7-Chloro-1,2,3,4-tetrahydro-5H-1-benzozepin-5-one

Reference Preparation of 7-chloro-2, 3, 4, 5-tetrahydro-lH-l-benzazepin-5- one; 7-Chloro- l-p-toluenesulfonyl-2, 3, 4, 5-tetrahydro- IH- 1-benz- azepin-5-one (5 g) is added to 90 percent(w/w) sulfuric acid (50 ml), and the mixture is stirred at 0Reference Preparation of 7-chloro-2, 3, 4, 5-tetrahydro-lH-l-benzazepin-5- one; 7-Chloro- l-p-toluenesulfonyl-2, 3, 4, 5-tetrahydro- IH- 1-benz- azepin-5-one (5 g) is added to 90 %(w/w) sulfuric acid (50 ml), and the mixture is stirred at 00C to 100C for 2.5 hours. The reaction mixture is added to a cool water (50 mL) and then is neutralized by gradually adding thereto a solution of sodium hydroxide (75 g) in an appropriate amount of water with attention to exothermal reaction. The reaction mixture is cooled to 25C, and the resulting yellowish green suspension is extracted with toluene (50 mL), and the organic layer is separated, washed with water (25 ml x 2) and dried over sodium sulfate. After filtering off sodium sulfate, the filtrate is concentrated under reduced pressure to give a pale yellow crystals. The crystals are subjected to azeotropic dehydration with toluene in order to remove a slight amount of water to give 7-chloro-2, 3, 4, 5-tetrahydro-lH-l-benzazepin-5-one having a moisture content of less than 100 ppm (2.5 g, yield 89 %, M. p. 103-1040C). The.7-chloro-2, 3, 4, 5-tetrahydro-lH-l-benzazepin-5-one is further recrystallized from methanol/water (7 : 3) to give pale yellow needles.The 7-chloro-2, 3, 4, 5-tetrahydro-lH-l-benzazepin-5-one thus obtained has the following physical data; (1) NMR spectrum data, (2) IR spectrum data, (3) MS spectrum data. (1) NMR spectrum: iH NMR (300MHz, CDCl3): 6= 2.18 (tt, J=7.1Hz, J=6.6Hz, 2H), 2.82 (t, J=7.1Hz, 2H), 3.25 (td, J=6.6Hz, J=4.6Hz, 2H), 4.62 (br s, IH), 6.69 (d, J=8.7Hz, IH), 7.17 (dd, J= 8.7Hz, J=2.5Hz, IH), 7.68 (d, J=2.5Hz, IH) (2) IR spectrum IR (KBr): 3365, 2963, 2933, 1655, 1607, 1287, 842, 820 cm-1 EPO (90.0 g, 460.0 mmol) and acetonitrile (630 ml) were added and dissolved in a 1 L reactor rear, Magnesium hydroxide (134.16 g, 2300 mmol) was added to the reaction mixture at 10 C. or lower, and the mixture was stirred for 30 minutes. While maintaining the temperature, 2-methyl-4-nitrobenzoyl chloride (110.17 g, 552.0 mmol) was slowly added to the reaction mixture and stirred for 5 hours. The reaction mixture was filtered to remove magnesium hydroxide, distilled water (1.35 L) and dichloromethane (0.9 L) were added and the layers were separated to obtain an organic layer. Distilled water (1.5 L) was added to the obtained organic layer, the pH of the reaction mixture was adjusted to pH 9.5 to 10 using an aqueous sodium hydroxide solution, dichloromethane (200 ml) was added, stirred And the organic layer was separated. The obtained organic layer was dried over sodium sulfate (Na 2 SO 4), filtered and concentrated under reduced pressure to give 7-chloro-1- (2-methyl-4-nitrobenzoyl) -5-oxo- , 156.79 g of 5-tetrahydro-1 H-1-benzazepine (yield: 95%).A solution of 10 g (0.051 mol) of Preparation of 7-chIoro-l-(2-methyl-4-nitrobenzoyl)-5-oxo-2, 3, 4, 5-tetrahydro-lH-l- benzazepine7-Chloro-5-oxo-2, 3, 4, 5-tetrahydro-lH-l -benzazepine (160 gm) as obtained in was dissolved in methylene dichloride (480 ml) and then added aqueous sodium bicarbonate solution (20%, 68.75 gm). The reaction mixture was then cooled to 0 to 5C and then added 2-methyl-4-nitrobenzoylchloride (180 gm) slowly. The pH of the reaction mass was adjusted to 7.0 to 8.0 with aqueous sodium bicarbonate solution (170 ml). The layers were separated and the aqueous layer was extracted with methylene chloride. The solvent was distilled off under reduced pressure to obtain a residual mass. To the residual mass was dissolved in isopropyl alcohol (7300 ml) and maintained for 2 hours at reflux temperature. The separated solid was filtered and dried to obtain 250 gm of 7-chloro-l-(2-methyl-4-nitrobenzoyl)-5-oxo-2, 3, 4, 5-tetrahydro-lH-l-benzazepinePreparation of 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2, 3, 4, 5-tetrahydro-1H-1-benzazepine 7-Chloro-5-oxo-2, 3, 4, 5-tetrahydro-1H-1-benzazepine (160 gm) as obtained in was dissolved in methylene dichloride (480 ml) and then added aqueous sodium bicarbonate solution (20%, 68.75 gm). The reaction mixture was then cooled to 0 to 5 C. and then added 2-methyl-4-nitrobenzoylchloride (180 gm) slowly. The pH of the reaction mass was adjusted to 7.0 to 8.0 with aqueous sodium bicarbonate solution (170 ml). The layers were separated and the aqueous layer was extracted with methylene chloride. The solvent was distilled off under reduced pressure to obtain a residual mass. To the residual mass was dissolved in isopropyl alcohol (7300 ml) and maintained for 2 hours at reflux temperature. The separated solid was filtered and dried to obtain 250 gm of 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2, 3, 4, 5-tetrahydro-1H-1-benzazepine.In a magnetic mixer, a 100 mL four-neck round bottom flask with a thermometer and reflux condenser.Add 4.0 g of In a magnetic mixer, a 100 mL four-neck round bottom flask with a thermometer and reflux condenser.Add 4.0 g of In a 250 mL four-neck round bottom flask equipped with a magnetic stirrer, thermometer and reflux condenser, add 7-chloro-Methyl 5-oxo-1-p-toluenesulfonyl-2, 3, 4, 5-tetrahydro-1H-1-benzazepine-4-carboxylate 8.1 g, concentrated sulfuric acid20.0g, reacted at 50 C for 2 hours, TLC confirmed that the conversion of the raw materials was completed, and then dropped 20 mL of water, a large amount of gas escaped, and the temperature was increased after the addition.After reacting at 80 C for 1 h, TLC confirmed that the conversion was complete, and then added saturated aqueous sodium carbonate solution, and washed by filtration to obtain the compound of formula III.3.3 g, pale yellow solid, mp 101.0 to 102.0 C, yield 84.6%.

Molecular Weight:195.64
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:195.0450916
Monoisotopic Mass:195.0450916
Topological Polar Surface Area:29.1
Heavy Atom Count:13
Complexity:207
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes