Diisopropylethylamine → N-(5-((6-methoxy-7-(piperidin-4-ylmethoxy)quinolin-4-yl)oxy)pyridin-2-yl)-4-phenylthiazole-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 4-(((4-((6-aminopyridin-3-yl)oxy)-6-methoxyquinolin-7-yl)oxy)methyl)piperidine-1-carboxylate (70 mg, 0.14 mmol), 4-phenylthiazole-2-carboxylic acid (46 mg, 0.21 mmol), DIPEA (56 mg, 0.43 mmol) and HATU (110 mg, 0.29 mmol) in dry DMF (5 mL) was stirred for 72 h at 55° C. The solution was diluted with EtOAc (150 mL) and washed twice with aq.NaHCO3-solution and once with brine. The residue was dissolved in 50% TFA in DCM (5 mL) and stirred for 2 h at RT. The mixture was concentrated under reduced pressure. The residue was purified by reverse phase RP-HPLC (column: C18), using H2O and ACN as eluents. The desired fractions were lyophilized to yield the title compound X14 (25 mg, 30%) as a white powder. 1H NMR (400 MHz, d6-DMSO, 300K) δ 1.25 (m, 2H), 1.76 (d, J=12.0 Hz, 2H), 1.95 (m, 1H), 2.55 (t, J=11.0 Hz, 2H), 3.00 (d, J=12.0 Hz, 2H), 3.94 (s, 3H), 3.99 (d, J=6.3 Hz, 2H), 6.58 (d, J=5.2 Hz, 1H), 7.41 (m, 2H), 7.51 (m, 3H), 7.90 (dd, J=2.9 Hz, J=9.0 Hz, 1H), 8.17 (d, J=7.4 Hz, 2H), 8.29 (d, J=9.0 Hz, 1H), 8.48 (d, J=2.9 Hz, 1H), 8.50 (d, J=5.2 Hz, 1H), 8.55 (s, 1H). MS (ES) C3H29N5O4S requires: 567. Found: 568 (M+H)+.

Provenance & Evidence