Reference

Process for the preparation of 4-amino-3-quinolinecarbonitriles and 7-aminothieno[3,2-b]pyridine-6-carbonitriles

Process for the preparation of 4-amino-3-quinolinecarbonitriles and 7-aminothieno[3,2-b]pyridine-6-carbonitriles. Sutherland, Karen Wiggins; Feigelson, Gregg Brian; Boschelli, Diane Harris; Blum, David Michael; Strong, Henry Lee (Wyeth Holdings Corporation, USA). U.S. Pat. Appl. Publ. US 2005043537 A1 24 Feb 2005, 17 pp. (English). (United States of America). CODEN: USXXCO. 92878-95-0 which is the cas registry number of some chemical is mentioned. CLASS: ICM: C07D215-38. APPLICATION: US 2004-918947 16 Aug 2004. PRIORITY: US 2003-PV496191 19 Aug 2003. DOCUMENT TYPE: Patent CA Section: 27 (Heterocyclic Compounds (One Hetero Atom)) Section cross-reference(s): 28, 45 This invention discloses a process for the prepn. of 4-amino-3-quinolinecarbonitriles comprising (1) coupling of amines with cyanoacetic acid to cyanoacetamides; (2) condensation of the cyanoacetamides with anilines in an alc. 92878-95-0 which is the cas registry number of some chemical is mentioned. solvent and a trialkylorthoformate to 3-amino-2-cyanoacrylamides; and (3) cyclization of the 3-amino-2-cyanoacrylamides with phosphorus oxychloride in acetonitrile, butyronitrile, toluene or xylene, to 4-amino-3-quinolinecarbonitriles. For example, amidation of 3-chloro-4-fluoroaniline with cyanoacetic acid in the presence of DIPC or EDCI afforded the corresponding cyanoacetamide in 81% and 94% yield, resp. To a soln. of this compd. (110 g) and 4-bromo-3-ethoxyaniline hydrochloride (100.4 g) in isopropanol (500 mL) was added tri-Et orthoformate (64 mL x 3) in three portions, and the suspension was refluxed to give propenamide I in 70% yield. POCl3 (740 g) was added dropwise to a heated suspension of I (1000 g) in methanol (40 mL) and acetonitrile (7.50 L) over 30 min. The mixt. was then refluxed for 24 h to produce II in 84% yield. Also disclosed is a similar process for the prepn. of 7-aminothieno[3,2-b]pyridine-6-carbonitriles, in which 3-aminothiophenes instead of anilines was used in the above 2nd step. The invented compds. are intermediates for the synthesis of other pharmaceutically useful quinolines and so on. ..

Process for the preparation of 4-amino-3-quinolinecarbonitriles and 7-aminothieno[3,2-b]pyridine-6-carbonitriles

Process for the preparation of 4-amino-3-quinolinecarbonitriles and 7-aminothieno[3,2-b]pyridine-6-carbonitriles. Sutherland, Karen Wiggins; Feigelson, Gregg Brian; Boschelli, Diane Harris; Blum, David Michael; Strong, Henry Lee (Wyeth Holdings Corporation, USA). U.S. Pat. Appl. Publ. US 2005043537 A1 24 Feb 2005, 17 pp. (English). (United States of America). CODEN: USXXCO. 92878-95-0 which is the cas registry number of some chemical is mentioned. CLASS: ICM: C07D215-38. APPLICATION: US 2004-918947 16 Aug 2004. PRIORITY: US 2003-PV496191 19 Aug 2003. DOCUMENT TYPE: Patent CA Section: 27 (Heterocyclic Compounds (One Hetero Atom)) Section cross-reference(s): 28, 45 This invention discloses a process for the prepn. of 4-amino-3-quinolinecarbonitriles comprising (1) coupling of amines with cyanoacetic acid to cyanoacetamides; (2) condensation of the cyanoacetamides with anilines in an alc. 92878-95-0 which is the cas registry number of some chemical is mentioned. solvent and a trialkylorthoformate to 3-amino-2-cyanoacrylamides; and (3) cyclization of the 3-amino-2-cyanoacrylamides with phosphorus oxychloride in acetonitrile, butyronitrile, toluene or xylene, to 4-amino-3-quinolinecarbonitriles. For example, amidation of 3-chloro-4-fluoroaniline with cyanoacetic acid in the presence of DIPC or EDCI afforded the corresponding cyanoacetamide in 81% and 94% yield, resp. To a soln. of this compd. (110 g) and 4-bromo-3-ethoxyaniline hydrochloride (100.4 g) in isopropanol (500 mL) was added tri-Et orthoformate (64 mL x 3) in three portions, and the suspension was refluxed to give propenamide I in 70% yield. POCl3 (740 g) was added dropwise to a heated suspension of I (1000 g) in methanol (40 mL) and acetonitrile (7.50 L) over 30 min. The mixt. was then refluxed for 24 h to produce II in 84% yield. Also disclosed is a similar process for the prepn. of 7-aminothieno[3,2-b]pyridine-6-carbonitriles, in which 3-aminothiophenes instead of anilines was used in the above 2nd step. The invented compds. are intermediates for the synthesis of other pharmaceutically useful quinolines and so on. ..