WO2010006191 4-phenoxymethylpiperidines as modulators of GPR119 activity

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Biological target:

G protein-coupled receptor 119: GPR119

Activity:

Modulator

Steps	Conditions	Reactions
a	K₂CO₃ / DMA	Tertiary amine synthesis (Nucleophilic substitution)
b	MsCl / Et₃N / DCM	Mesyl synthesis
c	Cs₂CO₃ / DMF	Ether synthesis
d	Bis(pinacolato)diboron / Pd(dppf)Cl₂ / AcOK / DMSO	Ester boronic synthesis
e	Pd(dppf)Cl₂ / Cs₂CO₃ / dioxane	Suzuki reaction

Steps	Conditions	Reactions
a	TsCl / Pyridine	Tosyl synthesis
b	Cs₂CO₃ / DMF	Thioether synthesis
c	m-CPBA / DCM	Oxidation
d	bis(pinacolato)diboron / Pd(dppf)Cl₂ / AcOK / DMSO	Ester boronic synthesis

Steps	Conditions	Reactions
a	Toluene
b	EtMgBr / Et₂O	Cyclopropyl synthesis
c	4-nitrophenyl chloroformate / DMAP / 2,4,6-collidine / DCM	Carbamate synthesis
d	1. TFA / DCM 2. Et₃N / DCM	Boc deprotection / Nuclephilic substitution

Steps	Conditions	Reactions
a	Sodium methanesulfinate / [Cu(I)OTf]₂Ph / Dimethylethyldiamine / Cs₂CO₃ / DMSO

Steps	Conditions	Reactions
a	NaI / AcCl / ACN	Iodination
b	1H-1,2,4-triazole / [Cu(I)OTf]₂Ph / Dimethylethyldiamine / Cs₂CO₃ / DMSO

Steps	Conditions	Reactions
a	m-CPBA / AcOEt	N-oxide pyridine synthesis
b	Ac₂O
c	MeI / Cs₂CO₃ / DMF	N-Methylation

Steps	Conditions	Reactions
a	Pd(OAc)2 / Ph₂P(CH₂)₃PPh₂ / CO / Et₃N / DMA:MeOH (1:1)	Ester synthesis

Steps	Conditions	Reactions
a	Pd(dppf)Cl₂ / Cs₂CO₃ / dioxane	Suzuki reaction
b	K₂CO₃ / MeOH

Steps

Conditions

Reactions

a

1. ACN

2. NaOH