5-Amino-1-(2-pyrrolidin-1-ylethyl)indole → 2-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid [1-(2-pyrrolidin-1-yl-ethyl)-1H-indol-5-yl]-amide

Participants

Reaction Conditions

Reaction Steps

Dissolve 1-(2-pyrrolidin-1-yl-ethyl)-1H-indol-5-ylamine (247 mg, 1.08 mmol) in CH2Cl2 (5 mL), cool to 0° C., and treat with a solution of trimethylaluminum (2.0 M in hexanes, 0.7 mL, 1.40 mmol). Stir the solution at 0° C. for 15 min and then at room temperature for 30 min. Add 2-(4-chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-one (272 mg, 1.02 mmol) neat and stir the reaction at room temperature overnight. Carefully quench the mixture with saturated Rochelles salt solution (5 mL) and stir at room temperature for 1 h. Dilute with additional saturated Rochelles salt solution (10 mL) and extract with CH2Cl2 (3×20 mL). Combine the organic portions, dry, filter, and concentrate under vacuum. Triturate the crude solid with diethyl ether to give the title compound as a white powder (400 mg, 75%). MS (ES+) 495.1 (M+1)+MS (ES−) 493.2 (M−1)−. 1H NMR (400 MHz, DMSO-d6): δ 10.78 (s, 1H), 8.01 (d, 2H, J=8.3 Hz), 7.92 (s, 1H), 7.60 (d, 2H, J=8.8 Hz), 7.46 (d, 1H, J=8.8 Hz), 7.40 (d, 1H, J=3.1 Hz), 7.34 (dd, 1H, J=8.8, 1.8 Hz), 6.41 (d, 1H, J=3.1 Hz), 5.84 (m, 1H), 4.26 (t, 2H, J=6.6 Hz), 3.91 (q, 2H, J=5.3 Hz), 3.21 (t, 2H, J=5.9 Hz), 2.78 (t, 2H, J=6.8 Hz), 2.46 (s, 4H), 1.65 (m, 4H).

Provenance & Evidence