Synthesis and Spectral Characterization of 4,7-Dichloro-6-nitroquinazoline
Thi Ngoc Nguyen, , , , , , , May-2020, In: Molbank, 2020 (2), M1134
Overview
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 |