Functionalization through lithiation of (S)-N-(1-phenylpropyl)-2-phenylquinoline-4-carboxamide. Application to the labeling with carbon-11 of NK-3 receptor antagonist SB 222200.
Lithiation of (S)-N-(1-phenylpropyl)-2-phenylquinoline-4-carboxamide with the complex n-BuLi/TMEDA (1/1 molar ratio) in THF at -60 degrees C for 5 h occurred selectively at the position 3 of the quinoline ring. This selectivity was shown by the absence of racemization of the stereogenic center and the formation of the corresponding functionalized quinolines in 59-74% yield by subsequent reaction with an electrophile at -60 degrees C for 1 h. The 3-trimethylstannyl derivative was subjected to a Stille reaction using methyl, phenyl, or thienyliodide to afford the alkyl or aryl quinolines in moderate to good yields. This methodology was successfully applied to the radiosynthesis of [11C]SB 222200 using methyl iodide labeled with carbon-11 (beta+ emitter, t1/2=20.4 min) for the in vivo study of NK-3 receptor by positron emission tomography (48-58% radiochemical yields from [11C]CH3I, decay corrected, 45 min total synthesis time).
Bennacef
Idriss
I
Groupe de Développements Méthodologiques en Tomographie par Emission de Positons, UMR CEA 2E, Université de Caen-Basse Normandie, Centre Cyceron, 15 Boulevard Henri Becquerel, 14070 Caen Cedex, France.
Perrio
Cécile
C
Lasne
Marie-Claire
MC
Barré
Louisa
L
D000577:Amides / Q000737:chemistry*; D000818:Animals; D002250:Carbon Radioisotopes; D002417:Cattle; D007553:Isotope Labeling / Q000379:methods; D008094:Lithium; D011804:Quinolines / Q000737:chemistry*; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors*
D000577:Amides; D002250:Carbon Radioisotopes; D011804:Quinolines; D018042:Receptors, Neurokinin-3; C109112:SB 222200; D008094:Lithium