1-chloro-5-nitro-isoquinoline

General procedure: To a stirred solution of the appropriate azine N-oxides in anhydrous CHTo a solution of 1-chloroisoquinoline (3.6 g, 22.09 mmol) in conc. HGeneral procedure: 6-methyl-5-nitroisoquinoline (46.5 g, 0.228 mol) obtained in General procedure: 6-methyl-5-nitroisoquinoline (46.5 g, 0.228 mol) obtained in above was dissolved in 1, 2-dichloroethane (1.8 L), and added with POCl3 (107 mL, 1.14 mol) at room temperature. The reaction solution was refluxed for 7 hours or more. The reaction solution was cooled to room temperature, and the reaction solution was concentrated by distilling the solvent under reduced pressure. The concentrated solid was dissolved in dichloromethane, and then, an ice water was added thereto. The reaction mixture was subjected to extraction with dichloromethane. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrated solid was added with a mixed solution of ethyl acetate/hexane = 1/1 (v/v), followed by stirring for 2 hours or more at room temperature. The resulting solid was filtered under reduced pressure, and washed with a mixed solution of ethyl acetate/hexane = 1/1 (v/v). The filtered solid was dried with warm wind in an oven (40C) for 3 hours or more to obtain the title compound (28 g, 55%). 1H-NMR Spectrum (300 MHz, DMSO-< 6): delta 8.53 (m, 2H), 7.92 (d, 1H), 7.67 (d, 1H), 2.72 (s, 3H).[Reference Example 51] (0532) (0533) The mixture of 237 mg of [Reference Example 113] (0657) (0658) The mixture of 100 mg of Intermediate 55; Preparation of 1-chloroisoquinolin-5-amine; 1-Chloro-5-nitroisoquinoline.; A mixture of 1-chloroisoquinoline (6.0 g, 0.037 mol) in conc. H2SO4 (35 mL) was treated with a solution of fuming HNO3 (10 mL) and potassium nitrate (4.0 g, 0.040 mol) in conc. H2SO4 (35 mL) at 0-5 C. The mixture was stirred at 0 C. for a further 90 min, and then poured into ice. The precipitate was collected, washed and dried to give the product as a yellow solid. LC-MS: 3.68 min, 209.2 & 211.1 (M+1).Intermediate 18 Preparation of 1-chloroisoquinolin-5-amine; To a 500 mL 3-neck round-bottomed flask containing 1-Chloroisoquinoline (6.50 g, 39.8 mmol), was added H2SO4 (10.59 mL, 198.8 mmol), the mixture was heated to 600C, with stirring under inert atmosphere. After 5 minutes, Potassium Nitrate (2.01 g, 19.9 mmol) was added and the mixture was stirred an additional 5 minutes. The heat source was removed, and the mixture was stirred for 5 minutes before it was cooled to 0 0C in an ice bath. Fuming Nitric Acid (8.41 mL, 198.8 mmol) was added into the mixture drop-wise by addition funnel over 20 minutes, while the reaction mixture was kept cold in ice bath. After the addition, the mixture was allowed to slowly warm to ambient temperature overnight. Then water was added to the mixture (200 mL), and stirred an additional 30 minutes. The solid was collected by filtration. After drying in a reduced-pressure oven for 6 hours, a light yellow powder was recovered, which was titled product (8.2 g, 39.3 mmol). MS (ESI pos. ion) m/z: 209 (M+H). Calc'd Exact Mass for C9H5N2O2Cl: 208.5To a solution of 1-chloroisoquinoline (3.6 g, 22.09 mmol) in conc. H2SO4 (24 mL) was added conc. HNO3 (8 mL) drop wise at 0-5 C. Then KNO3 (2.90 g, 28.71 mmol) was added to the reaction mixture portion wise at 0-5 C. The reaction mass was stirred at rt for 2 h and diluted with water then the reaction mixture was filtered. The filter cake was dissolved in 5% methanol in chloroform and was dried over Na2SO4. The organic layer was filtered and concentrated to afford 4.0 g of the title product. 1H NMR (300 MHz, DMSO-d6): delta 8.74 (t, J=6.9 Hz, 2H), 8.55 (d, J=6.3 Hz, 1H), 8.32 (d, J=6.0 Hz, 1H), 8.02 (t, J=8.1 Hz, 1H).

Molecular Weight:208.60
XLogP3:2.9
Hydrogen Bond Acceptor Count:3
Exact Mass:208.0039551
Monoisotopic Mass:208.0039551
Topological Polar Surface Area:58.7
Heavy Atom Count:14
Complexity:231
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes