2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → HCID 67220208, compound

Participants

Reaction Steps

To a solution (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (97.1 mg, 0.451 mmol) in CH2Cl2 (2 mL) was added ethyl 2-ethoxyquinoline-1(2H)-carboxylate (EEDQ, 181.2 mg, 0.733 mmol) followed by (S)-tert-butyl 3-amino-6-(4-(2-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)phenyl)-1H-indazole-1-carboxylate (209.7 mg, 0.385 mmol) after about 5 min. The reaction mixture as allowed to stir at room temperature for 12 h and the solution was treated with EEDQ (79 mg, 0.365 mmol) and stirred for 48 h. The solution was treated with (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (60 mg, 0.279 mmol). After stirring a further 12 h the mixture was treated with MeOH (4 mL) followed by iPr2NEt (0.1 mL) and allowed to stir for 2 h. The solvent was removed in vacuo and the residue was purified by prep HPLC (CH3CN—H2O—NH4OAc) to give the title compound (197.4 mg, 69%) as a light yellow glass. 1H NMR (400 MHz, DMSO-d6) δ 11.90-11.95 (m, 1H), 11.13-11.20 (m, 1H), 8.33 (s, 1H), 8.09 (d, J=8 Hz, 1H), 7.88 (app d, J=8 Hz, 2H), 7.65-7.78 (m, 3H), 7.55-7.58 (m, 1H), 4.75-4.87 (m, 2H), 4.36-4.43 (m, 1H), 4.06-4.12 (m, 1H), 3.51-3.59 (m, 1H), 3.42-3.47 (m, 1H), 3.35-3.37 (m, 2H, partially obscured by H2O signal), 2.12-2.32 (m, 2H), 1.79-2.01 (m, 4H), 1.66 (s, 9H), 1.40 (s, 9H), 1.32 and 1.15 (s, 9H, rotamers). LCMS: Anal. Calcd. for C40H51N7O7: 741; found: 742 (M+H)+.

Provenance & Evidence