No abstract

Melanin-concentrating hormone (MCH) is implicated in the feeding behavior in mammals affording a potential target to control overeating in people. Compound 1 (AMG 076) has been identified as a potent MCHr1 antagonist for the treatment of obesity. A synthesis suitable for the large-scale preparation of this lead candidate was developed to support preclinical studies. A Robinson annulation of benzylpiperidone and resolution of the desired enone from a mixture of the diastereomers afforded key intermediate 6 after a stereoselective hydrogenation. Subsequent Fischer indole synthesis with hydrazine 5 then provided the advanced intermediate, indole 2. Two complementary reductive amination strategies employing either aldehyde 3 or lactol 4 led to the synthesis of title compound 1.

No abstract

SUMMARY@-(I ,3-Dithianyl))myrtanylborane (MDBHd, a stable asymmetric monoalkylborane, was converted into deuterated or tritiated analogues used to prepare enantiomeric labelled alcoholsfrom 1-phenylcyclopemene with a high isotopic enrichmem (%95% for deuterium; 8b8996 for tritium) and a high asymmetric induction (80% ee for deuterium; 75% ee for tritium).

SUMMARYTritiated methylborane prepared from tritium gas and methaneboronic acid was used to prepare [2-H3]-trans-2-phenylcyclopentylamine from I -phenylcyclopcnrenu with a high specijk activity (26Ci/mmol) in 20-40% yield.