An Improved Synthesis Route of Molnupiravir and its Key Impurities
Abstrak
This paper aims to improve the synthetic process of molnupiravir based on previously reported synthetic routes. The route begins with uracil (ML-2), which is protected with an isopropyl group to yield ML-3 (Step 1), followed by an esterification and a triazolation reaction (Steps 2 and 3) to produce ML-5, which, via a hydroxylation reaction and deprotection (Steps 4 and 5), gives the target product ML-1. Nuclear magnetic resonance (1H NMR) and mass spectra were used for chemical structure identification. There are mainly the following improvements, including: (1) replacing the separate addition of acetone and concentrated H2SO4 with 2,2-dimethoxypropane and catalytic p-toluenesulfonic acid monohydrate in Step 1, simplifying the workup operation and reducing the dosage of reaction solvent. (2) Optimize the synthesis conditions of ML-5, reduce the formation of impurities, and improve the purity of the crude product from 43.12 to 85.21%. (3) Three impurities were isolated, two of which are new compounds. This article lays a foundation to obtain molnupiravir with controllable quality and a stable process for the treatment of coronavirus disease 2019.
Penulis (5)
Guojing Li
Zhihao Du
Xin Gao
Dongsheng Chen
Yu Liu
Akses Cepat
- Tahun Terbit
- 2025
- Bahasa
- en
- Sumber Database
- CrossRef
- DOI
- 10.1055/a-2735-5050
- Akses
- Open Access ✓