ETHYL2-CHLOROTHIAZOLE-5-CARBOXYLATE

At 23°C, a solution of ethyl 2-aminothiazole-4-formate (1.0 g, 6.35 mmol) in acetonitrile (10 mL) and tetrahydrofuran(10 mL) is added to a solution (10 mL) of t-butyl nitrite (1.3 mL, 9.52 mmol) and cuprous chloride (1.0 g, 7.6mmol) in acetonitrile (10 mL) and tetrahydrofuran (10 mL). The reaction mixture is required to be heated at 65 °C untilcomplete consumption of the starting materials as shown by thin-layer chromatography (40percent ethyl acetate-hexane).Then, the mixture is cooled to room temperature and partitioned between water and ethyl acetate. The organic layer isconcentrated under vacuum and purified by flash silica gel column chromatography eluted with 20percent ethyl acetate-hexaneto give ethyl 2-chloro-thiazole-4-formate (compound (2-2)) (0.49 g, 40percent).Example 27A Example 1262-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-thiazole-5-carboxylic acid ethyl esterTo a stirred suspension of sodium hydride (304 mg, 6.98 mmol, 60% dispersion in mineral oil) in tetrahydrofuran (30 mL) at 00C under argon was added (5 -methyl-3 -phenyl- isoxazo 1-4- yl)-methanol (1.0 g, 5.28 mmol) The mixture was warmed to roomtemperature and after 1 h the reaction mixture was cooled to 00C then a solution of Example 1322-(3-Butyl-5-methyl-isoxazol-4-ylmethoxy)-thiazole-5-carboxylic acid isopropylamidea) 2-Chloro-thiazole-5-carboxylic acid isopropylamideTo a stirred solution of isopropylamine (123 mg, 2.08 mmol) in dioxane (5 mL) under argon and at room temperature was added trimethylaluminium (1.04 mL of a 2M solution in toluene, 2.08 mmol). After 1 h, a solution of 1, 1 -Dimethyl ethyl 1 -piperazinecarboxylate (1.86 g, 10 mmol), methyl 2-chloro-5- thiazolecarboxylate (1.92 g, 10.0 mmol), diazabicycloundecene (1.5 mL, 10 mmol) and a catalytic amount of potassium iodide (2 mg) were dissolved in 10 mL of dry dimethyl sulfoxide and warmed to 80 0C for 16 h. The warm solution was added dropwise with stirring to 200 mL of cold water. The reaction mixture was extracted with diethyl ether. The resulting extract was washed with water and brine, dried over magnesium sulfate and concentrated under reduced pressure to give 3.23 g of a yellow oil which solidified on standing. The solid was recrystallized from diethyl ether/hexanes to give 1.0 g of the title compound as light yellow crystals. This compound was of sufficient purity to use in subsequent reactions.1H NMR (CDCl3) delta 1.37 (t, 3H), 1.48 (s, 9H), 3.53 (s, 8H), 4.38 (q, 2H), 7.47 (s, IH).

Molecular Weight:191.64
XLogP3:2.5
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:190.9807773
Monoisotopic Mass:190.9807773
Topological Polar Surface Area:67.4
Heavy Atom Count:11
Complexity:156
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes