반응 단계
To a suspension of N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride 18 (1.22 g, 4 mmol) in dry chloroform (50 mL) was added triethylamine (0.72 mL) at room temperature. The clear solution obtained was then cooled to −10° C. and a solution of triphosgene (0.712 g, 2.4 mmole) in dry chloroform (10 mL) was added dropwise into a reaction mixture at 0° C. After being stirred for 30 min, the reaction mixture was evaporated to dryness under reduced pressure. The solid residue was triturated with dry THF (100 ml), filtered, and washed with small amount of THF. The combined filtrate and washings was evaporated to dryness to give the crude isocyanate 19, which was then dissolved in dry DMF (5 mL) and added dropwise to a solution of N1-(6-methoxy-2-methylquinolin-4-yl)benzene-1,3-diamine (0.56 g, 2 mmol) in dry DMF (10 mL) containing Et3N (1 mL). After being stirred for 5 h at room temperature, the solid separated was filtered and washed with dry DMF. The filtrate was evaporated to dryness in vacuo. The residue was purified by column chromatography using CHCl3/MeOH (100:3 v/v) as an eluent. The fractions containing the main product were combined and evaporated to dryness and the residue was recrystallized from CHCl3 to give BO-1547 (0.87 g, 81%); mp 225-227° C.; 1H NMR (DMSO-d6) δ 2.58 (3H, s, Me), 3.68-3.70 (8H, m, CH2), 3.97 (3H, s, OMe), 6.73-6.69 (3H, m, Ar—H), 7.03 (1H, d, J=7.6 Hz, Ar—H), 7.28 (2H, d, J=9.0 Hz, Ar—H), 7.35 (1H, d, J=7.7 Hz, Ar—H), 7.44 (1H, t, J=8.0 Hz, Ar—H), 7.64-7.62 (1H, m, Ar—H), 7.71 (1H, s, Ar—H), 7.93 (1H, d, J=9.1 Hz, Ar—H), 8.09 (1H, s, Ar—H), 8.84 (1H, s, NH, Exchangeable), 9.31 (1H, s, NH, Exchangeable), 10.49 (1H, s, NH, Exchangeable); ESI-HRMS calcd for C28H29Cl2N5O2 m/z 538.4682 (M+H). found 538.2451 (M+H).
