WO2010010184 [1,2,4]triazolo[1,5-A]pyridines as JAK inhibitors

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Scaffold: Triazolopyridine

Biological target:

Janus kinase: JAK

Activity:

Inhibitor

Steps	Conditions	Reactions
a	DCM	Thiourea synthesis
b	NH₂-OH / DIEA / EtOH:MeOH (1:1)	Cyclisation
c	PdCl₂dppf / K₂CO₃ / dioxane:H₂O (5:1)	Suzuki reaction
d	Pd(AcO)₂ / BINAP / Cs₂CO₃ / dioxane	Buchwald -Hartwig amination
e	1. SnCl₂ / EtOH 2. Ac₂O / THF	Primary amine synthesis (nitro reduction) / Acylation

Steps	Conditions	Reactions
a	PdCl₂dppf / K₂CO₃ / dioxane:H₂O (5:1)	Suzuki reaction
b	Pd(AcO)₂ / BINAP / Cs₂CO₃ / dioxane	Buchwald-Hartwig amination
c	1. LiOH / Acetone 2.CH₃-NH₂ / EDCI / HOBt / Et₃N / DMF	Carboxylic acid synthesis (Ester hydrolysis) / Amide synthesis (EDCI coupling)

Steps	Conditions	Reactions
a	TMS-diazomethane / THF	Ester synthesis (Esterification)
b	MeMgBr / THF	Grignard reaction
c	Bis(pinacolato)diboron / Pd(dppf)Cl₂ / AcOK / dioxane	Boronic ester synthesis

Steps	Conditions	Reactions
a	CSCl₂ / DCM	Thioisocyanide synthesis
b	THF	Thiourea synthesis
c	1. CH₃I / NaH / THF 2. NH₂OH.HCl / DIEA / EtOH	S-Methylation / Imine synthesis
d	TFA / THF	Cyclisation

Steps	Conditions	Reactions
a	NaH / NMP	Nucleophilic susbtitution
b	Bis(pinacolato)diboron / Pd(dppf)Cl₂ / AcOK / dioxane	Boronic ester synthesis

Steps	Conditions	Reactions
a	Titanium tetraisoproxide / (R)-t-butyl sulfinamide / THF	Imine substitution
b	MeMgBr / DCM	Grignard reaction
c	HCl 4N / dioxane / MeOH	Primary amine synthesis
d	2-chloroethyl ether / K₂CO₃ / DMF	Morpholine synthesis (nucleophilic substitution)
e	Bis(pinacolato)diboron / Pd(dppf)Cl₂ / AcOK / dioxane	Boronic ester synthesis

Steps	Conditions	Reactions
a	1. Ti(Oi-Pr)₄ / EtMgBr / Et₂O 2. BF₃.Et₂O	Cyclopropyl synthesis
b	1-bromo-2-(2-bromo-ethoxy)-ethane / DIPEA / DMF	Morpholine synthesis (nucleophilic substitution)
c	Bis(pinacolato)diboron / Pd(dppf)Cl₂ / AcOK / dioxane	Boronic ester synthesis

Steps	Conditions	Reactions
a	1. Ti(Oi-Pr)₄ / EtMgBr / Et₂O 2. BF₃.Et₂O	Cyclopropyl synthesis
b	Divinyl sulfone / Na₂CO₃ / isopropanol / H₂O	Nucleophilic substitution
c	Bis(pinacolato)diboron / Pd(dppf)Cl₂ / AcOK / Dioxane	Boronic ester synthesis

Steps	Conditions	Reactions
a	CHCl₃ / NaOH / Acetone
b	1. SOCl_2. _{2.NH₃ aq}	Primary amide synthesis
c	Bis(pinacolato)diboron / Pd(dppf)Cl₂ / AcOK / dioxane	Boronic ester synthesis

Steps	Conditions	Reactions
a	1. MeLi / CeCl₃ / THF 2. Boc₂O
b	1-bromo-2-(2-bromo-ethoxy)-ethane / DIPEA / DMF	Morpholine synthesis (nucleophilic substitution)
c	Bis(pinacolato)diboron / Pd(dppf)Cl₂ / AcOK / Dioxane	Boronic ester synthesis

Steps	Conditions	Reactions
a	DBU / DMF	Nucleophilic substitution