Syntheses of two isotopically labeled CB1 receptor antagonists

Synthesis of deuterium-labeled CB1 receptor antagonist 2-d9 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].