5-(4-Bromophenyl)-1-methyl-1H-pyrazole

4-bromoacetophenone (20.0 g; 0.10 mole) and N, N-dimethylformamide dimethylacetal (28.5 mL; 0.20 mole) were mixed together in DMF (12 mL) and heated to 110General procedure for the synthesis of N2To a stirred solution of Ni (1.20 g, 5.10 mmol) in anhydrous THF (10 mL) was added NaH (240 mg, 6.00 mmol, 60% dispersion in mineral oil), the resulting mixture was stirred at 0 C for 1 hour, then n-BuLi (2.3 mL, 5.75 mmol, 2.5 M in hexane) was added into above mixture at -70 C and stirred at -70 C for 1 hour, freshly distilled DMF (1.85 g, 25.3 mmol) was added into above mixture and stirred at -70 C for 1 hour, then the reaction mixture was allowed to warm to 0 C. TLC showed the reaction was completed. The reaction was quenched with water (30 mL) at 0 C, extracted with EtOAc (30 mLx3). The combined organic phase washed with brine (50 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford a residue. The residue was purified by flash column chromatography (eluted: PE/EtOAc=2/1) to afford N2.(2) 3-(4-bromophenyl)-1-methylpyrazole and Intermediate A4 6-methoxy-2-(4-( 1 -methyl- 1 H-pyrazol-3 -yl)phenyl)-3.4-dihydroisoquinolin- 1 (2H)-one and 6-methoxy-2-(4-(l -methyl- lH-pyrazol-5-yl)phenyl)-3.4-dihydroisoquinolin-l(2H)-one Step 1 : 3-(4-bromophenyl)-lH-pyrazole (0.377 g, 1.690 mmol) was dissolved in THF (8.45 ml). 60% Sodium hydride in oil (0.101 g, 2.54 mmol) was added and the reaction was stirred at rt for 15 min. Methyl iodide (0.116 ml, 1.859 mmol) was added and the reaction was stirred overnight at room temperature. The reaction was quenched with water and extracted three times with dichloromethane. The organic layers were combined, passed through a phase separator and concentrated. The crude material was purified via silica gel chromatography using 0-50% ethyl acetate in heptanes to afford a 2: 1 mixture of products (370 mg, 1.561 mmol, 92 % yield) as a yellow solid. NMR (400 MHz, CHLOROFORM-^ delta ppm 3.86 - 3.95 (m, 3 H), 3.97 (s, 6 H), 6.34 (d, J=1.52 Hz, 1 H), 6.54 (d, J=2.02 Hz, 2 H), 7.30 - 7.33 (m, 2 H), 7.40 (d, J=2.53 Hz, 2 H), 7.49 - 7.56 (m, 5 H), 7.59 - 7.64 (m, 2 H), 7.66 - 7.72 (m, 4 H). LC MS (m/z, MH+): 238.9.In a 40 ml vial, bromo derivative (236 mg, 1.06 mmol, 1.0 eq.), bispinacolotodiboron (253.6 mg, 1.06 mmol, 1.0 eq.), Pd(dppf)CI2 (86.4 mg, 0.106 mmol, 0.1 eq.) and potassium acetate (321.8 mg, 3.17mmol, 3.0 eq.) were mixed in dioxane (10 ml) and heated to 80 C for 48 hours. LCMS indicated that the product was formed in major amount. . The crude reaction was purified in the presence of silica (10-15 gm) and purified using hexanes: ethyl acetate (0-100%) to yield desired boron ester. Theproduct was characterized by reverse phase HPLC using method 4. (ES, m/z) [M +H+] 284.9. Retention time = 1.42 mins

Molecular Weight:237.10
XLogP3:2.6
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:235.99491
Monoisotopic Mass:235.99491
Topological Polar Surface Area:17.8
Heavy Atom Count:13
Complexity:166
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes