Lithium Hydroxide → HCID 178511411, compound

Participants

Reaction Steps

(S)-methyl 18-(4-((2-amino-4-hydroxypteridin-6-yl)methylamino)benzamido)-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14-diazanonadecan-19-oate (225 mg, 0.33 mmol, crude) in 6 M aqueous hydrochloric acid (20 mL) was stirred at ambient temperature for 2 hours. After this time, the reaction was purified by semi-preparative HPLC (0-70% H2O/CH3CN with 0.05% TFA over 25 minutes) to give a mixture of the desired acid and the methyl ester (190 mg) as a yellow solid. To this mixture lithium hydroxide (30 mg, 1.25 mmol) was added along with a 1:1 THF/H2O mixture (6 mL). This mixture was stirred at ambient temperature for 2 hours. After this time, the THF was removed under reduced pressure, and the reaction was purified by semi-preparative HPLC (0-70% H2O/CH3CN with 0.05% TFA over 25 min) to afford (S)-2-(4-((2-amino-4-hydroxypteridin-6-yl)methylamino)benzamido)-5-(2-(2-(2-aminoethoxy)ethoxy)ethylamino)-5-oxopentanoic acid (185 mg, 100%) as a yellow solid that was obtained from lyophilization: 1H NMR (500 MHz, DMSO-d6) δ 12.47 (vbs, 1H), 11.44 (vbs, 1H), 8.64 (s, 1H), 8.17 (d, J=7.5 Hz, 1H), 7.87 (t, J=5.5 Hz, 1H), 7.72 (bs, 2H), 7.65 (d, J=9.0 Hz, 2H), 6.93 (bs, 2H), 6.64 (d, J=9.0 Hz, 2H), 4.48 (s, 2H), 4.30-4.26 (m, 1H), 3.57-3.49 (m, 6H), 3.37 (t, J=6.0 Hz, 2H), 3.22-3.13 (m, 2H), 2.99-2.94 (m, 2H), 2.19 (t, J=7.5 Hz, 2H), 2.08-2.01 (m, 1H), 1.93-1.85 (m, 1H), exchangeable proton not observed (1H); ESI MS m/z=570 [M−H]−.

Provenance & Evidence