WO2010040663 Pyrrolidine N-Benzyl derivatives

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Scaffold: pyrrolidine

Biological target:

Neurokinin: NK3

Activity:

Inhibitor

Steps Conditions Reactions
a DCM / TFA Cyclisation
b SnCl2 / EtOAc 
Primary amine synthesis (nitro reduction)
c

1. Ethylchloroformate / K2CO3 / THF / H2O 

2. Borane / THF

N-Methylation synthesis
d NaBH3CN / MeOH / AcOH  Tertiary amine synthesis (reductive amination) 
e

1. 2,2,2-trichloroethyl chloroformate / ACN 

2. Zn / AcOH

Benzyl deprotection

 


Steps Conditions Reactions
a DCM / TFA
Cyclisation
b TiCl4 / Zn / THF 
Primary amine synthesis (nitro reduction)
c

1. Ethyl chloroformate / K2CO3 / THF / H2O 

2. Borane / THF 

N-Methylation synthesis
d Boc2O / Et3N / DMAP / DCM  Boc protection 
e 1-chloroethyl chloroformate / toluene  Benzyl deprotection 
f

1. EDCI / HOBt / Et3N / DCM

2. TFA / DCM

Amide synthesis (EDCI coupling) / Boc deprotection
g NaBH3CN / MeOH / AcOH Tertiary amine synthesis (reductive amination)

 


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