WO2010019097 Pharmaceutical product comprising a muscarinic receptor antagonist and a second active ingredient

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Biological target:

Muscarinic acetylcholine receptor: M3

Activity:

Antagonist

Steps Conditions Reactions
a

CuI / 1,10-phenanthroline / Cs2CO3 / toluene

Ether synthesis (Ullmann reaction)
b NaH / DMF Thioether synthesis (Nucleophilic substitution)
Steps Conditions Reactions
a

CDI / NaBH4 / THF

Hydroxyl synthesis (Carboxylic acid reduction)
b Oxalyl chloride / DMSO / DCM Aldehyde synthesis (Swern reaction)
c NH2-OH, HCl / K2CO3 / H2O  Oxime synthesis
d TMS-trifluoromethanesulfonate / 2,6-lutidine / DCM TMS protection
e

tert-butylhypochlorite / propargyl chloride / Et3N / DCM

Cyclisation
f

TBAF / THF

TMS deprotection
Steps Conditions Reactions
a

NH2-NH2 / CDI / DCM

Hydrazine synthesis (CDI coupling)
b Chloroacetyl chloride / DIEA / DCM Acylation
c 1,2,2,6,6-pentamethylpiperidine / Tosylchloride / DCM  Cyclisation                  
d LiBr / acetone Bromination
Steps Conditions Reactions
a

THF

Grignard reaction
b NBS / AIBN / DCE Bromination
Steps Conditions Reactions
a

ACN

Quaternary amine synthesis (nucleophilic substitution)
Steps Conditions Reactions
a

ACN

Quaternary amine synthesis (nucleophilic substitution)