Methods for carbon isotope labeling synthesis by transition metal-promoted carbonylation via ketene using diazo compounds and carbon-isotope monoxide
OwnerBengt Langstrom, Julien Barletta +2inventors
InventorsBengt Langstrom, Julien Barletta, Farhad Karimi, Hisashi Doi
Life of this patent
Estimating the term…
Abstract
Methods and reagents for transition metal-promoted carbonylation via diazo compounds using carbon-isotope labeled carbon monoxide are provided. The resultant carbon-isotope labeled compounds are useful as radiopharmaceuticals, especially for use in Positron Emission Tomography (PET). Associated kits for PET studies are also provided.
Claims25
A method for labeling synthesis, comprising:
- (a) Providing a high pressure reaction chamber having a liquid inlet and a gas inlet in a bottom surface thereof,
- (b) providing an diazo solution to be labeled mixed with a transition metal complex and an appropriate reagent,
- (c) introducing a carbon-isotope monoxide enriched gas-mixture into the reaction chamber via the gas inlet,
- (d) introducing at high pressure said diazo solution mixed with transition metal complex and said appropriate reagent into the reaction chamber via the liquid inlet,
- (e) waiting for a predetermined time while the labeling synthesis occur, and
- (f) collecting the labeled compound from the reaction chamber.
A method for radiocarbonylation comprising reaction of carbon-isotope monoxide with a compound of formula R1—CH—N2 to give a carbon-isotope labeled compound of formula R1—CH═C*═O, wherein wherein R1 is linear or cyclic alkyl, hydrogen or substituted alkyl, aryl or substituted aryl and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups.
A method for radiocarbonylation comprising reaction of carbon-isotope monoxide with a compound of formula (I) and a compound of formula (II):
- R1—CH—N2 (I)
- R2R3NH (II),
- to give a labeled compound of formula (IIa):
- wherein R1 is linear or cyclic alkyl, hydrogen or substituted alkyl, aryl or substituted aryl and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups and R2 and R3 are independently linear or cyclic lower alkyl or substituted alkyl, hydrogen, aryl or substituted aryl, and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups.
A method for radiocarbonylation comprising reaction of carbon-isotope monoxide with a compound of formula (I) and a compound of formula (III):
- R1—CH—N2 (I)
- R2OH (III),
- to give a labeled compound of formula (IIIa):
- wherein R1 is linear or cyclic alkyl, hydrogen or substituted alkyl, aryl or substituted aryl and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups and R2 and R3 are independently linear or cyclic lower alkyl or substituted alkyl, hydrogen, aryl or substituted aryl, and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups.
A method for radiocarbonylation comprising reaction of carbon-isotope monoxide with a compound of formula (I) and a compound of formula (IV)
- R1—CH—N2 (I)
- R2SH (IV),
- to give a labeled compound of formula (IVa):
- wherein R1 is linear or cyclic alkyl, hydrogen or substituted alkyl, aryl or substituted aryl and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups and R2 and R3 are independently linear or cyclic lower alkyl or substituted alkyl, hydrogen, aryl or substituted aryl, and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups.
A method for radiocarbonylation comprising reaction of carbon-isotope monoxide with a compound of formula (I) and a compound of formula (VI):
- R1—CH—N2 (I)
- to give a labeled compound of formula (VIa):
- wherein R1 is linear or cyclic alkyl, hydrogen or substituted alkyl, aryl or substituted aryl and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups and R2, R3, R4 and R5 are independently linear or cyclic lower alkyl or substituted alkyl, hydrogen, aryl or substituted aryl, and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups.
A method for radiocarbonylation comprising reaction of carbon-isotope monoxide with a compound of formula (I) and a compound of formula (VII):
- R1—CH—N2 (I)
- to give a labeled compound of formula (VIIa):
- wherein R1 is linear or cyclic alkyl, hydrogen or substituted alkyl, aryl or substituted aryl and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups and R2, R3, R4 and R5 are independently linear or cyclic lower alkyl or substituted alkyl, hydrogen, aryl or substituted aryl, and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups.
A method for radiocarbonylation comprising reaction of carbon-isotope monoxide with a compound of formula (I) and a compound of formula (VIII):
- R1—CH—N2 (I)
- R2≡R3 (VIII),
- to give a labeled compound of formula (VIIIa):
- wherein R1 is linear or cyclic alkyl, hydrogen or substituted alkyl, aryl or substituted aryl and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups and R2, R3, R4 and R5 are independently linear or cyclic lower alkyl or substituted alkyl, hydrogen, aryl or substituted aryl, and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups.
A method for radiocarbonylation comprising reaction of carbon-isotope monoxide with a compound of formula (I) and a compound of formula (IX):
- R1—CH—N2 (I)
- to give a labeled compound of formula (IXa):
- wherein R1 is linear or cyclic alkyl, hydrogen or substituted alkyl, aryl or substituted aryl and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups and R2, R3 and R4 are independently linear or cyclic lower alkyl or substituted alkyl, hydrogen, aryl or substituted aryl, and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups.
A method for radiocarbonylation comprising reaction of carbon-isotope monoxide with a compound of formula (I) and a compound of formula (X):
- R1—CH—N2 (I)
- to give a labeled compound of formula (Xa):
- wherein R1 is linear or cyclic alkyl, hydrogen or substituted alkyl, aryl or substituted aryl and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups and R2 is independently linear or cyclic lower alkyl or substituted alkyl, hydrogen, aryl or substituted aryl, and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups.
A kit for PET study comprising a carbon-isotope labeled compound selected from
- wherein R1 is linear or cyclic alkyl, hydrogen or substituted alkyl, aryl or substituted aryl and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups and R2, R3, R4 and R5 are independently linear or cyclic lower alkyl or substituted alkyl, hydrogen, aryl or substituted aryl, and may contain carbonyl, hydroxy, thiol, halogen, nitrile, isonitrile, cyanate, isocyanate, thiocyanate, isothiocyanate functional groups.
Dependencies are inferred from the claim text.