Tris(hydroxymethyl)aminomethane → HCID 135537670, compound

Participants

Reaction Steps

To a mixture of 3-(5-hydroxymethyl-1H-indol-2-yl)-1H-thieno[3,2-c]pyrazole-5-carboxylic acid [159 mg, 0.507 mmol, Example 37], 1-hydroxybenzotriazole (116 mg, 0.858 mmol), PS-carbodiimide (1.2 mmol/g, 845 mg) in Dichloromethane (8 mL) and dimethyl formamide (2 mL) is stirred at room temperature for 25 minutes before addition of 3-ethoxypropylamine (45 mg, 0.436 mmol). After 4 h, PS-trisamine (4.03 mmol/g, 500 mg) is added and stirred for 6 hours. The reaction mixture is filtered and the resin washed under suction with Dichloromethane (3×15 mL). The filtrate is evaporated in vacuo. The crude is purified by chromatography on 10 g silica gel cartridge (ethyl acetate then 1% methanol in ethyl acetate) to give thick semi solid. It is redissolved in methanol and triturated with water to give 3-(5-hydroxymethyl-1H-indol-2-yl)-1H-thieno[3,2-c]pyrazole-5-carboxylic acid (3-ethoxy-propyl)-amide [30 mg, Example 39] as pale yellow solid; 1H NMR [(CD3)2SO)]: δ 13.490 (1H, s, NH), 11.56 (1H, NH, s), 8.70 (1H, t), 7.88 (1H, s), 7.51 (1H, s), 7.38 (1H, d), 7.10 (1H, s), 6.66 (1H, s), 5.01 (1H, t, OH), 4.55 (2H, HOCH2—), 3.44 (6H, m), 1.80 (2H), 1.12 (3H, t);

Provenance & Evidence