15196-02-8Relevant articles and documents
α-Xanthylmethyl Ketones from α-Diazo ketones
López-Mendoza, Pedro,Miranda, Luis D.
, p. 3777 - 3790 (2021/07/07)
A simple and efficient method to obtain α-xanthylmethyl ketones from α-diazo ketones is described. The reaction proceeds through a protonation/nucleophilic substitution sequence in the presence of p -toluenesulfonic acid and potassium ethyl xanthogenate as the nucleophile. As α-diazo ketones can be readily synthesized from ubiquitous carboxylic acids, a broad variety of xanthates can be obtained, including examples from naturally occurring substrates.
SUBSTITUTED AZETIDINE DERIVATIVES AS TAAR LIGANDS
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Page/Page column 96, (2016/03/22)
The present invention relates to a compound of formula I wherein R1 is hydrogen, methoxy or fluoro; R2/R2' are independently from each other hydrogen, methoxy or fluoro; R3/R4 are independently from each other hydrogen or halogen; R is hydrogen or fluoro; L1 is -CH2-, -NR'-, -0-, -S-, CF2- or CH=; R' is hydrogen or lower alkyl; L2 is a bond, -C(0)NH-, -NH-, -CH2NHC(O)-, -NHC(O)- or -NHC(0)NH-; R is hydrogen, halogen, lower alkoxy, cyano or is phenyl optionally substituted by one or more substituents, selected from halogen, lower alkyl substituted by halogen or lower alkoxy, or is a five or six membered heteroaryl, selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl or pyrazolyl, which heteroaryls are optionally substituted by one or more substituents, selected from halogen, lower alkyl, lower alkoxy, cyano, cycloalkyl, lower alkyl substituted by halogen, lower alkoxy substituted by halogen or by phenyl substituted by halogen; N is a ring nitrogen atom in position 1 or 2; or to a pharmaceutically suitable acid addition salt thereof. The compounds of formulas I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1 and may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
Continuous flow synthesis of α-halo ketones: Essential building blocks of antiretroviral agents
Pinho, Vagner D.,Gutmann, Bernhard,Miranda, Leandro S. M.,De Souza, Rodrigo O. M. A.,Kappe, C. Oliver
, p. 1555 - 1562 (2014/03/21)
The development of a continuous flow process for the multistep synthesis of α-halo ketones starting from N-protected amino acids is described. The obtained α-halo ketones are chiral building blocks for the synthesis of HIV protease inhibitors, such as atazanavir and darunavir. The synthesis starts with the formation of a mixed anhydride in a first tubular reactor. The anhydride is subsequently combined with anhydrous diazomethane in a tube-in-tube reactor. The tube-in-tube reactor consists of an inner tube, made from a gas-permeable, hydrophobic material, enclosed in a thick-walled, impermeable outer tube. Diazomethane is generated in the inner tube in an aqueous medium, and anhydrous diazomethane subsequently diffuses through the permeable membrane into the outer chamber. The α-diazo ketone is produced from the mixed anhydride and diazomethane in the outer chamber, and the resulting diazo ketone is finally converted to the halo ketone with anhydrous ethereal hydrogen halide. This method eliminates the need to store, transport, or handle diazomethane and produces α-halo ketone building blocks in a multistep system without racemization in excellent yields. A fully continuous process allowed the synthesis of 1.84 g of α-chloro ketone from the respective N-protected amino acid within ～4.5 h (87% yield).
