Dichloromethane → N-[2-(3,4-Dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidinyl)acetyl]-N-[2-[[(1,1-dimethylethoxy)carbonyl]amino]ethyl]glycine 2,3,4,5,6-pentafluorophenyl ester

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Reaction Conditions

Reaction Steps

N-(N-Boc-2-aminoethyl)-N-[(1-thyminyl)acetyl]glycine (5) (2.00 g; 5.20 mmol) was dissolved in DMF (5 ml) and methylene chloride (15 ml) was added. Pentafluorophenol (1.05 g; 5.72 mmol) was added and the solution was cooled to 0° C. in an ice bath. DDC then was added (1.29 g; 6.24 mmol) and the ice bath was removed after 2 min. After 3 h with stirring at ambient temperature, the precipitated DCU was removed by filtration and washed with methylene chloride. The combined filtrate was washed twice with aqueous sodium hydrogen carbonate and once with saturated sodium chloride, dried over magnesium sulfate, and evaporated to dryness, in vacuo. The solid residue was dissolved in dioxane (150 ml) and poured into water (200 ml) at 0° C. The title compound was isolated by filtration, washed with water, and dried over an appropriate drying agent, in vacuo. Yield: 2.20 g (77%). An analytical sample was obtained by recrystallisation from 2-propanol. M.p. 174–175.5° C. Analysis for C22H23N4O7F5, found(calc.): C, 48.22(48.01); H: 4.64(4.21); N: 9.67(10.18). 1H-NMR (250 MHz, CDCl3):Due to the limited rotation around the secondary amide bond several of the signals were doubled in the ratio 6:1 (indicated in the list by mj. for major and mi. for minor). 7.01 ppm (s, mi., ArH); 6.99 ppm (s, mj., ArH); 5.27 ppm (unres. t, BocNH); 4.67 ppm (s, mj., T-CH2—CO—); 4.60 ppm (s, mi., T-CH2—CO—); 4.45 ppm (s, mj., CONRCH2CO2Pfp); 4.42 ppm (s, mi., CONRCH2CO2Pfp); 3.64 ppm (t,2H,BocNHCH2CH2-); 3.87 ppm (“q”,2H,BocNHCH2CH2—); 1.44(s,9H,t-Bu). FAB-MS: 551 (10; M+1); 495 (10; M+1-tBu); 451 (80; -Boc).

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