Results
Title

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

Authors

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

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.

Subjects

BOEHRINGER Ingelheim Pharmaceuticals Inc.; NON-small-cell lung carcinoma; MELTING points; DRUG synthesis; PROTEIN-tyrosine kinases

Publication

Molbank, 2020, Vol 2020, Issue 2, pM1134

ISSN

1422-8599

Publication type

Academic Journal

DOI

10.3390/M1134