Method of verifying the synthesis of organic molecules using nuclear magnetic resonance spectroscopy

A nuclear magnetic resonance (NMR) method for verifying a production of compounds within a library of organic compounds produced by combinatorial chemistry, the organic compounds generated by reacting a first class of first molecular structures with at least one additional second class of second molecular structures, with the compounds in the library being prepared having known first and second molecular structure content, wherein a first common structure class designation and first individual structure index designations are assigned to each of said first molecular structures and a second common structure class designation and second individual structure index designations are assigned to each of said second molecular structures, the method comprising the steps of:

• a) selecting a subset of library compounds which contains all of said first molecular structures and all of said second molecular structures;
• b) executing a two dimensional NMR pulse sequence to generate, after completion of the pulse sequence, a two dimensional NMR spectrum of each individual compound in said subset;
• c) adding and subtracting linear combinations of the NMR spectra resulting from step b) of individual compounds in said subset to generate an individual combined NMR spectrum for each of said first and said second molecular structures, each of said individual combined NMR spectra having enhanced intensity contributions from only one of said first and said second structures;
• d) uniquely assigning a signal group in said combined NMR spectra to individual ones of said first and said second molecular structures and to the associated first and second structure classes and indices;
• e) executing a two dimensional NMR pulse sequence to generate, upon completion of the pulse sequence, two dimensional spectra of a sample to examine an organic compound of the library other than those organic compounds used in the compound subset;
• f) analyzing said NMR spectra taken in step e) for a presence of all uniquely assigned signal groups;
• g) if said analyzing of a particular NMR spectrum indicates a presence of first and second molecular structures from the first and said second class corresponding to a particular organic compound of the library, characterizing that compound as TRUE;
• and
• h) repeating steps e) through g) on differing samples until all desired organic compounds in the library have been examined.