1-Chloroisoquinoline

white to yellow low melting solid, crystals and/or

Phosphorus oxychloride (200 ml_) was added dropwise under ice-cold condition to isoquinolin-/V-oxide (20.0 g). The reaction mixture was then heated to reflux at 105 °C overnight. Phosphorus oxychloride was evaporated under reduced pressure, then the residue was quenched with ice and extracted with dichloromethane. The organic layer was separated, dried over sodium sulfate and concentrated. The crude was purified by column chromatography on silica gel using ethylacetate and petroleum ether as eluent (21.0 g; 85percent). 1H NMR (400 MHz, DMSO-d6): δ 8.25-8.31 (m, 2H), 8.08 (d, J= 8.0 Hz, 1 H), 7.88-7.91 (m, 2H), 7.80-7.84 (m, 1 H). MS (ESI+): 164.0, HPLC (Method A) Rt 8.29min; HPLC purity 96.0 percentGeneral procedure: To a stirred solution of the appropriate azine N-oxides in anhydrous CH69.3 g of isoquinoline N-oxide (448 mmole) available from Tokyo Kasei Co. and 225 ml of chloroform were introduced into a 1L-three-neck flask to dissolve therein. Then, 219.6 g (1432 mmole) of phosphorous oxychloride was slowly dropped therein and stirred under ice-cooling while maintaining the inner temperature at 15 to 20°C. Thereafter, the temperature was raised, and the mixture was stirred under reflux for 3 hours. The reaction product was left to cool to room temperature, followed by pouring the resultant into an ice water. The mixture was extracted with ethyl acetate, an organic layer was washed with water till it showed neutral pH, and then the solvent was removed under reduced pressure. The residue was purified using silica gel column chromatography (eluent: chloroform/hexane: 5/1), to yield 35.5 g of a white crystal of 1- chloroisoquinoline (44. 9percent yield).General procedure: Ina flask (50 mL) equipped with a magnetic stirrer bar and balloon, a mixture of triphenylphosphine (1191mg, 4.54 mmol) and trichloroisocyanuric acid (360 mg, 1.55 mmol) was heated under an argonatmosphere. During the heating process, triphenylphosphine melted, and trichloroisocyanuric acidvigorously reacted at 130-140 °C to form a dark brown oil, followed by further heating for 10 min.1-Methylquinolin-2(1H)-one (242 mg, 1.50 mmol) was added to the mixture followed by heating at130-140 °C for 3 h. Then, the reaction mixture was dissolved in CH2Cl2 and basified with triethylaminefollowed by silica gel column chromatography using hexane-EtOAc (6:1) as an eluate. The product2-chloroquinoline (204 mg, 82percent) was obtained.

1-Chloroisoquinone is used in the preparation of new aminoisoquinolinylurea derivatives which show antiproliferative activity against melanoma cell lines. It can also be applied to the control of storage and stability of unstable boronic acids.

Molecular Weight:163.60
XLogP3:3.2
Hydrogen Bond Acceptor Count:1
Exact Mass:163.0188769
Monoisotopic Mass:163.0188769
Topological Polar Surface Area:12.9
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes