2,4-DIBROMO-THIAZOLE-5-CARBALDEHYDE,97%

Brown powder

Preparation of Intermediates for Example 26 and Related Analogs 2, 4-Dibromo-thiazole-5-carbaldehyde A mixture of thiazolidine-2, 4-dione (15.0 g, 128 mmol), POBr3 (183.6 g, 640 mmol) andDMF(i0.8 ml, 140.9 mmol) was heated to 75 °C for 1 h and then at 100 °C for 5 h. Thereaction mixture was cooled to room temperature, diluted with CH2C12 and washed with saturated NaHCO3 solution, filtered and concentrated. Trituration of the evaporation residue with petroleum ether afforded 8.0 g of 2, 4-dibromothiazole-5 -carbaldehyde 8.0 g as black solid.Step 1: 2, 4-Dibromothiazole-5-carbaldehyde (25a)To a solution of LDA (1M in THE, 183 mL, 183 mmol) was added a solution of 2, 4- dibromothiazole (37 g, 154 mmol) in dry THF (500 mL) at —78°C under N2 and the solution was stirred under this condition for 40 mm. Then DMF (13 g, 178 mmol) was added slowly at this temperature and the solution was stirred for another 1 h, warmed to rt, quenched with sat.NH4CI and extracted with EA twice. The combined organic layers were washed with water and brine, dried over Na2SO4, filtered, concentrated and purified by CC (PE/EA = 15/1) to give compound 25a (14.5 g, 35percent) as a yellow solid.2, 4-Dibromo-thiazole-5-carbaldehyde (2.0 g, 7.4 mmol) in methanol (80 mL) was treated with NaBH4 (419 mg, 11.0 mmol). The reaction mixture was stirred at rt overnight, quenched with 10% NaOH, diluted with water and extracted with ethyl acetate (2X). The solvent was removed, and the resulting residue was chromatographed using hexane/ethyl acetate (3:1) to give the title compound (1.84 g, 91 %). MS (DCI/NH3) m/z 274 (M)+. 'HNMR(500 MHz, CDC13) ppm 2.11 (s, 1 H) 4.78 (s, 2 H).b) (2, 4-Dibromo-1, 3-thiazol-5-yl)methanol. 2, 4-Dibromo-1, 3-thiazole-5-carbaldehyde (1.74 g, 6.42 mmol) was dissolved in methanol (70 ml) at 0 C. Sodium borohydride (0.244 g, 6.42 mmol) was added in small portions. The ice-water bath was removed 10 minutes later and the reaction mixture was stirred at room temperature overnight. Solvent was removed and saturated ammonium chloride was added. 1.0N NaOH was added to adjust the pH to 10. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatogrphy to give (2, 4-dibromo-1, 3-thiazol-5-yl)methanol (0.946 g, 3.47 mmol). 1H NMR (CDCl3-d) delta2.11 (bs, 1H) delta4.79 (S, 2H).b (2, 4-Dibromo-1, 3-thiazol-5-yl)methanol 2, 4-Dibromo-1, 3-thiazole-5-carbaldehyde (1.74 g, 6.42 mmol) was dissolved in methanol (70 ml) at 0 C. Sodium borohydride (0.244 g, 6.42 mmol) was added in small portions. The ice-water bath was removed 10 minutes later and the reaction mixture was stirred at room temperature overnight. Solvent was removed and saturated ammonium chloride was added. 1.0N NaOH was added to adjust the pH to 10. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatogrphy to give (2, 4-dibromo-1, 3-thiazol-5-yl)methanol (0.946 g, 3.47 mmol). 1H NMR (CDCl3-d) delta2.11 (bs, 1H), 4.79 (S, 2H).To a solution of Preparation of Intermediates for Example 26 and Related Analogs 2, 4-Dibromo-thiazole-5-carbaldehyde To a mixture of 2, 4-thiazolidinedione (technical grade, 90%; 19.1 g, 147 mmol) and POBr3 (210 g, 734 mmol) at 0 C. was added dropwise dimethylformamide (12.5 ml, 161.5 mmol). The resulting solid was heated to 105 C. for 8 hrs. The dark oil solidified upon cooling. A large amount of ice was added to quench the excess POBr3. The precipitate was filtered and the filtrate was extracted with 3*200 ml CH2Cl2. The combined organics were washed with 50 ml saturated NaHCO3 and 100 ml brine, dried with MgSO4 and concentrated in vacuo to afford a brown solid. The crude was purified by flash chromatography with 0 to 5% ethyl acetate/Hexanes to afford A mixture of thiazolidine-2, 4-dione (15.0 g, 128 mmol), POBr3 (183.6 g, 640 mmol) andDMF(i0.8 ml, 140.9 mmol) was heated to 75 C for 1 h and then at 100 C for 5 h. Thereaction mixture was cooled to room temperature, diluted with CH2C12 and washed with saturated NaHCO3 solution, filtered and concentrated. Trituration of the evaporation residue with petroleum ether afforded 8.0 g of 2, 4-dibromothiazole-5 -carbaldehyde 8.0 g as black solid.Step 2: Cyclohexyl(2, 4-dibromothiazol-5-yl)methanol (25b) To a solution of compound 25a (11.2 g, 41.7 mmol) in dry THE (150 mL) was added a solution of cyclohexylmagnesium chloride (1 M in THE, 45 mL, 45.0 mol) at -78C and the solution was stirred at this temperature for 1 h, warmed to rt, quenched with water and extracted with EA twice. The cominbed organic layers were washed with water and brine, dried over Na2SO4, filtered, concentrated and purified by CC (PE/EA = 20/1) to give compound 25b (5.4 g, 37%)a pale yellow solid.Step 1: 2, 4-Dibromothiazole-5-carbaldehyde (25a)To a solution of LDA (1M in THE, 183 mL, 183 mmol) was added a solution of 2, 4- dibromothiazole (37 g, 154 mmol) in dry THF (500 mL) at -78C under N2 and the solution was stirred under this condition for 40 mm. Then DMF (13 g, 178 mmol) was added slowly at this temperature and the solution was stirred for another 1 h, warmed to rt, quenched with sat.NH4CI and extracted with EA twice. The combined organic layers were washed with water and brine, dried over Na2SO4, filtered, concentrated and purified by CC (PE/EA = 15/1) to give compound 25a (14.5 g, 35%) as a yellow solid.2, 4-Dibromo-thiazole-5-carboxylic acid Solid potassium permanganate (2.19 g, 13.85 mmol) was added portionwise to a hot suspension of a) 2, 4-Dibromo-1, 3-thiazole-5-carbaldehyde. 1, 3-Thiazolane-2, 4-dione (3.52 g, 30 mmol) and phosphorus oxybromide (43 g, 150 mmol) were mixed with dimethyl formamide (2.56 mL, 34 mmol). The mixture was then heated at 75 C. for 1 hours and at 100 C. for 5 hours. After cooled to room temperature, the mixture was added to ice-water (500 ml) and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with saturated sodium bicarbonate, dried over MgSO4, filtered and evaporated to give a brown solid which was washed with petroleum ether. Evaporation of solvent gave

Molecular Weight:270.93
XLogP3:2.8
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:270.81251
Monoisotopic Mass:268.81456
Topological Polar Surface Area:58.2
Heavy Atom Count:9
Complexity:123
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes