Methyl 6-chloro-2,4-diMethylnicotinate synthesis

Yield:630082-81-4 71%

Reaction Conditions:

with lithium hydroxyde monohydrate in tetrahydrofuran;methanol;lithium hydroxide monohydrate at 20; for 2 h;

Steps:

358.A Example 358: 6-[[5-[5-[[(1R,5S,7s)-9-acetyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl]oxy]-2- methyl-4-pyridyl]pyrazolo[1,5-a]pyridin-2-yl]amino]-N,2,4-trimethyl-pyridine-3-carboxamide.

Step A. 6-chloro-2,4-dimethylnicotinic acid. To a solution consisting of methyl 6-chloro- 2,4-dimethylnicotinate (500 mg, 2.51 mmol, 1 equiv.), H₂O (2 mL), MeOH (4 mL) and THF (4 mL) was added lithium hydroxide monohydrate (210 mg, 5.01 mmol, 2 equiv). The mixture was stirred at room-temperature for 1 hr. To the mixture was added additional lithium hydroxide methylnicotinic acid. To a solution consisting of methyl 6-chloro- 2,4-dimethylnicotinate (500 mg, 2.51 mmol, 1 equiv.), H₂O (2 mL), MeOH (4 mL) and THF (4 mL) was added lithium hydroxide monohydrate (210 mg, 5.01 mmol, 2 equiv). The mixture was stirred at room-temperature for 1 hr. To the mixture was added additional lithium hydroxide

References:

WO2022/165529,2022,A1 Location in patent:Page/Page column 367; 368