3029-48-9

An efficient scalable synthesis of 2-halothiazolium-type peptide coupling reagents has been developed. The key step is the formation of the 2-bromothiazole scaffold through cyclization of α-thiocyanato ketones with hydrogen bromide. Using this method, the new coupling reagent 2-bromo-N-methylthiazolium bromide (BMTB) was synthesized. BMTB was tested in a difficult model coupling reaction of two sterically hindered N-methylated amino acids and showed higher activity than the well-established peptide coupling reagent HATU.

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A facile method is disclosed for the synthesis of α-thio/selenocyanato ketones through regioselective C-H thio/selenocyanation of ketones. The advantages include the use of easily available starting materials, high efficiency, simple operation, and easy scale-up. Control experiments provide evidence that the reaction proceeded via a radical way, while kinetic isotope effect experiments reveal that the cleavage of the C-H bond serves as the rate-limiting step.

Disclosed in the present invention are a new thiazole compound, particularly a compound represented by formula (I), a pharmaceutical composition thereof and applications thereof in the preparation of drugs for the treatment of diseases related to herpes simplex viruses.

An azo dye including a compound represented by formula (I): wherein R1 represents a hydroxyl group, an aliphatic sulfonyl amino group, an aryl sulfonyl amino group, an aliphatic oxy group, an aryloxy group, or -CH(R2)(R3); R2 and R3 each represent a substituent with a a value of the Hammett's rule in the range of 0.2 or more and less than 1.4, and may be identical to or different from each other; W represents a sulfur atom or -N-(-R4)-; R4 represents a substituent; R5 represents a substituent; X, Y, and Z each represent an atom required for forming a five-membered aromatic heterocycle, where at least one atom of X, Y, and Z represents a nitrogen atom but both X and Y do not represent a carbon atom when Z represents a nitrogen atom; and R6 represents a hydrogen atom or a substituent, n represents 1 or 2, and two R6s may be coupled together to form an aromatic ring or a heteroaromatic ring when n represents 2.

The present invention relates to compounds of formula (I): wherein R1 to R3, A, M, L, E, G, and J are as defined in the description and claims. The invention also relates to a process for the manufacture of such compounds, pharmaceutical compositions containing them, and methods for treating CNS disorders.

(Matrix presented) This paper describes Sonogashira cross-coupling of functionalized 2-, 4-, and 5-trifloyl oxazoles and thiazoles with terminal alkynes. This methodology has been extended to 2,4-ditrifloylthiazoles, which results in regioselective cross-coupling at the C2-position of the thiazole. The resulting 2-alkynyl-4-trifloylthiazoles are effective electrophiles in a second palladium(0)-mediated cross-coupling reaction.

The reaction of α-halo ketones 1 with potassium thiocyanate and amines 3 offers the advantage of an efficient one-pot synthesis of the title compounds 4 from readily available starting materials.