Diisopropylethylamine → HCID 58790289, compound

Participants

Reaction Steps

To a solution of the amine 9 (80 mg, 0.235 mmol), acid 35 (64 mg, 0.235 mmol) and BOP (114.6 mg, 0.254 mmol) in DMF (2.4 mL) was added DIPEA (0.164 mL, 0.941 mmol) and the mixture stirred 2 h at room temperature. EtOAc (100 mL) and water (50 mL) were added and the mixture was filtered through a paper filter. The organic phase was collected, washed with water (50 mL), brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (eluent EtOAc/MeOH 7:1) giving tert-butyl 3-(3-(3-fluoro-4-(2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenylamino)-3-oxopropanamido)pyrrolidine-1-carboxylate (35a, 29.7 mg, 21% yield) as a glassy solid. MS (m/z): 595.1 (M+H). This material was dissolved in a solution of TFA (0.5 mL) and DCM (0.5 mL) and stirred for 1 h at room temperature. The reaction mixture was concentrated under reduced pressure, water was added to the residue and the mixture was lyophilized. The resultant solid was purified by preparative HPLC (Aquasil C-18 column, gradient: MeOH 60% to MeOH 95% in water) to afford the title compound 36 as tris-trifluoroacetate salt (13.9 mg, 35%), creamy fluffy solid. 1H NMR (DMSO-d6) δ (ppm): 10.51 (s, 1H), 8.81 (bs, 1H), 8.72 (bs, 1H), 8.57 (d, J=5.4 Hz, 1H), 8.47 (d, J=6.3 Hz, 1H), 7.86 (m, 1H), 7.58 (s, 1H), 7.50 (t, J=9.0 Hz, 1H), 7.40 (m, 1H), 7.31 (s, 1H), 6.76 (d, J=5.4 Hz, 1H), 4.29 (m, 1H), 3.82 (s, 3H), 3.40 (m, 1H), 3.36-3.20 (m, 4H), 2.99 (m, 1H), 2.16 (m, 1H), 1.85 (m, 1H). MS (m/z): 495.2 (M+H).

Provenance & Evidence