Ethyl 2-bromo-1,3-thiazole-4-carboxylate → [6-Chloro-7-(2-chloro-5-methoxy-phenyl)-benzo[1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine

Participants

Reaction Steps

6-chloro-7-(2-chloro-5-methoxy-phenyl)benzo[1,2,4]triazin-3-ylamine designated on the reaction scheme (CCLXXVI) as compound 19 (54 mg, 68%) was prepared from compound 18 and 2-chloro-5-methoxyphenylboronic acid according to the above-described coupling procedure. The crude product was purified by silica gel column chromatography (Rf=0.41, EtOAc/hexanes 50:50). The title compound (CCLXXV) was prepared from compound 19 and 1-[2-(4-bromo-phenoxy)-ethyl]-pyrrolidine following the above-described coupling procedure, followed by demethylation. The coupling product was purified by reverse phase preparative HPLC to give [6-chloro-7-(2-chloro-5-methoxy-phenyl)-benzo[1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine (28.7 mg, 27%). Deprotection of the methoxy group with BBr3 (22 μl, 0.23 mmol) in 2 mL CH2Cl2 at room temperature yielded 4-chloro-3-{6-chloro-3-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylamino]-benzo[1,2,4]triazin-7-yl}-phenol, which was purified by reverse phase preparative HPLC and converted to the free amine to give a brown solid (13 mg, 57%). 1H NMR DMSO-d6: δ 1.68 (m, 4H), 2.50-2.55 (m, 4H), 2.79 (t, J=5.9 Hz, 2H), 4.07 (t, J=5.9, 2H), 7.07 (d, J=9.0 Hz, 1H), 6.77 (d, J=2.8, 1H), 6.84 (dd, J=8.8 Hz, J=2.8 Hz, 1H), 6.98 (d, J=9.0 Hz, 2H), 7.32 (d, J=8.8, 1H), 7.85 (d, J=9.0 Hz, 2H), 7.90 (s, 1H), 8.22 (s, 1H), 10.90 (br s, 1H). MS (ESI+) m/z=496.

Provenance & Evidence