Diisopropylethylamine → HCID 44199424, compound

Participants

Reaction Steps

To a solution of 6-isobutyl-4-methyl-pyridine-2-carboxylic acid (100 mg, 0.435 mmol) and DIPEA (169 mg, 1.31 mmol) in DMF (5 mL), TBTU (210 mg, 0.653 mmol) is added at 0° C. The mixture is stirred for 15 min at 0° C. before N—((S)-3-[2-ethyl-4-(N-hydroxycarbamimidoyl)-6-methyl-phenoxy]-2-hydroxy-propyl)-2-hydroxy-acet-amide (170 mg, 0.522 mmol) is added. Stirring is continued at 0° C. for 1 h. The reaction is quenched by adding water. The mixture is diluted with sat. aq. NaHCO3-solution and extracted with EA and two times with DCM. The combined org. extracts are dried over MgSO4, filtered and concentrated to give the crude hydroxy-amidine ester intermediate. This material is dissolved in dioxane (5 mL) and the mixture is stirred at 80° C. for 24 h. The solvent is evaporated and the crude product is purified on prep. TLC plates with DCM containing 10% of 7 N NH3 in methanol followed by prep. HPLC to give the title compound (21 mg) as a pale yellow oil; LC-MS: tR=1.00 min, [M+H]+=483.26; 1H NMR (CDCl3): δ 0.99 (d, J=6.8 Hz, 6H), 1.29 (t, J=7.5 Hz, 3H), 2.21 (hept, J=6.8 Hz, 1H), 2.36 (s, 3H), 2.48 (s, 3H), 2.72 (q, J=7.5 Hz, 2H), 2.79 (d, J=7.3 Hz, 2H), 3.47-3.55 (m, 1H), 3.74-3.92 (m, 3H), 4.16-4.24 (m, 3H), 7.18 (s, 1H), 7.23 (t br, J=5.8 Hz, 1H), 7.88 (s, 1H), 7.90 (s, 1H), 7.99 (s, 1H).

Provenance & Evidence