Reaction #1702038

Reaction equation

5-[2-(2-azidoethoxy)ethoxy]-4-oxopentanoic acid

EDC

camptothecin

→

Camptothecin azide

Solvents

dichloromethane

Conditions

Workup

1. 1
   ConcentrationThe reaction mixture was then concentrated
2. 2
   Washwas eluted first with 1-2% methanol in dichloromethane
3. 3
   ConcentrationThe appropriate fractions were then concentrated
4. 4
   Otherto give the desired conjugate as a yellow solid

Procedure

A solution of 70 mg of 5-[2-(2-azidoethoxy)ethoxy]-4-oxopentanoic acid in 10 mL of dichloromethane was cooled in an ice-water bath, and treated with 55 mg of EDC, followed by 35 mg of DMAP and 50 mg of camptothecin. The reaction was then allowed to warm to room temperature and stirred overnight as the solution slowly became homogeneous. The reaction mixture was then concentrated and applied to a silica gel column, which was eluted first with 1-2% methanol in dichloromethane. The appropriate fractions were then concentrated to give the desired conjugate as a yellow solid. 1H NMR (400 MHz, CDCl3): δ=0.98 (t, J=7.6H), 1.98 (quintet, J=7.2 Hz, 2H), 2.13-2.32 (complex m, 2H), 2.45 (t, J=7.6 Hz, 2H), 2.51-2.65 (complex m, 2H), 3.35 (t, J=5 Hz, 2H), 3.63-3.68 (m, 4H), 4.21-4.25 (m, 2H), 5.30 (br s, 2H), 5.41 (d, J=17.2 Hz, 1H), 5.68 (d, J=17.2 Hz, 1H), 7.21 (s, 1H), 7.68 (t, J=6.8 Hz, 1H), 7.84 (app t, J=8.4 Hz, 1H), 7.95 (d, J=8 Hz, 1H), 8.23 (d, J=8 Hz, 1H), 8.40 (s, 1H).

Source