[CH2:1]([O:3][C:4](=[O:14])[CH2:5][C:6]1[NH:7][C:8](=[O:13])[CH:9]=[C:10](Cl)[N:11]=1)[CH3:2].Cl.[NH:16]1[CH2:21][CH2:20][O:19][CH:18]([CH2:22][OH:23])[CH2:17]1.[Na+].[Cl-].C(Cl)Cl>CS(C)=O.C(N(CC)CC)C.C(OC(C)C)(C)C>[CH2:1]([O:3][C:4](=[O:14])[CH2:5][C:6]1[NH:7][C:8](=[O:13])[CH:9]=[C:10]([N:16]2[CH2:21][CH2:20][O:19][CH:18]([CH2:22][OH:23])[CH2:17]2)[N:11]=1)[CH3:2]
Under argon, in a 500 ml round-bottomed flask equipped with a thermometer and a condenser, 10 g of (4-chloro-6-oxo-1,6-dihydropyrimidin-2-yl)acetic acid ethyl ester (example 25b, step 5b) and 9.6 g of morpholin-2-yl-methanol hydrochloride obtained previously are successively placed in 200 ml of DMSO and 16.1 ml of triethylamine. The reaction medium is heated for 22 h at 85° C. After returning to ambient temperature (20° C.), the reaction medium is poured into a saturated NaCl solution, and the mixture is extracted with 8×250 ml of ethyl acetate. The organic extracts are combined, dried over magnesium sulfate, filtered, and evaporated under reduced pressure. A solid is obtained which is slurried in diisopropyl ether containing 10% of methylene chloride. The solid is filtered off, and rinsed twice and then once with pentane. [4-(2-Hydroxymethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid ethyl ester is isolated (1.9 g; yield=14%) in the form of a beige solid.
불러오는 중…
