7-Chlorothieno[3,2-b]pyridine

Preparation Example 22-3 1-(3-Amino-thiophen-2-yl)-ethanone (423 mg) was dissolved in tetrahydrofuran (30 ml). Ethyl formate (3 ml) and sodium methoxide (640 mg) were added to the solution, and the mixture was stirred at room temperature for 3 hr. Water was added to the reaction mixture, and the organic layer was extracted with methanol/chloroform and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography with a methanol-chloroform system to give 4H-thieno[3, 2-b]pyridin-7-one (95 mg, yield 21percent). 4H-Thieno[3, 2-b]pyridin-7-one (94 mg) was suspended in diisopropylethylamine (2 ml), phosphorus oxychloride (0.5 ml) was added to the suspension, and the mixture was stirred at 100°C for one hr. Water was added to the reaction mixture under ice cooling. The aqueous layer was neutralized with an aqueous sodium hydrogencarbonate solution, and the organic layer was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography with an acetone-chloroform system to give 7-chloro-thieno[3, 2-b]pyridine (84 mg, yield 79percent).The compound 10c (2.5 g, 16 mmol)Dissolved in 5 ml of acetonitrileAdding 2ml of phosphorus oxychloride to 90 for 90min, After the reaction is completed, the temperature is reduced to room temperature and then a large amount of ice is added, Then extracted with ethyl acetate and passed through column chromatography to give 10d (1.5 g, 63percent).7-Chlorothieno[3, 2-6]pyridine (6); To neat POClPreparation 93A: 7-Chlorothieno[3, 2-b]pyridine[00324] A suspension of thieno[3, 2-b]pyridin-7-ol (4.6 g, 30.4 mmol) in POClStep H: Preparation of 7-chlorothienor3, 2-blpyridine: A mixture of thieno[3, 2-b]pyridin-7-ol (2.50 g, 16.5 mmol) and POClA stirred suspension of thieno[3, 2-b]pyridin-7-ol (1, 5.0 g, 33.1 mmol) in POCls(15 mL) was heated to 105°C in an oil bath for 4 hrs. The resultant solution was cooled toroom temperature and the POCls was removed under reduced pressure. The residue wascooled in an ice/water bath and cold water was added. The water was made basic withconcentrated NlrLtOH solution and extracted with EtOAc. The organic extract was driedover anhydrous sodium sulfate and concentrated to produce an oil which was purified bycolumn chromatography (eluent EtOAc-hexane, 1:4) to afford the title compound as abrown solid (4.5 g, 72percent yield). Step 2. 7-Chlorothieno[3, 2-b]pyridine (2) A stirred suspension of thieno[3, 2-b]pyridin-7-ol; (5.0 g, 33.1 mmol) in POClPreparation of N-(3-fluoro-4-(thieno[3, 2-b]pyridin-7-yloxy)phenylcarbamothioyl)-2-phenylacetamide; Step A: Preparation of 7-chlorothieno[3, 2-b]pyridine; To a stirred solution of POCl[001237] (i) Production of 7-chlorothieno[3, 2-b]pyridine[001238] A mixture of thieno[3, 2-b]pyridin-7-ol (3.8 g, 25 mmol) and phosphorus oxychloride (18 g, 120 mmol) was stirred at 105A 2-L, 3-neck, rb flask equipped with a mechanical overhead stirrer, a 250-mL addition funnel, and a thermocouple w/NThieno [3, 2, b] pyridin-7-ol (200 mg; 1.32 mmol) was added to thionyl chloride (1.57 g; 13.2 mmol), followed by a drop of DMF. The solution was stirred at 80°C for 4 hours. The cooled solution was diluted with ethyl acetate and neutralised to pH 7 with a saturated solution of sodium hydrogen carbonate (25 ml). The organic layer was washed with brine, dried and concentrated to yield the title compound (112 mg; 50percent); Mass Spectrum: M+H 170.

Molecular Weight:169.63
XLogP3:2.6
Hydrogen Bond Acceptor Count:2
Exact Mass:168.9752980
Monoisotopic Mass:168.9752980
Topological Polar Surface Area:41.1
Heavy Atom Count:10
Complexity:131
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes