反应详情

To a 20 mL reaction vial was added propiolic acid (0.02 ml; 0.37 mmol; 1.10 eq.), bis(2-oxo-3-oxazolidinyl)phosphinic chloride (171.33 mg; 0.67 mmol; 2.00 eq.) and ethyl-diisopropyl-amine (0.28 ml; 1.68 mmol; 5.00 eq.) and 1.0 mL DMF. The reaction was stirred at rt for 1 h. Then (3S,4S)-4-{[6-Amino-5-(4-phenoxy-phenyl)-pyrimidin-4-ylamino]-methyl}-piperidin-3-ol hydrochloride (144.00 mg; 0.34 mmol; 1.00 eq.) in 1.0 mL DMF was added to the reaction mixture. The reaction mixture was stirred at rt overnight and then concentrated. The crude product was subjected to preparative HPLC. Fractions containing the desired product were combined and lyophilized overnight to afford 1-((3S,4S)-4-(((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)prop-2-yn-1-one as a white solid (35.2 mg, 18.6%). HPLC purity: 99%. MS: m/z=444 [M+H]+. 1H NMR (CD3OD) δ 8.24 (s, 1H), 7.10-7.46 (m, 9H), 4.36 (m, 2H), 4.00 (d, 1H), 3.74 (m, 1H), 3.52 (m, 1H), 3.25 (m, 1H), 3.00 (m, 1H), 2.64 (m, 1H), 1.76 (m, 2H), 1.30 (m, 1H).

1. customTo a 20 mL reaction
2. stirringThe reaction mixture was stirred at rt overnight
3. concentrationconcentrated
4. additionFractions containing the desired product
5. waitlyophilized overnight