6-Bromo-1-(tetrahydro-2H-pyran-4-yl)-1H-benzimidazole

To a solution of compound 5-bromo-Nl-(tetrahydro-2H-pyran-4-yl)benzene-l, 2- diamine (500 mg, 1.852 mmol) in HC(OMe)To a solution of compound 5-bromo-Nl-(tetrahydro-2H-pyran-4-yl)benzene-l, 2- diamine (500 mg, 1.852 mmol) in HC(OMe)3 (2 mL) was added TsOH (15mg, 0.078= mmol). The reaction mixture was stirred at 100 C for 12h. The reaction mixture was extracted with DCM washed with water and the organic layer dried over sodium sulfate which was removed by filtration. After concentration of the filtrate, the crude product was purified by column (201 mg, 38.53%). LCMS (m/z): 281.0, 283.0 (M+l).To a solution of 6-bromo-l-(tetrahydro-2H-pyran-4-yl)-lH-benzo[d]imidazole (200 mg, 0.714 mmol) in dioxane/H20 (1: 1) (8 mL) were added l-(3, 4-dihydroisoquinolin- 2(lH)-yl)-3-(3-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)phenoxy)propan-2-ol (292 mg, 0.714 mmol) Pd(dppf)Cl2 (26 mg, 0.0357 mmol) and K3P04 (454 mg, 2.143 mmol). The reaction mixture was stirred at 100 C under N2 for 12h. After cooling, the reaction mixture was extracted with DCM and water. The combined organic layers were dried over sodium sulfate, filtered and concentrated to yield a crude product which was purified by prep-HPLC to afford the title compound the TFA salt (38 mg, Yield 11.2%). 1H NMR (400 MHz, MeOD): delta 8.39 (s, IH), 8.36 (s, IH), 7.87 (s, IH), 7.75 (d, J=8.4 Hz, IH), 7.57 (d, J=8.4 Hz, IH), 7.42-7.18 (m, 7H), 6.99 (d, J=8.0 Hz, IH), 4.79-4.71 (m, IH), 4.55-4.52 (m, IH), 4.46 (s, 2H), 4.19-4.12 (m, 4H), 3.70 (t, J=11.2 Hz, 2H), 3.61 (t, J=6.4 Hz, 2H), 3.47-3.37 (m, 2H), 3.33 (s, 2H), 3.22-3.18 (m, 2H), 2.28-2.13 (m, 4H). LCMS (m/z): 484.2 (M+l).To a solution of N-(5-bromo-2-nitrophenyl)tetrahydro-2H-pyran-4-amine (600 mg, 1.99 mmol) in HCOOH (10 mL) was added Fe powder (1.3 g, 23.2 mmol). After stirring for 4h at reflux temperature, the mixture was diluted with MeOH (100 mL) and filtered over a Celite pad. The filtrate was concentrated to give the title compound which was directly used for next step without further purification.A mixture of compound 6-bromo-l-(tetrahydro-2H-pyran-4-yl)-lH- benzo[d] imidazole (68 mg, 0.243 mmol), l-(3, 4-dihydroisoquinolin-2(lH)-yl)-3-((4-(4, 4, 5, 5- tetramethyl-l, 3, 2-dioxaborolan-2-yl)pyridin-2-yl)amino)propan-2-ol (100 mg, 0.243 mmol), Pd(dppf)Cl2 (17.8 mg, 0.026 mmol) and K2C03 (101 mg, 0.734 mmol) in H20-dioxane (1 mL/ 3 mL) was stirred at 100C under N2 with microwave mediated heating for 15 min. The solvent was then removed by concentration and the crude product purified by pre-HPLC to give the title compound as the formate salt (11.8 mg, yield: 10.1%). 1H NMR (500 MHz, MeOD): delta 8.44 (s, 1H), 7.98 (s, 1H), 7.90 (d, J = 5.6 Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.63 (d, J = 1.6 Hz, 1H), 7.35-7.27 (m, 3H), 7.21 (d, J = 7.6 Hz, 1H), 7.04-7.02 (m, 2H), 4.82-4.76 (m, 1H), 4.45 (s, 2H), 4.35 (br.s, 1H), 4.18 (dd, J = 4.0, 11.2 Hz, 2H), 3.75-3.52 (m, 6H), 3.33 (br, 2H), 3.23 (br.s, 2H), 2.31-2.15 (m, 4H)ppm; ESI-MS (m/z): 484.3 [M+l] +.

Molecular Weight:281.15
XLogP3:2.4
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:280.02113
Monoisotopic Mass:280.02113
Topological Polar Surface Area:27
Heavy Atom Count:16
Complexity:245
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes