An improved one-pot procedure for the preparation of [11C-carbonyl]-WAY100635.
A simple one-pot procedure for the preparation of [11C-carbonyl]-WAY100635, a potent 5HT1A receptor antagonist, was developed. The procedure involves the trapping of 11CO2 in a tetrahydrofuran (THF) solution of cyclohexylmagnesium chloride, elimination of excess Grignard reagents with anhydrous HCl, reaction with SOCl2, and the reaction of the resulting acid chloride with WAY100634 (2 mg) and triethylamine (20 microL) in THF. The total synthesis time is 45 min. Starting from 1326 +/- 173 mCi of 11CO2, the average amount of [11C-carbonyl]-WAY100635 (n = 40) at end-of-synthesis (EOS) was 30 +/- 13 mCi (2.3% radiochemical yield), or 148 +/- 61 mCi (11%) at end-of-bombardment (EOB). The radiochemical purity was >99%, and the specific activity was 3.6 +/- 1.9 Ci/micromol (EOS, n = 40), or 21.3 +/- 9.8 Ci/micromol at EOB. This method is reliable and flexible for routine clinical studies.
Hwang
D R
DR
Department of Medicine and Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. hwang@neuron.cpmc.columbia.edu
Simpson
N R
NR
Montoya
J
J
Man
J J
JJ
Laruelle
M
M
D002245:Carbon Dioxide / Q000737:chemistry; D002250:Carbon Radioisotopes; D005663:Furans / Q000737:chemistry; D007553:Isotope Labeling / Q000295:instrumentation / Q000379:methods; D010879:Piperazines / Q000138:chemical synthesis*; D011725:Pyridines / Q000138:chemical synthesis*; D011854:Radiochemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D012702:Serotonin Antagonists / Q000138:chemical synthesis*
D002250:Carbon Radioisotopes; D005663:Furans; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; D012702:Serotonin Antagonists; D002245:Carbon Dioxide; C018674:tetrahydrofuran; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide