瑞博西力布的合成

Synthesis of Ribociclib

乳腺癌是女性患病率第一位的恶性肿瘤,其中激素受体阳性/人类表皮生长因子受体阴性乳腺癌患者占乳腺癌患者比例高达60%,临床急需有针对性的药物。瑞博西力布是一种口服的CDK4/6选择性抑制剂,被批准联合来曲唑用于一线治疗晚期或转移性HR阳性、HER2阴性乳腺癌。以4-氯-2-(甲硫基)嘧啶-5-乙醛和环戊基甘氨酸乙酯为起始原料,经过亲核取代、aldol缩合反应、氨解,甲硫基氧化、耦联,去保护合成瑞博西力布。目标产物经核磁共振氢谱、质谱得到确证。

Breast cancer is the most common malignant tumor in women.The proportion of breast cancer patients with hormone receptor positive/human epidermal growth factor receptor negative breast cancer accounts for 60%of breast cancer patients which called for urgently needed in clinic.Rebocilib is an oral selective inhibitor of CDK 4/6,which is approved to be combined with letrozole for the first-line treatment of advanced or metastatic HR positive and HER2 negative breast cancer.In this paper,reboxilib was synthesized from 4-chloro-2-(methylthio)pyrimidine-5-acetaldehyde and cyclopentylglycine ethyl ester through nucleophilic substitution,aldol condensation,ammonolysis,methylthio oxidation,coupling and deprotection.The target product was confirmed by 1H-NMR and MS.