Triethylamine → (+/-)-3-[2-(4-Hydroxy-piperidin-1-yl)-thiazol-4-yl]-3-[4-(7-methoxy-quinolin-8-yl)-[1,4]diazepan-1-yl]-1-(4-methyl-piperazin-1-yl)-propan-1-one

Participants

Reaction Steps

DMF (3.0 mL) was added to the product from step 2 (309 mg, 0.60 mmol), followed by N-methylpiperazine (0.08 mL, 0.72 mmol), and Et3N (0.17 mL, 1.20 mmol). HATU (274 mg, 0.72 mmol) was then added to the mixture, and the reaction was stirred for 2 h at room temperature. The solution was then diluted with CH2Cl2 and washed with H2O (4×50 mL), then brine. The organic was dried over MgSO4, filtered, and concentrated to give the crude. This was purified by silica gel chromatography (99:1 to 90:10 CH2Cl2:(9:1 MeOH:NH4OH)) and lyophilized from MeCN/H2O to give the product (122 mg, 34% yield) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.84 (dd, 1H, J=1.4, 4.2 Hz), 8.02 (dd, 1H, J=2.0, 8.0 Hz), 7.51 (d, 1H, J=8.8 Hz), 7.29 (d, 1H, J=8.8 Hz), 7.21 (dd, 1H, J=4.2, 8.2 Hz), 6.44 (s, 1H), 4.35 (bs, 1H), 3.95 (s, 3H), 3.95-3.76 (m, 2H), 3.67-3.45 (m, 7H), 3.24-2.78 (m, 8H), 2.42-2.33 (m, 2H), 2.28 (s, 3H), 2.32-2.10 (m, 5H), 2.02-1.92 (m, 4H), 1.68-1.58 (m, 2H). MS (ES) m/z 594.5 (M+H+).

Provenance & Evidence