Diisopropylethylamine → HCID 57919167, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2-(6-oxo-4-phenoxy-6H-pyridazin-1-yl)-propionic acid (Intermediate 19, 100.6 mg, 0.30 mmol) in methylene chloride (1.70 mL, 0.18M) at 25° C. was treated with N,N-diisopropylethylamine (160 μL, 0.91 mmol) followed by N,N,N′,N′-tetramethyl-O—(N-succinimidyl)uronium tetrafluoroborate (110.6 mg, 0.36 mmol). The resulting solution was stirred at 25° C. for 2.5 h. After this time, the reaction was treated with 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (Intermediate 1, 61.8 mg, 0.39 mmol). The resulting solution was stirred at 25° C. for 2 d. After this time, the reaction was partitioned between water (75 mL) and methylene chloride (3×75 mL). The combined organics were washed with water (3×100 mL), dried over sodium sulfate and concentrated in vacuo. Silica gel column chromatography (ISCO 40 g, 1/1-3/1 ethyl acetate/hexanes) afforded 3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(6-oxo-4-phenoxy-6H-pyridazin-1-yl)-propionamide (23.6 mg, 16.5%) as a white solid; ES+-HRMS m/e calcd for C25H31N5O4 [M+H+] 466.2449, found 466.2450. 1H-NMR (300 MHz, DMSO-d6) δ ppm 1.05 (s, 3H), 1.06 (s, 3H), 1.00-1.76 (m, 9H), 1.91 (m, 1H), 2.28 (m, 1H), 3.89 (s, 2H), 4.67 (s, 1H), 5.46 (dd, J=3.9, J=11.2 Hz, 1H), 5.72 (d, J=2.7 Hz, 1H), 6.39 (d, J=2.1 Hz, 1H), 7.29 (d, J=7.5 Hz, 2H), 7.36 (t, J=7.5 Hz, 1H), 7.46-7.64 (m, 3H), 8.12 (d, J=2.7 Hz, 1H), 10.79 (s, 1H).

Provenance & Evidence