Optimisation of a Key Cross-Coupling Reaction Towards the Synthesis of a Promising Antileishmanial Compound

TY - JOUR

T1 - Optimisation of a Key Cross-Coupling Reaction Towards the Synthesis of a Promising Antileishmanial Compound

AU - Velasco, Raul F.

AU - Guerrero, César

AU - Fra, Gloria

AU - Moure, Alejandra

AU - Miguel-Siles, Juan

AU - Quesada-Campos, Maria Teresa

AU - Ruiz-Gomez, Jose Ramon

AU - Gilbert, Ian H.

AU - Thomas, Michael G.

AU - Miles, Timothy J.

N1 - Funding: Wellcome Trust (92340; 100476)

PY - 2019/5/2

Y1 - 2019/5/2

N2 - During the course of a research program aimed at identifying novel antileishmanial compounds, a multi-gram synthesis of N-(trans-4-((4-methoxy-3-((R)-3-methylmorpholino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)cyclohexyl)-2-methylpropane-1-sulfonamide ((R)-1) was required. This letter describes optimisation of the reaction conditions and protecting group strategy for a key Buchwald-Hartwig coupling, delivering the required quantities of (R)-1, as well as further compounds in the series.

AB - During the course of a research program aimed at identifying novel antileishmanial compounds, a multi-gram synthesis of N-(trans-4-((4-methoxy-3-((R)-3-methylmorpholino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)cyclohexyl)-2-methylpropane-1-sulfonamide ((R)-1) was required. This letter describes optimisation of the reaction conditions and protecting group strategy for a key Buchwald-Hartwig coupling, delivering the required quantities of (R)-1, as well as further compounds in the series.

KW - 2-(Trimethylsilyl)ethoxymethyl (SEM)

KW - Buchwald-Hartwig coupling

KW - Protecting group strategy

KW - Visceral leishmaniasis

UR - https://www.scopus.com/pages/publications/85063743593

U2 - 10.1016/j.tetlet.2019.03.068

DO - 10.1016/j.tetlet.2019.03.068

M3 - Article

C2 - 31057189

SN - 0040-4039

VL - 60

SP - 1243

EP - 1247

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 18

ER -