1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57919113, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2-[4-(methyl-phenyl-amino)-6-oxo-6H-pyridazin-1-yl]-propionic acid (assume 0.18 mmol) in methylene chloride (1.8 mL, 0.1M) at 25° C. was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (34 μL, 0.19 mmol) followed by 1-hydroxybenzotriazole (26.3 mg, 0.19 mmol). The resulting solution was stirred at 25° C. for 3.5 h. After this time, the reaction was treated with 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (Intermediate 1, 36.8 mg, 0.23 mmol). The resulting solution was stirred at 25° C. for 2 d. After this time, the reaction was diluted with methylene chloride (25 mL) and was washed consecutively with a saturated ammonium chloride solution (1×25 mL), a saturated sodium bicarbonate solution (1×25 mL), water (1×25 mL) and a saturated aqueous sodium chloride solution (1×25 mL). The organics were then dried over magnesium sulfate, filtered, rinsed and concentrated in vacuo. Silica gel column chromatography (AnaLogix 8 g, 50-100% ethyl acetate/hexanes) afforded 3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(methyl-phenyl-amino)-6-oxo-6H-pyridazin-1-yl]-propionamide (39.4 mg, 44% over two steps) as a yellow solid; ES+-HRMS m/e calcd for C26H34N6O3 [M+H+] 479.2765, found 479.2764. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.04 (s, 3H) 1.05 (s, 3H) 1.06-1.11 (m, 1H) 1.16-1.33 (m, 1H) 1.37-1.74 (m, 7H) 1.84-1.99 (m, 1H) 2.17-2.30 (m, 1H) 3.33 (s, 3H) 3.88 (s, 2H) 4.66 (s, 1H) 5.39 (dd, J=10.5, 4.8 Hz, 1H) 6.40 (d, J=2.1 Hz, 1H) 6.71 (d, J=4.9 Hz, 1H) 6.96-7.03 (m, 2H) 7.03-7.11 (m, 1H) 7.22-7.31 (m, 2H) 7.51 (d, J=2.1 Hz, 1H) 7.82 (d, J=4.9 Hz, 1H) 10.55 (s, 1H).

Provenance & Evidence