrocyclopenta[c]pyrrole- 5-yl)oxy)methyl)isoxazole (79 mg, 0.20 mmol) was dissolved in DMA (4 mL), and 6-chloro-5-fluoronicotinic acid methyl ester (38 mg, 0.20 mmol) and DIPEA (258 mg, 2.0 mmol) and stir overnight at 100°C-120°C. After cooling, water and ethyl acetate were added to the mixture, and the EA layer was washed with water, dried, and concentrated. The residue was purified by preparing a silica gel plate to obtain the title compound of this step (57 mg, yield: 50%). MSm/z(ESI):546[M+H]HNMR(MHz,DMSO-d6)δ:12.69(s,1H),8.42-8.41(m,1H),7.68-7.55(m ,4H),4.19(s,2H fluoroboric acid),3.90-3.89(m,4H),3.71-3.67(m,2H),3.41-3.32(m,2H),2.54-2.51(m,2H),2.34 -2.30(m,1H),1.69-1.65(m,2H),1.53-1.47(m,2H),1.16-1.06(m,4H).

2): 6-((3aR,5s,6aS)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy ) Preparation of hexahydrocyclopenta[c]pyrrole-2(1H)-yl)-5-fluoronicotinic acid: Dissolve the compound obtained in the first step (57 mg, 0.1 mmol) in MeOH (5 mL), and add NaOH (20 mg, 0.5 mmol), stirred at room temperature for 4 hours. After cooling, water and ethyl acetate were added to the mixture, the EA layer was washed with water, dried, and concentrated, and the residue was purified by preparing a silica gel plate to obtain compound 12 (43 mg, yield: 80%). MSm/z(ESI):532[M+H]HNMR(MHz,DMSO-d6)δ:12.69(s,1H),8.42-8.41(m,1H),7.68-7.55(m ,4H),4.19(s,2H),3.90-3.89(m,1H),3.71-3.67(m,2H),3.41-3.32(m,2H),2.54-2.51(m,2H),2.34-2.30 (m,1H),1.69-1.65(m,2H),1.53-1.47(m,2H),1.16-1.06(m,4H).