Isopropyl iodide → 2-Cyano-4-[(spiro[2.5]oct-6-ylmethyl)amino]pyrimidine-5-carboxylic acid (4-benzyl-1-isopropylpiperidin-4-yl)amide

Participants

Reaction Steps

To a solution of 4-benzyl-4-({2-cyano-4-[(spiro[2.5]oct-6-ylmethyl)amino]-pyrimidine-5-carbonyl}amino)piperidine-1-carboxylic acid tert-butyl ester (0.14 mmol) in CH2Cl2 (1.5 mL) is added TFA (0.4 mL) at 0° C. After stirring at room temperature for 0.5 h, the reaction mixture is concentrated in vacuo. The residue is dissolved in DMF (1.5 mL) and treated with K2CO3 (0.35 mmol) and isopropyl iodide (0.28 mmol) at 0° C. After stirring at room temperature for 5 h, the reaction mixture is diluted with AcOEt and washed with H2O and brine. The organic layer is dried over Na2SO4, filtered, and concentrated in vacuo. The residue is purified by RP-HPLC to give the title compound; 1H NMR (CDCl3), δ: 0.18-0.26 (2H, m), 0.27-0.34 (2H, m), 0.91-0.99 (2H, m), 1.01-1.13 (6H, s), 1.17-1.33 (2H, m), 1.63-1.97 (7H, m), 2.15-2.40 (4H, m), 2.64-2.90 (3H, m), 3.15 (2H, s), 3.46 (2H, dd), 5.28 (1H, s), 7.02-7.10 (2H, m), 7.20-7.30 (3H, m), 8.05 (1H, s), 8.70 (1H, bs).

Provenance & Evidence