WO2010061329 3-aminocyclopentanecarboxamides as chemokine receptor modulators

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Scaffold:3-aminocyclopentanecarboxamide

Biological target:

Chemokine receptors: CCR2, CCR5

Activity:

Inhibitor

Steps Conditions Reactions
a Ethyl iodide / LDA / THF  Nucleophilic substitution
b NaOH 2.5N / MeOH Carboxylic acid synthesis (ester hydrolysis)
c (1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptane / BOP / DIEA / DMF Amide synthesis (BOP coupling)
d Hydroxylamine / H2O / MeOH Amine deprotection (pyrrole group)
e H2 / Pd-C / MeOH Alkene reduction
f Sodium acetoxyborohydride / DCM Primary amine synthesis (Amination reductive)
g HCl 4N / Dioxane Boc deprotection
h DMSO Tertiary amine synthesis (Nucleophilic substitution)
Steps Conditions Reactions
a

1. NaOH 2.5N / MeOH

2.BnOH / EDCI / DMAP / DCM

Hydrolysis / Ester synthesis
b LDA / THF
Nucleophilic substitution
c Hydroxylamine / MeOH
Amine deprotection (Pyrrole deprotection)
d Sodium triacetoxyborohydride / DCM
Secondary amine synthesis (Amination reductive)
e trifluoroacetic anhydride / DIEA / DCM COCF3 protection
f Acetyl chloride / DIEA / DMAP / DCM Acetyl synthesis
g H2 / Pt-C / Pd-C / AcOH Alkene reduction / O-Benzyl deprotection
h

1. Oxalyl chloride / DCM

2. DIEA / DCM

Amide synthesis 
i

1.K2CO3 / MeOH

2.NaBH4 / EtOH

3. HCl 4N / Dioxane

Acetyl deprotection / COCF3 deprotection / Boc deprotection 
Steps Conditions Reactions
a DAST / DCM Fluorination

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