112181-38-1Relevant articles and documents
An efficient and practical synthesis of [2-11C]indole via superfast nucleophilic [11C]cyanation and RANEY Nickel catalyzed reductive cyclization
Lee, So Jeong,Fowler, Joanna S.,Alexoff, David,Schueller, Michael,Kim, Dohyun,Nauth, Alexander,Weber, Carina,Kim, Sung Won,Hooker, Jacob M.,Ma, Ling,Qu, Wenchao
, p. 11235 - 11243 (2015)
A rapid method for the synthesis of carbon-11 radiolabeled indole was developed using a sub-nanomolar quantity of no-carrier-added [11C]cyanide as radio-precursor. Based upon a reported synthesis of 2-(2-nitrophenyl)acetonitrile (2), a highly reactive substrate 2-nitrobenzyl bromide (1) was evaluated for nucleophilic [11C]cyanation. Additionally, related reaction conditions were explored with the goal of obtaining of highly reactive 2-(2-nitrophenyl)-[1-11C]acetonitrile ([11C]-2) while inhibiting its rapid conversion to 2,3-bis(2-nitrophenyl)-[1-11C]propanenitrile ([11C]-3). Next, a RANEY Nickel catalyzed reductive cyclization method was utilized for synthesizing the desired [2-11C]indole with hydrazinium monoformate as the active reducing agent. Extensive and iterative screening of basicity, temperature and stoichiometry was required to overcome the large stoichiometry bias that favored 2-nitrobenzylbromide (1) over [11C]cyanide, which both caused further alkylation of the desired nitrile and poisoned the RANEY Nickel catalyst. The result is an efficient two-step, streamlined method to reliably synthesize [2-11C]indole with an entire radiochemical yield of 21 ± 2.2% (n = 5, ranging from 18-24%). The radiochemical purity of the final product was >98% and specific activity was 176 ± 24.8 GBq μmol-1 (n = 5, ranging from 141-204 GBq μmol-1). The total radiosynthesis time including product purification by semi-preparative HPLC was 50-55 min from end of cyclotron bombardment.
Syntheses of two isotopically labeled CB1 receptor antagonists
Czeskis, Boris A.
experimental part, p. 171 - 176 (2012/07/28)
Synthesis of deuterium-labeled CB1 receptor antagonist 2-d 9 was accomplished in three steps by alkylation of 2-nitrophenylacetonitrile with cyclopentyl-d9 bromide, reductive cyclization of the resulting secondary nitrile into the 3-cyclopentyl indole-d9 and its N-sulfonylation with corresponding p-amidosulfonyl chloride. Another, structurally related, CB1 receptor antagonist 1 was radiolabeled with carbon-14 by oxidative cleavage of 3-cyclopentyl indole followed by the ring closure of o-acyl substituted N-formylaniline with potassium cyanide-[14C], in situ reduction-elimination of the intermediate amino alcohol, and N-sulfonylation of the resulting 3-cyclopentyl indole-2-[14C]. Copyright
