Study and characterization of crystalline hydrate/polymorph forms of 5,11-dihydro-11-ethyl-5-methyl-8-(2-(1-oxido-4-quinolinyl)ethyl-6H-dipyrido(3,2-B:2',3'-E)(1,4)diazepin-6-one by solid-state NMR and solution NMR.
A novel inhibitor of reverse transcriptase was studied by solid-state NMR. Three phases of the compound were examined which included the dihydrate and two anhydrous polymorphs (Form I and Form III). By correlating (1)H and (13)C solution NMR with the solid-state (13)C NMR CP/MAS and CPPI spectral editing experiments, comparative (13)C assignments were made for each phase. Polymorphs of Form I and Form III and the dihydrate were easily distinguished based upon chemical shift patterns of the carbon resonances. The (1)H spin-lattice relaxation times were also measured for each phase which provided information on the mobility and relative crystallinity. The (13)C ssNMR spectrum of Form I showed the presence of a minor component identified as the dihydrate. Weight/percent quantitation of major and minor components in Form I was obtained from integrated intensities of a 50:50 mixture containing weighed amounts of Form I and the pure dihydrate. Comparison of the ssNMR and X-ray powder diffraction techniques is discussed.
Gonnella
N C
NC
Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Rd., Ridgefield, CT 06877, United States. nina.gonnella@boehringer-ingelheim.com
Smoliga
John A
JA
Campbell
Scot
S
Busacca
Carl A
CA
Cerreta
Michael
M
Varsolona
Richard
R
Norwood
Daniel L
DL
D001381:Azepines / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D033362:Powder Diffraction; D011725:Pyridines / Q000737:chemistry*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry
C548654:5,11-dihydro-11-ethyl-5-methyl-8-(2-(1-oxido-4-quinolinyl)ethyl)-6H-dipyrido(3,2-B,2',3'-E)(1,4)diazepin-6-one; D001381:Azepines; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D014867:Water