TY - JOUR
T1 - Acid-Catalyzed Synthesis of Isatoic Anhydride-8-Secondary Amides Enables IASA Transformations for Medicinal Chemistry
AU - Gondi, Sudershan R.
AU - Shaik, Althaf
AU - Westover, Kenneth D.
N1 - Funding Information:
The authors declare the following competing financial interest(s): K.D.W has received consulting fees from Sanofi Oncology and is a member of the SAB for Vibliome Therapeutics. He also receives research funding from Revolution Medicines. K.D.W. declares that none of these relationships are directly or indirectly related to the content of this manuscript.
Publisher Copyright:
© 2021 American Chemical Society
PY - 2022/1/7
Y1 - 2022/1/7
N2 - Quinazolin-dione-N-3-alklyl derivatives are the core scaffolds for several categories of bioactive small molecules, but current synthetic methods are costly, involve environmental hazards, and are not uniformly scalable. Here, we report an inexpensive, flexible, and scalable method for the one-pot synthesis of substituted quinazolin-dione-N-3-alkyls (isomers of isatoic-8-secondary amides (IASAs)) from isatin that take advantage of in situ capture of imidic acid under acidic conditions. We further show that this method can be used for the synthesis of a wide variety of derivatives with medicinal uses.
AB - Quinazolin-dione-N-3-alklyl derivatives are the core scaffolds for several categories of bioactive small molecules, but current synthetic methods are costly, involve environmental hazards, and are not uniformly scalable. Here, we report an inexpensive, flexible, and scalable method for the one-pot synthesis of substituted quinazolin-dione-N-3-alkyls (isomers of isatoic-8-secondary amides (IASAs)) from isatin that take advantage of in situ capture of imidic acid under acidic conditions. We further show that this method can be used for the synthesis of a wide variety of derivatives with medicinal uses.
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U2 - 10.1021/acs.joc.1c02036
DO - 10.1021/acs.joc.1c02036
M3 - Article
C2 - 34962124
AN - SCOPUS:85122405064
SN - 0022-3263
VL - 87
SP - 125
EP - 136
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 1
ER -