Synthesis method of antineoplastic drug ribociclib intermediate

Abstract

The invention relates to a synthesis method of an antineoplastic drug ribociclib intermediate. The synthesis method includes the following steps that the electrophilic addition reaction is conducted on N,N-dimethylacrylamide and bromine to obtain N,N-dimethyl-2,3-dibromopropanamide, then under alkaline conditions, debromination is conducted to prepare N,N-dimethylpropiolamide, and at last the antineoplastic drug ribociclib intermediate is prepared by the reaction with N-cyclopentadienyl-2-chlorine-5-bromine-4-amidepyrimidinyl under the action of a catalyst. According to the synthesis method ofthe antineoplastic drug ribociclib intermediate, the preparation process is easy to operate, yield is high, the reaction route is short, three wastes are less, and industrial production is facilitated.

Description

technical field

[0001] The invention belongs to the field of synthesis of antineoplastic drug intermediates, in particular to a method for synthesizing an antineoplastic drug ribociclib intermediate. Background technique

[0002] Ribociclib (Ribociclib, I, with the following structure), developed by Novartis Pharmaceuticals, is a selective cyclin-dependent kinase 4 / 6 inhibitor, which can significantly prolong the estrogen receptor-positive, human epidermis in postmenopausal women. Progression-free survival in patients with growth factor receptor-2 negative advanced or metastatic breast cancer. In March 2017, it was approved for marketing by the US Food and Drug Administration (FDA). The product name is Kisqali. The oral dose is 600mg (3 tablets, 200mg per tablet) once a day. After 3 weeks of treatment, the drug is stopped for 1 week. Aromatase inhibitor letrozole and others are used in combination as an initial regimen based on endocrine therapy for the treatment of postmen...

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