Three-point variation of a gefinitib quinazoline core

Tetrahedron Letters

Volumn 50, Issue 14, 2009, Pages 1600-1602

  Harris, Craig S ^a   Hennequin, Laurent F ^a   Willerval, Olivier ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

Gefinitib; Mitsunobu alkylation; Quinazoline

Indexed keywords

GEFITINIB;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; METHODOLOGY;

EID: 60549101738     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2009.01.099     Document Type: Article

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23. 12 but for multi-parallel approaches where the end product is purified by mass-triggered preparative LC-MS using reverse-phase chromatography, the presence of large quantities of triphenylphosphine oxide can contaminate the final compounds depending on their polarity but more importantly 'drown' the mass detector resulting in loss of compound.
24. 3 (3.3 equiv) at 80 °C for 2 h (entry 7); (c) for the introduction of C4-aliphatic amines (entry 6), the residues were taken up in DMF and treated with the desired amine (3 equiv) at 80 °C for 2 h. The reaction mixtures were cooled to room temperature, filtered and purified directly by preparative LC-MS to afford the desired C4-substituted 6,7-bis-alkyoxyquinazolines (9) in acceptable overall yields.