Reaction Steps
Combine 3,4-dichlorocinnamic acid (0.083 g, 0.381 mmol), CH2Cl2 (5.0 mL), and DMF (3 drops) with stirring. Add oxalyl chloride (0.10 mL, 1.14 mmol) and stir the mixture for 3 h at room temperature. Concentrate the mixture in vacuo, add hexane (approximately 10 mL), re-concentrate in vacuo, and add CH2Cl2 (5.0 mL). Transfer the mixture to a 40 mL reaction vial and add a mixture of 2-(3-dimethylamino-pyrrolidin-1-yl)-benzothiazol-6-ylamine (0.100 g, 0.381 mmol) (Example 1, step 3) in CH2Cl2 (5.0 mL). Shake the reaction vial overnight at room temperature. Dilute the reaction mixture with CH2Cl2 (30 mL), wash with saturated NaHCO3 (aqueous) (2×25 mL), dry over sodium sulfate, filter, and concentrate in vacuo. Purify the residue using silica gel chromatography (12 g column, 5-15% MeOH/CH2Cl2 over 45 min) to yield a yellow residue. Dilute the residue with CH2Cl2 (25 mL) and wash with 1 M NaOH (25 mL). Filter a yellow solid which precipitates in the separatory funnel. Concentrate the mother liquor in vacuo and filter, washing with cold CH2Cl2 to obtain a second crop. Combine the precipitate from the separatory funnel, and the second crop, to afford the title compound (57 mg, 32%). mass spectrum (m/e): 461.2 [M+1], 459.2 [M−1]. 1H NMR (400 MHz, CDCl3): δ8.31 (d, 1H, J=1.6 Hz), 7.65 (d, 1H, J=15.6 Hz), 7.64 (m, 1H), 7.52 (d, 1H, J=8.4 Hz), 7.46 (d, 1H, J=8.4 Hz), 7.37 (m, 1H), 7.35 (m, 1H), 7.16 (dd, 1H, J=8.8, 2.4 Hz), 6.53 (d, 1H, J=15.6 Hz), 3.86 (t, 1H, J=9.2 Hz), 3.74 (t, 1H, J=9.2 Hz), 3.56 (m, 1H), 3.50-3.42 (m, 1H), 2.98 (m, 1H), 2.36 (s, 6H), 2.29 (m, 1H), 2.07 (m, 1H).
