6-Bromo-1-isoquinolinamine

6-bromoisoquinolin-1-amineA mixture of 6-bromo-1-chloro-isoquinoline (250 mg, 1 .03 mmol), acetamide (1 .18 g, 20.1 mmol) and K2CO3 (1.38 g, 10.0 mmol) was heated at 180°C for 5 h. The reaction mixture was then allowed to cool to r.t. and diluted with EtOAc and H2O. The organic layer was separated, dried (Na2S06-bromoisoquinolin-1-amine (500 mg, 2.24 mmol) was dissolved in DMF (5 mL), Pd(PPh3)4 (260 mg, 0.22 mmol) added and N2 bubbled through the solution for 10 mins. Zn(CN)2 (157 mg, 1 .34 mmol) was added and the reaction mixture heated in the microwave for 1 hour at 120C. Water and EtOAc were added, the layers separated and the aqueous layer extracted withEtOAc twice. The combined organic layers were washed with brine, passed through a phase separator and solvent removed in vacuo. The crude product was purified by column chromatography (biotage, 25g SNAP cartridge, 0-100% EtOAc in hexane followed by 0-20% MeOH in EtOAc). The solvent was removed to give 1-amino-isoquinoline-6-carbonitrile (293 mg, 77%) as a yellow solid.AnalpH9_MeOH_4MIN: Rt: 2.12 mi mlz 170.1 [M+H]To a solution of compound 51.7 (7 g, 31.4 mmol, 1 eq) in DMF (70 mL) was addedNaH (1.26 g, 31.4 mmol, 60% suspension in mineral oil, 1 eq) portion-wise at 0 C under N2.The mixture was stirred at 0 C for 30 mins, then the mixture was added CH3I (6.68 g, 47.1 mmol, 2.93 mL, 1.5 eq) in one portion, and heated to 25 C and stirred for 1.5 hours. The reaction mixture was quenched by addition of H20 (70 mL) and then was extracted with EtOAc (70 mL x 3). The combined organic layers were washed with H20 (70 mL x 3), andthen with brine (70 mL), dried over Na2SO4, filtered and concentrated. This residue was purified by medium pressure liquid chromatography (MPLC) (Si02, petroleum ether/ethyl acetate=10/1 to 0:1)to give compound 51.5 (2.8 g, 11.81 mmol, 38% yield) as an orange solid and to give compound 51.6 (1.09 g, 4.34 mmol, 14% yield) as yellow oil. 'HNIVIR (400 MFIz, chloroform-cl) oe: 8.03 (d, J5.70 Hz, 1 H), 7.82 (d, J1.75 Hz, 1 H), 7.56 - 7.61 (m, 1H), 7.47-7.53 (m, 1 H), 6.82 (d, J=5.70 Hz, 1 H), 5.33 (br s, 1 H), 3.58 (s, 1 H) and 3.15 (d, J=4.82 Hz, 3 H) ppm.

Molecular Weight:223.07
XLogP3:2.6
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