5-BROMOISOQUINOLIN-1-AMINE

A suspension of5-bromo-1-chloroisoquinoline (2.0 g, 8.25mmol) in sat. NH3-MeOH (100 mL) was heated to180 C for 15days in autoclave. After cooling, the solvent was removed by evapolation. The residue was washed with CH2CI2 then purified on SCX SPE. Formed solid was washed with hexane to give the title compound (1.57 g, 85percent).A suspension of5-bromo-1-chloroisoquinoline (4) (2.0 g, 8.25mmol) in sat. NH3-MeOH (100 mL) was heated to180 C for 15days in an autoclave. After cooling, the solvent was removed by evaporation. The residue was washed withCH2CI2 then purified on SCX SPE. Formed solid was washed with hexane to give the title compound (1.57g, 85 percent). MS (ESI) (M+H)+ 223, 225.Step 3: Into a 500-mL round-bottom flask purged and maintained with an inertatmosphere of nitrogen, was placed a mixture of 5-bromo-1-chloroisoquinoline (17.5 g, 72.16mmol, 1.00 equiv), AcNH2 (85.8 g, 1.45 mol, 20.15 equiv) and potassium carbonate (49.0 g, 354.53 mmol, 4.91 equiv). The mixture was stirred for 3 h at 180 °C then it was cooled to RT and poured into 2000 mL of water with stirring. The solids were collected by filtration toprovide 12.0 g (75percent) of 5-bromoisoquinolin-1-amine as a brown solid.General procedure: Step 1: A glass vial was charged with corresponding bromo-heteroaryl compound (0.20mmol, 1eq), potassium metabisulfite (88mg, 0.40mmol, 2eq), tetrabutylammonium bromide (70mg, 0.22mmol, 1.1eq), sodium formate (15mg, 0.22mmol, 1.1eq), palladium(II) acetate (5mg, 0.02mmol, 0.1eq), triphenylphosphine (16mg, 0.06mmol, 0.3eq), 1, 10-phenanthroline (11mg, 0.06mmol, 0.3eq). After sealing, the vial was flushed with argon for 30min and the reagents were suspended in dry, degassed DMSO (1mL) and the reaction mixture was stirred for 4h at 70C. After cooling to RT N, N-Diisopropylethylamine (70muL, 0.40mmol, 2eq) and a solution of tert-butyl (E)-(2-aminoethyl)(3-(4-(pyridin-3-yl)phenyl)allyl)carbamate (63) (106mg, 0.30mmol, 1.5eq) in dry THF (1mL) were added and the reaction mixture was cooled to 0C. Subsequently a solution of N-bromosuccinimide (62mg, 0.40mmol, 2eq) in dry THF (1mL) was added and the reaction mixture was allowed to come to RT. After stirring for 1h the reaction was quenched by adding H2O (1mL) and brine (2mL). The resulting mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the solvent removed under reduced pressure. The residue was purified via flash-column-chromatography (SiO2, 0% to 5% MeOH in DCM) to yield the desired Boc-protected product, which was used directly in step 2.Step 4: Into a 250-nt round-bottom flask purged and maintained with an inertatmosphere of nitrogen, was placed a mixture of

Molecular Weight:223.07
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:221.97926
Monoisotopic Mass:221.97926
Topological Polar Surface Area:38.9
Heavy Atom Count:12
Complexity:163
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes