WO2010018112 Monoaryl aminotetralines

WO2010018112.pdf
Adobe Acrobat Document 3.7 MB

Scaffold: aminotetraline

Biological target:

Prostaglandin D2 receptors: CRTH2

Activity:

Antagonist

Steps Conditions Reactions
a H2 / NaOHaq / Pd(OH)2 / Isopropanol Aromatic reduction
b Cs2CO3 / ACN Ether synthesis (nucleophilic substitution)
c

1. Ammonium acetate / NaBH3CN / MeOH

2. Chiral separation

Primary amine synthesis (reductive amination)
Steps Conditions Reactions
a DIEA / THF Sulfonamide synthesis (coupling reaction)
b CH3-I / K2CO3 / DMF N-methylation
c NaOH 2N / THF Tert-butyl deprotection
Steps Conditions Reactions
a Propane-2-thiol / K2CO3 / DMF Thioether synthesis (aromatic substitution)
b m-CPBA / DCM Oxidation
c NaOH 2M / THF tert-butyl deprotection
Steps Conditions Reactions
a  Pyrrolidine / DMSO Tertiary amine synthesis (aromatic substitution)
Steps Conditions Reactions
a PPh3 / DIAD / 2-methyl-tetrahydrofuran Tertiary amine synthesis (Mitsunobu reaction)
Steps Conditions Reactions
a [RuCl2(C10H14)]2 / (1S,2S)-(+)-N-p-tosyl-1,2-diphenylethylenediamine / Formic acid : Et3N (5:2) Hydroxyl chiral synthesis (ketone chiral reduction)
b DPPA / DBU / toluene Azido synthesis
c H2 / Pd-C / MeOH Primary amine synthesis (Azido reduction)
Steps Conditions Reactions
a Pd(PPh3)4 / tBuOK / DMF
Suzuki reaction
b LiOH 1M / THF tert-butyl deprotection
c SOCl2 / MeOH Ester synthesis (Esterification)
d CH3-I / K2CO3 / DMF N-methylation
e

1. NaOH 40% / Et2O

2. Pd(AcO)2

Cyclopropyl synthesis 
Steps Conditions Reactions
a H2 / Pd-C / AcOEt Alkene reduction
Steps Conditions Reactions
a BnBr / K2CO3 / ACN N-Benzyl protection
b Tris(dibenzylideneacetone)dipalladium(0) / triphenylarsine / DMF Stille coupling
c Bis(2-methoxyethyl)aminosulfur trifluoride / DCM Fluorination
d Formic acid ammonium salt / Pd-C / EtOH N-Benzyl deprotection

Site Search