Linked Life Data

19296668

Source:http://linkedlifedata.com/resource/pubmed/id/19296668

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-5-11
pubmed:abstractText
A solid-phase organic synthesis method has been developed for the preparation of trisubstituted pyrimidin-6-one carboxylic acids 12, which allows elaboration to a 3-dimensional combinatorial library. Three substituents are introduced by initial Knoevenagel condensation of an aldehyde and malonate ester resin 7 to give resin bound 1. Cyclization of 1 with an N-substituted amidine 10, oxidation, and cleavage afforded pyrimidinone 12. The initial solid-phase reaction sequence was followed by gel-phase (19)FNMR and direct-cleavage (1)H NMR of intermediate resins to determine the optimal conditions. The scope of the method for library production was determined by investigation of a 3 x 4 pilot library of twelve compounds. Cyclocondensation of N-methylamidines and 7 followed by CAN oxidation gave mixtures of the resin bound pyrimidin-6-one 11 and the regioisomeric pyrimidin-4-one 15, which after cleavage from the resin afforded a nearly 1:1 mixture of pyrimidin-6-one and pyrimidin-4-one carboxylic acids 12 and 16, respectively. The regiochemical assignment was confirmed by ROESY1D and gHMBC NMR experiments. A library was prepared using 8 aldehydes, 3 nitriles, and 4 amines to give a full combinatorial set of 96 pyrimidinones 12. Confirmation of structural identity and purity was carried out by LCMS using coupled ELS detection and by high-throughput flow (1)H NMR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1520-4774
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
469-80
pubmed:meshHeading
pubmed:articleTitle
Parallel solid-phase synthesis and high-throughput 1H NMR evaluation of a 96-member 1,2,4-trisubstituted-pyrimidin-6-one-5-carboxylic acid library.
pubmed:affiliation
Pfizer Inc., Global Research and Development, Medicinal Chemistry, Chesterfield, Missouri 63017, USA. brucehamper@gmail.com
pubmed:publicationType
Journal Article