A facile nucleophilic displacement of bromine in 2-amino-4-methyl-5-bromothiazole by a thiophenoxide anion

Novel N-thiazolyl piperazine-1-carboxamide CCR2 antagonists – investigation of an unexpected reaction with glutathione

“…The effects of different 2-substituents on the reactivity of 5-halothiazoles towards displacement of the halogen by nucleophiles have been reported in the synthetic chemistry literature. In reaction with 4-chlorobenzenethiolate anion (in ethanol at reflux) 2-amino-4-methyl-5-bromothiazole was much more reactive than 2-acetamido-4-methyl-5bromothiazole 4, 9 which is consistent with our results since 4 showed no reaction with glutathione. Neutral chlorobenzenethiols also reacted with 2-amino-4-methyl-5bromothiazole under these conditions and the rate was reported to be slower.…”

“…[11][12][13][14] All calculations were performed in Gaussian09 and reported energies are free energies in kcal mol −1 and distances in figures are given in Ångströms. 15 The thiolate of glutathione was modelled as the anion of methane thiol; the slower rate of reaction with neutral thiols, mentioned above, 9 is assumed to be caused by the reduced concentration of the thiolate. Model compounds 6 were used in which the remote urea or amide were abbreviated to simplify the calculations.…”

Discovery of Novel and Potent Thiazoloquinazolines as Selective Aurora A and B Kinase Inhibitors

“…A mixture of 33 (12 g, 36 mmol), Cs 2 CO 3 (52 g, 164 mmol), and 1-bromo-2-chloroethane (5 mL, 60 mmol) in CH 3 CN (160 mL) was refluxed for 2 h. The reaction mixture was cooled, the solvent evaporated, and the residue was suspended in H 2 O (300 mL). This was extracted with CH 2 Cl 2 ( {2-[(7-{3-[(2S)-2-(Hydroxymethyl)pyrrolidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1,3-thiazol-5-yl}acetic Acid (50). A solution of 49 (1 g, 1.84 mmol) in DMA (7 mL) was reacted with (2S)-pyrrolidin-2-ylmethanol (908 µL, 9.2 mmol) at 90 °C for 3 h. The solvent was evaporated, and the crude reaction mixture was solubilized in EtOH and saponified with NaOH (6 N, 700 µL) at 80 °C for 3 h. The mixture was acidified with diluted HCl (2 N) to pH 3, evaporated, and dissolved in a mixture of MeOH:CH 2 Cl 2 (4:6).…”

Practical Synthesis of 2-Amino-5-fluorothiazole Hydrochloride

“…These routes included the Balz−Schiemann fluorodediazoniation of 2-acetamido-5-aminothiazole and the direct formation of the 2-amino-5-fluorothiazole ring system via the condensation of chlorofluoroacetaldehyde hydrate with thiourea by a process analogous to that employed previously for the synthesis of 2-amino-5-chlorothiazole . Nucleophilic aromatic substitution reactions of fluoride with 2-amino- or 2-acetamidothiazoles bearing a leaving group at the 5-position were also not useful.…”