Diisopropylethylamine → 3-{[3-(3-Fluoro-pyridin-4-yl)-5-methyl isoxazole-4-carbonyl]-amino}cyclo-hexanecarboxylic acid ethy ester

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Reaction Steps

Dissolve 3-methoxycarbonylamino-cyclohexanecarboxylic acid ethyl ester (513 mg, 2.24 mmol) in dry dichloromethane (10 mL). Add iodotrimethylsilane (0.48 mL, 3.4 mmol) and stir the resulting mixture for 2.5 h at ambient temperature. Quench with methanol (5 mL) and concentrate in vacuo. Concentrate the resulting residue twice from diethyl ether and use the crude amine salt directly without purification. Combine this amine salt with 3-(3-fluoro-pyridin-4-yl)-5-methyl-isoxazole-4-carboxylic acid (500 mg, 2.24 mmol),1-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide hydrochloride (430 mg, 2.24 mmol), 1-hydroxy-7-azabenzo-triazole (305 mg, 2.24 mmol), and N,N-diisopropylethyl amine (2.0 mL, 11.5 mmol) in N,N-dimethylformamide (15 mL) and stir overnight at ambient temperature. Concentrate the mixture in vacuo and take up in water and extract with dichloromethane. Dry the combined extracts over sodium sulfate and concentrate in vacuo. Elute the resulting residue over silica gel using methanol/dichloromethane which to give 720 mg (86%) of the desired amide as a white solid. MS(ES): (M+1)+ 376.2, 377.3 m/z.

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