With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1082674-24-5,6-Bromoisoquinoline-1-carbonitrile,as a common compound, the synthetic route is as follows.
Pd2dba3 (0.094 g, 0.10 mmol), BINAP (0.19 g, 0.31 mmol) and CS2CO3 (3.3 g, 10.3 mmol) were added to a degassed solution of 6-bromoisoquinoline-1 -carbonitrile (0.8 g, 3.4 mmol) in toluene (10 mL) followed by the addition of B5 (0.52 g, 3.8 mmol) under nitrogen atmosphere. The resulting reaction mixture was irradiated in a microwave at 1 10 C for 20 minutes. The reaction mixture was cooled to room temperature, diluted with EtOAc, filtered and the filtrate was washed with water. The organic layer was separated and the aqueous layer was extracted with EtOAc. The organic layers were combined, dried over Na2S04 and evaporated under reduced pressure to afford the crude mixture which was chromatographed on silica gel (100 – 200 mesh) using 25% EtOAc in petroleum ether to give B6 as a light brown solid (0.25 g, 25%). Rf: 0.4 (25% EtOAc/petroleum ether). Racemic: LCMS m/z = 288.1 (M + H). 1H NMR (300 MHz, CDCI3): delta 1.41 (d, J = 6.3 Hz, 3H), 2.27 – 2.38 (m, 1 H), 2.71 – 2.79 (m, 1 H), 3.30 – 3.38 (m, 1 H), 3.50 – 3.58 (m, 1 H), 4.38 – 4.44 (m, 1 H), 7.67 (d, J = 2.1 Hz, 1 H), 7.71 (dd, J = 2.1 , 9.3 Hz, 1 H), 7.83 (d, J = 5.7 Hz, 1 H), 8.35 (d, J = 9 Hz, 1 H), 8.61 (d, J = 5.7 Hz, 1 H). The racemic compound was chromatographed for enantiomeric separation. Conditions: Column: CHIRAL PAK IA, 4.6 X 250mm, 5 muGammaeta; Column ID: ANL_CHIR IA_145; Mobile Phase: A = hexane, B = isopropyl alcohol; ISOCRATIC: 60:40; FLOW: 0.8 mL/min; Column Temp: 25C; Eluent: EtOH Enantiomer of 8: Chiral HPLC purity: 99.38 % (retention time 12.55 minutes) LCMS m/z = 287.9 (M + H). 1 H NMR (300 MHz, cf6-DMSO): delta 1.30 (d, J = 6.3 Hz, 3H), 2.10 – 2.17 (m, 1 H), 2.65 – 2.76 (m, 1 H), 3.51 – 3.55 (m, 1 H), 3.70 – 3.79 (m, 1 H), 4.50 – 4.57 (m, 1 H), 7.81 (d, J = 2.1 Hz, 1 H), 7.87 (dd, J = 2.7, 9.0 Hz, 1 H), 8.20 (d, J = 5.4 Hz, 1 H), 8.28 (d, J = 9.0 Hz, 1 H), 8.64 (d, J = 5.7 Hz, 1 H)., 1082674-24-5
1082674-24-5 6-Bromoisoquinoline-1-carbonitrile 77174826, aisoquinoline compound, is more and more widely used in various fields.
Reference£º
Patent; PFIZER INC.; CHEKLER, Eugene Lvovich Piatnitski; GILBERT, Adam Matthew; UNWALLA, Rayomand Jal; VERHOEST, Patrick Robert; ANDERSON, James Thomas; WO2015/181676; (2015); A1;,
Isoquinoline – Wikipedia
Isoquinoline | C9H7N – PubChem