1,6-DICHLORO-ISOQUINOLINE

A solution/suspension of 4, 4, 5, 5-tetramethyl-2-(10-methylfluoranthen-8-yl)-1, 3, 2-dioxaborolane (26.6 g, 78 mmol), (4.80 g, 24.2 mmol), 2, 6-dimethyl-8-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)benzofuro[2, 3-b]pyridine (8.22 g, 25.4 mmol), sodium carbonate (6.42 g, 60.6 mmol), palladium tetrakis (0.84 g, 0.73 mmol), 160 mL dimethoxyethane (DME) and 40 mL of water were combined in a round bottom flask. A condenser was attached and then the system was evacuated and purged with nitrogen three times. The reaction mixture was heated to a vigorous reflux overnight. The reaction mixture was diluted with ethyl acetate and water, the suspension was then filtered through Celite and washed with ethyl acetate. The aqueous portion was partitioned off and the organic was washed once with brine, dried with sodium sulfate, filtered, and concentrated down to beige solid. The Celite was further washed with 50/50 DCM/THF and the filtrate was concentrated and combined with the other crude sample. The combined crude sample was dissolved in DCM and purified with silica gel using DCM to 85/15 DCM/ethyl acetate solvent system to get a pale beige solid. The pale beige solid was triturated in 90/10 heptane/ethyl acetate, then filtered to get a white precipitate of 8-(6-chloroisoquinolin-1-yl)-2, 6-dimethylbenzofuro[2, 3-b]pyridine (7.8 g, 91% yield). (4.80 g, 24.2 mmol), 2, 6-dimethyl-8-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)benzofuro[2, 3-b]pyridine (8.22 g, 25.4 mmol), sodium carbonate (6.42 g, 60.6 mmol), palladium tetrakis (0.84 g, 0.73 mmol), 160 mL dimethoxyethane (DME) and 40 mL of water were combined in a round bottom flask. A condenser was attached and then the system was evacuated and purged with nitrogen three times. The reaction mixture was heated to a vigorous reflux overnight. The reaction mixture was diluted with ethyl acetate and water, the suspension was then filtered through Celite and washed with ethyl acetate. The aqueous portion was partitioned off and the organic was washed once with brine, dried with sodium sulfate, filtered, and concentrated down to beige solid. The Celite was further washed with 50/50 DCM/THF and the filtrate was concentrated and combined with the other crude sample. The combined crude sample was dissolved in DCM and purified with silica gel using DCM to 85/15 DCM/ethyl acetate solvent system to get a pale beige solid. The pale beige solid was triturated in 90/10 heptane/ethyl acetate, then filtered to get a white precipitate of 8-(6-chloroisoquinolin-1-yl)-2, 6-dimethylbenzofuro[2, 3-b]pyridine (7.8 g, 91% yield).1, 6-Dichloroisoquinoline A mixture of 6-chloroisoquinoline 2-oxide (1.0 g, 5.58 mmol) and POCl3 (10 mL) was heated to reflux for 4 h. After cooled down to RT, the reaction mixture was poured into ice-water, and extracted with dichloromethane. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford the desired crude product which was used in the next step without further purification.A mixture of 6-chloroisoquinoline 2-oxide (1.0 g, 5.58 mmol) and POC13 (10 mL) was heated to reflux for 4 h. After cooled down to RT, the reaction mixture was poured into ice-water, and extracted with dichloromethane. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford the desiredcrude product which was used in the next step without further purification.To a stirred solution of 1 , 6-dichloroisoquinoline (500 mg, 2.56 mmol)DMSO (5 mL) at RT, piperazine-2-carboxamide (425.6 mg, 2.56 mmol) and K2C03 (1.05 g, 7.68 mmol). The reaction mixture was heated at 80C for 5 h. The reactionmixture was diluted with ethyl acetate and washed with brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash colunm chromatography on silica gel (ethyl acetate/petroleum ether1:5) to afford the desired product (80 mg, 12% yield). ESI-MS m/z: 291[M + H].4-(6-Chloroisoquinolin-1-yl)piperazine-2-carboxamide To a stirred solution of

Molecular Weight:198.05
XLogP3:3.7
Hydrogen Bond Acceptor Count:1
Exact Mass:196.9799046
Monoisotopic Mass:196.9799046
Topological Polar Surface Area:12.9
Heavy Atom Count:12
Complexity:163
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes