Diisopropylethylamine → L-Valyl-L-citrulline

Participants

Reaction Steps

To a room temperature solution of Fmoc-Val-Cit (2.18 g, 4.4 mmol, U.S. Pat. No. 6,214,345 to Firestone et al.) in anhydrous DMF (10 mL) was added DEA (10 mL). The reaction mixture was stirred at ambient temperature for 20 minutes. The reaction mixture was concentrated in vacuo to thick oil, and then was added drop wise to a flask containing diethyl ether (˜500 mL) to precipitate the crude product. The white precipitate was collected by filtration and washed with ethyl acetate (2×250 mL). After drying material in vacuo, it was dissolved in DMSO (30 mL), and maleimidocaproic acid-N-hydroxysuccinimide ester (1.42 g, 1.05 eq, Molecular Biosciences, Inc., Boulder Colo.) was added, followed by the addition or DIEA (0.843 mL, 1.1 eq). The reaction mixture was stirred ˜6 h, the DMSO solution was concentrated in vacuo to a volume of ˜2 mL. Product was purified on a semi-preparative HPLC system (stationary phase: C12, mobile phase: 0.1% TFA/H2O/MeCN) to give 1.19 g (2.55 mmol, 58% yield). ES-MS m/z 468.23 [M+H]+. 1H NMR (d6-DMSO) □: 8.15 (d, J=7.2 Hz, 1H), 7.75 (d, J=9.2 Hz, 1 H), 7.00 (s, 1 H), 5.93 (br s, 1 H), 5.38 (br s, 1 H), 4.21 (dd, J1=6.8 Hz, J2=2.148, 1 H), 4.1 (m, 1 H), 2.94 (br s, 2 H), 2.22-2.05 (m, 2 H), 1.93 (q, J=6.8, 1 H), 1.68 (m, 1 H), 1.6-1.2 (m, 7 H), 1.17 (t, J=7.6, 2 H), 0.86-0.80 (dd, J1=6.8 Hz, J2=9.0, 6 H).

Provenance & Evidence