Triethylamine → 2-(4-Chloro-phenyl)-5-[3-chloro-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one

Participants

Reaction Steps

Dissolve 3-chloro-4-(2-pyrrolidin-1-yl-ethoxy)-phenylamine (0.20 g, 0.83 mmol) in CH2Cl2 (10.0 mL) and treat with trimethylaluminum (2.0M in hexanes, 0.6 mL, 1.20 mmol). Stir at room temperature for 15 min and add 2-(4-chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-one (0.22 g, 0.83 mmol) neat and stir the reaction at room temperature for 2 h. Carefully quench the mixture with saturated Rochelles salt solution and stir at room temperature for 1 h. Dilute with water and extract with CH2Cl2 (2×). Combine the organic portions and dry, filter and concentrate. Dissolve the residue in CH2Cl2, and treat with triethylamine (0.50 mL, 3.56 mmol) followed by methanesulfonyl chloride (0.05 mL, 0.65 mmol). Stir for 1 h at room temperature, dilute with water and extract with CH2Cl2 (2×). Combine the organic portions and dry, filter, and concentrate. Dissolve the residue in THF and treat with NaH (0.03 g, 0.75 mmol) and stir at room temperature for 18 h. Dilute the reaction with water and extract with CH2Cl2 (2×). Combine the organic portions, dry, filter, and concentrate. Purify the crude material by flash chromatography, using a gradient of 0% to 10% 2N NH3/MeOH in CH2Cl2, to give the title compound (80 mg, 37%). MS (ES+) 488.0 (M+1)+. 1H NMR (400 MHz, CDCl3): δ 7.93 (d, 2H, J=8.3 Hz), 7.45 (d, 2H, J=8.8 Hz), 7.39 (d, 1H, J=2.2 Hz), 7.22 (dd, 1H, J=8.8, 2.6 Hz), 6.97 (d, 1H, J=9.2 Hz), 4.22 (t, 2H, J=5.9 Hz), 4.07 (t, 2H, J=7.0 Hz), 3.28 (t, 2H, J=7.0 Hz), 3.01 (t, 2H, J=5.9 Hz), 2.73 (m 4H), 1.84 (m 4H).

Provenance & Evidence