Solid-phase synthesis of 2,4-diaminoquinazoline libraries.
A series of libraries containing the 2,4-diaminoquinazoline ring system were prepared, starting from polymer-bound amines. The key steps included reaction of the support-bound amine with 6,7-dimethoxy-2,4-dichloroquinazoline, followed by displacement of the second chlorine with an amine and subsequent TFA-mediated cleavage of the product from the support. When a symmetrical or unsymmetrical diamine was used in the displacement step, the free amine could be acylated with an activated acid to generate another set of compounds. The optimization of conditions for the reductive amination and displacement steps will be discussed as well as the final choice of resin for library production. In addition, quality control methods for library analysis is also described.
Dener
J M
JM
ChemRx Advanced Technologies, A Discovery Partners International Company, 385 Oyster Point Boulevard, Suite 1, South San Francisco, CA 94080, USA. dener@chemrx.com
Lease
T G
TG
Novack
A R
AR
Plunkett
M J
MJ
Hocker
M D
MD
Fantauzzi
P P
PP
D002626:Chemistry, Pharmaceutical; D020650:Combinatorial Chemistry Techniques; D005493:Folic Acid Antagonists / Q000138:chemical synthesis; D011799:Quinazolines / Q000138:chemical synthesis*; D012117:Resins, Synthetic; D012997:Solvents
D005493:Folic Acid Antagonists; D011799:Quinazolines; D012117:Resins, Synthetic; D012997:Solvents; C013474:2,4-diaminoquinazoline