Oxalyl chloride → 5-Amino-N-[2-({[(2,6-dibromophenyl)carbonyl]amino}methyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

関与物質

反応手順

To a solution of 2,6-dibromobenzoic acid (28 mg, 0.1 mmol) in anhydrous tetrahydrofuran (1 ml) was added anhydrous dimethylformamide (4 μl) followed by oxalyl chloride (100 μl of a 1 ml solution of 87 μl of oxalyl chloride in THF; 0.1 mmol). The mixture effervesced and was stirred under nitrogen for 45 minutes. A solution of 5-amino-N-[2-(aminomethyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide (25.3 mg, 0.07 mmole) in anhydrous tetrahydrofuran (0.5 ml) and diisopropylethylamine (52 μl, 0.3 mmol) was added. It was then stirred under nitrogen at 21° C. for 3 days. It was blown down, partitioned between dichloromethane (5 ml) and 2M hydrochloric acid (2 ml). The organic layer was blown down and the residue purified on a 5 g SPE silica cartridge. Elution with dichloromethane then cyclohexane:ethyl acetate (10:1), (5:1), (3:1), (2:1) (3 times) and finally (1:1) (3 times). The title product was eluted in the third (2:1) fraction and the first (1:1) fraction. These fractions were combined and evaporated to give the title product (39.6 mg).

情報源と証拠