Water → HCID 59506393, compound

Participants

Reaction Conditions

Reaction Steps

To an ice-cooled solution of diisopropylamine (28.16 mL, 198.96 mmol) in tetrahydrofuran (400 mL) was added n-BuLi (15% in hexane, 82.5 mL, 192.93 mmol) dropwise and the mixture was then stirred at the 0° C. for 45 min. The reaction mixture was cooled to -78° C. and 4-chloro-6-((4-ethoxy-4-oxobutyl)(4-methoxybenzyl)amino)-2-(methylthio)pyrimidine-5-carboxylate (29.0 g, 60.17 mmol) in tetrahydrofuran (300 mL) was added to the mixture dropwise over 45 min. and the reaction mixture was stirred at −78° C. for 15 min and ice cooled water (1 L) was added to the reaction mixture at same temperature. The reaction mixture was then warmed to room temperature and extracted with EtOAc (500 mL×2). The combined organic layer was washed with water (1 L), dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to afford ethyl 4-chloro-9-(4-methoxybenzyl)-2-(methylthio)-5-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepine-6-carboxylate (23.5 g); which was used in the next step without any purification. 1HNMR (400 MHz, CDCl3): δ 7.19 (d, J=8.4 Hz, 2H), 6.87 (d, J=8.4 Hz, 2H), 5.17 (d, J=14.8 Hz, 2H), 4.23-4.16 (d, J=14.8 Hz, 2H), 4.12-4.06 (m, 1H), 3.85-3.83 (m, 1H), 3.80 (s, 3H), 3.45-3.33 (m, 2H), 2.72-2.64 (m, 1H), 2.47 (s, 3H), 2.29-2.22 (m, 1H), 1.17 (t, J=7.2 Hz, 3H). LCMS [M+H]: 436

Provenance & Evidence