63416-84-2

Upstream product

• 594-39-8 2-methyl-2-butylamine 
• 352-34-1 4-fluoro-1-iodobenzene 
• 352-11-4 1-chloromethyl-4-fluorobenzene 
• 88023-07-8 ethyl 2-<(4-fluorophenyl)methyl>-3-oxobutanoate 
• 63416-61-5 4-(4-fluorophenyl)-2-butanone 
• 63416-82-0 3-(4-fluorophenyl)-1,1-dimethylpropanol 
• 143627-96-7 N-[3-(4-Fluoro-phenyl)-1,1-dimethyl-propyl]-formamide 

Downstream Products

• 143627-93-4 N-<3-(4-fluorophenyl)-1,1-dimethylpropyl>thiourea 
• 63416-83-1 α1-[[[3-(4-Fluorophenyl)-1,1-dimethylpropyl]amino]methyl]-4-(phenylmethoxy)-1,3-benzenedimethanol 
• 143627-92-3 1-Benzoyl-3-[3-(4-fluoro-phenyl)-1,1-dimethyl-propyl]-thiourea 

Relevant academic research and scientific papers

Native amine-directed site-selective C(sp3)-H arylation of primary aliphatic amines with aryl iodides

Direct C(sp3)-H functionalization of N-unprotected aliphatic amines represents one of the most efficient and straightforward strategies for amine synthesis. Despite some recent progress in this field, the NH2-directed γ-C(sp3)-H arylation of primary aliphatic amines except α-amino esters remained an unmet challenge. In this report, we established a simple and efficient method for site-selective C(sp3)-H arylation of primary aliphatic amines by aryl iodides. In the presence of only 5 mol% Pd(OAc)2, a wide range of aliphatic amines including O-benzyl and O-silyl amino alcohols were arylated at γ- or δ-positions by aryl iodides containing a broad scope of functional groups. The synthetic application of this method had also been demonstrated by large-scale synthesis, the synthesis of a fingolimod analogue, and the conjugation with natural D-menthol and fluorescent 1,8-naphthalimide.

Carbon Dioxide as a Directing Group for C-H Functionalization Reactions Involving Lewis Basic Amines, Alcohols, Thiols, and Phosphines for the Synthesis of Compounds

Methods of synthesizing compounds using CO2 as a directing group for C—H functionalization, and compounds made thereby, are described.

Carbon Dioxide-Mediated C(sp3)-H Arylation of Amine Substrates

Elaborating amines via C-H functionalization has been an important area of research over the past decade but has generally relied on an added directing group or sterically hindered amine approach. Since free-amine-directed C(sp3)-H activation is still primarily limited to cyclization reactions and to improve the sustainability and reaction scope of amine-based C-H activation, we present a strategy using CO2 in the form of dry ice that facilitates intermolecular C-H arylation. This methodology has been used to enable an operationally simple procedure whereby 1° and 2° aliphatic amines can be arylated selectively at their γ-C-H positions. In addition to potentially serving as a directing group, CO2 has also been demonstrated to curtail the oxidation of sensitive amine substrates.

Palladium-Catalyzed C(sp3)?H Arylation of Primary Amines Using a Catalytic Alkyl Acetal to Form a Transient Directing Group

C?H Functionalization of amines is a prominent challenge due to the strong complexation of amines to transition metal catalysts, and therefore typically requires derivatization at nitrogen with a directing group. Transient directing groups (TDGs) permit C?H functionalization in a single operation, without needing these additional steps for directing group installation and removal. Here we report a palladium catalyzed γ-C?H arylation of amines using catalytic amounts of alkyl acetals as transient activators (e.g. commercially available (2,2-dimethoxyethoxy)benzene). This simple additive enables arylation of amines with a wide range of aryl iodides. Key structural features of the novel TDG are examined, demonstrating an important role for the masked carbonyl and ether functionalities. Detailed kinetic (RPKA) and mechanistic investigations determine the order in all reagents, and identify cyclopalladation as the turnover limiting step. Finally, the discovery of an unprecedented off-cycle free-amine directed ?-cyclopalladation of the arylation product is reported.

Site-selective C-H arylation of primary aliphatic amines enabled by a catalytic transient directing group

Transition-metal-catalysed direct C-H bond functionalization of aliphatic amines is of great importance in organic and medicinal chemistry research. Several methods have been developed for the direct sp 3 C-H functionalization of secondary and tertiary aliphatic amines, but site-selective functionalization of primary aliphatic amines in remote positions remains a challenge. Here, we report the direct, highly site-selective γ-arylation of primary alkylamines via a palladium-catalysed C-H bond functionalization process on unactivated sp 3 carbons. Using glyoxylic acid as an inexpensive, catalytic and transient directing group, a wide array of γ-arylated primary alkylamines were prepared without any protection or deprotection steps. This approach provides straightforward access to important structural motifs in organic and medicinal chemistry without the need for pre-functionalized substrates or stoichiometric directing groups and is demonstrated here in the synthesis of analogues of the immunomodulatory drug fingolimod directly from commercially available 2-amino-2-propylpropane-1,3-diol.

Synthesis and histamine H2-agonistic activity of ring-substituted phenyl analogues of impromidine

Analogues of the H2-agonist impromidine, characterized by a substituted phenyl ring instead of the 5-methyl-4-imidazolyl group, were prepared and tested for their H2-agonistic and H1-antagonistic activity at the guinea-pig