反应详情

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).

1. concentrationthe reaction mixture is concentrated in vacuo
2. dissolutionThe residue is dissolved in DMF (1.5 mL)
3. stirringAfter stirring at room temperature for 5 h
4. washwashed with H2O and brine
5. dry with materialThe organic layer is dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue is purified by RP-HPLC