Ethyl isocyanate → 1-{4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-3-ethyl-urea

関与物質

反応条件

反応手順

Dissolve 4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-benzylamine (0.35 g, 0.93 mmol) in tetrahydrofuran (6 mL). Add isocyanato-ethane (1 eq., 0.06 g, 0.84 mmol). Add 4-(dimethylamino)pyridine (0.05 eq., 0.005 g, 0.043 mmol). Heat at 50° C. for 17 hr. Purify by normal phase chromatography with eluent 4% 7N ammonia-methanol/ethyl acetate to give 1-{4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-benzyl}-3-ethyl-urea (0.252 g, 62%). MS (ES): m/z=449.3[M+H]. Dissolve (0.252 g, 0.56 mmol) in acetonitrile (1 mL) and water (4 mL). Add aq. 1 N HCl (1 eq., 0.56 mmol, 0.56 mL). Freeze the solution to −78° C. in a dry-ice/acetone bath. Place the solution in the lyophilizer for 48 hr. to give the title compound (0.250 g, 97% yield). MS (ES): m/z=449.3 [M+H].

情報源と証拠