4-(3-Pyridinyl)-2-thiazolamine

A method of driving visible light to synthesize 4-alkyl or aryl-2-aminothiazoles. This method refers to adding olefin azide compound, ammonium thiocyanate and copper acetate to solvent acetonitrile, respectively, driving at a temperature of 25° C. under visible light with a wavelength of 455 nm, and obtaining a reaction solution after 28 h. The reaction solution was spin-dried at a temperature of 25° C. and a pressure of 1.3 kPa to obtain a concentrate; the concentrate was subjected to silica gel column chromatography (200 to 300 mesh silica gel, eluent: petroleum ether: ethyl acetate=1 mL: (1 mL) gives 4-(3-pyridyl)-2-aminothiazole (2m) as a white solid (14.6, 83percent).[00222j Step 2: Synthesis of 4-(pyridin-3-yl)thiazol-2-amine: To a solution of 2-bromo-1-(pyridin-3-yl)ethanone (2 g, 1 equiv.) in ethanol (18.46 mL), thiourea (0.543 g, 0.7 equiv.) was added. The reaction mixture was heated to reflux for 2 h. After completion of 2 h, the reaction mixture was cooled to 4 °C. On cooling the product precipitated out in dihydrobromide salt form. The material obtained was filtered and dried. 4-(pyridin-3-yl)thiazol-2-amine dihydrobromide salt was dissolved in warm water(11 mL) and stirred for 5 mm, to this aqueous ammonium hydroxide solution (17 mL) was added and stirred. The desired product slowly precipitated (yellow solid) which was filtered and dried under vacuum to afford 4-(pyridin-3-yl)thiazol-2-amine 2 g, 56percent yield). LCMS m/z 178.01 (M+H); ‘H NMR 400 MHz, CD3OD: ö 8.96 (d, J 0.80 Hz, 1H), 8.44 (dd, J= 1.60, 4.80 Hz, 1H), 8.19-8.22 (m, 1H), 7.43-7.47 (m, 1H), 7.05 (s, 1H).Preparation of 4-pyridin-3-yl-thiazol-2-ylamine l-b To a solution of 2-bromo-l-pyridin-3-yl-ethanone Hydrobromide l-a (10 g, 35.58 mmol) in ethanol (100 mL) was added thiourea (2.98 g, 39.21 mmol), K3-pyridyl boronic acid (20mmole), 2-Amino-4-bromo - thiazole (20 mmol) dissolved in Dioxane – water(1:1, 70), then added Potassium carbonate (50 mmol) and replaced three times with argongas . the again add Bis (triphenylphosphine) palladium (II)  dichloride (1mmol) and the reaction was heatedat reflux for 5h. Cooling, the solvent was distilled off under reducedpressure, the residue was dissolved with methylene chloridethen it was driedover anhydrous sodium sulfate and by column chromatography to give 4-(3-pyridyl) -2-aminothiazole 2.5g.[00222j Step 2: Synthesis of 4-(pyridin-3-yl)thiazol-2-amine: To a solution of 2-bromo-1-(pyridin-3-yl)ethanone (2 g, 1 equiv.) in ethanol (18.46 mL), thiourea (0.543 g, 0.7 equiv.) was added. The reaction mixture was heated to reflux for 2 h. After completion of 2 h, the reaction mixture was cooled to 4 C. On cooling the product precipitated out in dihydrobromide salt form. The material obtained was filtered and dried. 4-(pyridin-3-yl)thiazol-2-amine dihydrobromide salt was dissolved in warm water(11 mL) and stirred for 5 mm, to this aqueous ammonium hydroxide solution (17 mL) was added and stirred. The desired product slowly precipitated (yellow solid) which was filtered and dried under vacuum to afford 4-(pyridin-3-yl)thiazol-2-amine 2 g, 56% yield). LCMS m/z 178.01 (M+H); 'H NMR 400 MHz, CD3OD: oe 8.96 (d, J 0.80 Hz, 1H), 8.44 (dd, J= 1.60, 4.80 Hz, 1H), 8.19-8.22 (m, 1H), 7.43-7.47 (m, 1H), 7.05 (s, 1H).To a solution of 3-(bromoacetyl)pyridine hydrobromide R-12 (920 mg, 3.27 mmol) in EtOH (10.0 mL) and H20 (2.0 mL) at room temperature is added thiourea R-11 (250 mg, 3.27 mmol). The reaction mixture is heated at 80 C for 2 hours, allowed to room temperature, and taken to pH8 with NH4OH. The mixture is cooled to 0 C, and filtered to give the title intermediate 1-51 (536 mg).General procedure: To a solution of 2 (11.2 mmol) in 25 ml of ethanol at room temperature was added thiourea (13.4 mmol).The reaction mixture was stirred at room temperature for 1 hour, quenched with water and washed with dichloromethane. The aqueous phase was concentrated in vacuo to give a yellow solid HBr salt. The salt was then dissolved in minimal amount of water and 10% NaOH added drop wise until a white precipitate 3 formed (approximately at pH 8).The precipitate was then filtered and dried.

Molecular Weight:177.23
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:177.03606841
Monoisotopic Mass:177.03606841
Topological Polar Surface Area:80
Heavy Atom Count:12
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes