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Synthesis and Spectral Characterization of 4,7-Dichloro-6-nitroquinazoline
Home Research Publications Synthesis and Spectral Characterization of 4,7-Dichloro-6-nitroquinazoline

Synthesis and Spectral Characterization of 4,7-Dichloro-6-nitroquinazoline

Thi Ngoc Nguyen, Nguyen Trieu Trinh , Dinh Luyen Nguyen , Van Giang Nguyen , Nguyet Suong Huyen Dao , Thi Huong Tran , Van Hai Nguyen , May-2020, In: Molbank, 2020 (2), M1134

Overview

  • Thi Ngoc Nguyen
  • Nguyen Trieu Trinh
  • Dinh Luyen Nguyen
  • Van Giang Nguyen
  • Nguyet Suong Huyen Dao
  • Thi Huong Tran
  • Van Hai Nguyen

Abstract:

Afatinib is a 4-anilinoquinazoline tyrosine kinase inhibitor (TKI) in the form of a dimaleate salt which is indicated for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). The most scalable route for the synthesis of this drug was reported in two Boehringer Ingelheim patents, in which the title compound, 4,7-dichloro-6-nitroquinazoline (IV), is an important intermediate. Compound IV is also present in a number of synthetic pathways for various 4,7-disubstituted quinazoline derivatives displaying high therapeutic potential. However, no detailed characterization of this popular compound has been reported, possibly due to its high instability. In this paper, IV was prepared in an overall yield of 56.1% by a 3-step process (condensation, nitration, and chlorination) from 2-amino-4-chlorobenzoic acid (I). The target compound has been for the first time fully characterized by melting point, mass-spectrometry, FT-IR, 1H-NMR and 13C-NMR spectroscopies.

Keyword(s): afatinib; 2-amino-4-chlorobenzoic acid; 4,7-dichloro-6-nitroquinazoline; quinazoline

Journal Molbank
Volume 2020 (2)
Issue number M1134
Publication status Published - May-2020
ISBN 1422-8599