WO2010015972 Diazepine and diazocane compounds as MC4 agonists

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Scaffold: Diazepine; Diazocane

Biological target:

G-protein coupled receptors of the melanocortin receptor family: MC4

Activity:

Agonist

Steps Conditions Reactions
a AlCl3 Ketone synthesis (Friedel-Crafts reaction)
b

 1. 4-methyl-penta-2-one / Dean-Stark

 2. Et3N / propan-2-ol / H2O

 3. NaBH4

Cyclisation
c Pd(OH)2 / ammanium formate / EtOH N-Benzyl deprotection
Steps Conditions Reactions
a Xylene / Dean-stark Cyclisation
b

LAH / Et2O

Opening reaction
Steps Conditions Reactions
a Oxalyl chloride / DCM / DMF Amide synthesis
b TFA / DCM Cyclisation
c Sm(CF3SO3)3 / MeOH Deprotection
d Pd(OH)2 / 1-methyl-1,4-cyclohexadiene / MeOH N-Benzyl deprotection
Steps Conditions Reactions
a (9,9-dimethyl-9H-xanthene-4,5-diyl)-bis[diphenyl phosphine] / Pd(OAc)2 / Toluene Buchwald-Hartwig amination
b NaOH 1N / 1,4-dioxane

Carboxylic acid synthesis (Ester hydrolysis)

c EDCI / HOBt / DIEA / DCM Amide synthesis (EDCI coupling)