Triethylamine → 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(2-methyl-pyrimidin-4-yl)-propionamide

Temperature

0 °C

A solution of 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 75, 200 mg, 0.622 mmol) in methylene chloride (5 mL) was treated with N,N-dimethylformamide (2 drops) and then cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (0.081 mL, 0.933 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred for 1 h. The reaction mixture was then concentrated in vacuo. The resulting yellow gel was diluted with methylene chloride (2 mL) and then slowly added to a mixture of 4-amino-2-methylpyrimidine (102 mg, 0.933 mmol) and triethylamine (0.173 mL, 1.24 mmol) in N,N-dimethylformamide (3 mL). The resulting reaction mixture was stirred at 25° C. for 24 h. The crude reaction mixture was directly purified by Biotage chromatography (FLASH 40S, Silica, 19/1 methylene chloride/methanol) to afford 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(2-methyl-pyrimidin-4-yl)-propionamide (15 mg, 6%) as a white foam: mp 89-94° C. (foam to gel); EI-HRMS m/e calcd for C21H24N4O3S (M+) 412.1569, found 412.1568.

1. customThe resulting reaction mixture
2. temperatureto warm to 25° C. where it
3. concentrationThe reaction mixture was then concentrated in vacuo
4. additionThe resulting yellow gel was diluted with methylene chloride (2 mL)
5. customThe resulting reaction mixture
6. stirringwas stirred at 25° C. for 24 h
7. customThe crude reaction mixture
8. customwas directly purified by Biotage chromatography (FLASH 40S, Silica, 19/1 methylene chloride/methanol)

ORD record

ord-0305b15bc69948febcc1489163f93965

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06610846B1