BBIQ synthesis

Yield:1229024-57-0 45 mg

Reaction Conditions:

Stage #1: N₄-benzyl-2-chloroquinoline-3,4-diamine;n-valeryl chloridewith triethylamine in tetrahydrofuran at 20; for 6 h;
Stage #2: with ammonia in methanol at 150; for 1 h;Microwave irradiation;

Steps:

Synthesis of 1-benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (3):

To a solution ofcompound 9 (500 mg, 1.59 mmol) in ethyl acetate (20 mL) were added catalytic amount of Pd/C and Na2SO4. The reaction mixture was subjected to the hydrogenation at 55 psi hydrogen pressure for 3 h. After the completion of reaction as monitored by TLC, thereaction mixture was filtered through celite and the filtrate was evaporated under reduce pressure to obtain N4-benzyl-2-chloroquinoline-3,4-diamine (400 mg, crude) as thick liquid.To a solution of N4-benzyl-2-chloroquinoline-3,4-diamine (400 mg, 1.41 mmol) in anhydrous THF were added triethylamine (218 μL, 1.55 mmol) and valeroyl chloride (256μL, 2.11 mmol). The reaction mixture was stirrer at room temperature for 6h. The solventwas removed under reduce pressure and the residue was dissolved in ethyl acetate andwashed with water. The ethyl acetate fraction was dried over sodium sulphate and evaporatedunder vacuum to obtain crude solid which was dissolved in 1 mL of 2M solution of ammoniain MeOH and heated under microwave condition at 150 for 1h in a sealed reaction vessel.The solvent was removed under vacuum, and the residue was purified using silica gel columnchromatography (3% MeOH/dichloromethane) to obtain the compound 3 as a white solid. (45mg, 8%) 1H NMR (400 MHz, CDCl3) δ 7.81 (dd, J = 8.4, 0.8 Hz, 1H), 7.71 (dd, J = 8.3, 0.9Hz, 1H), 7.44 (ddd, J = 8.4, 7.1, 1.3 Hz, 1H), 7.36 - 7.28 (m, 3H), 7.13 (ddd, J = 8.3, 7.1, 1.2Hz, 1H), 7.08 - 7.03 (m, 2H), 5.81 (s, 2H), 5.73 (s, 2H), 2.90 - 2.85 (m, 2H), 1.79 (dt, J =15.5, 7.6 Hz, 2H), 1.48 - 1.38 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H). The 1H NMR was consistentwith that reported in the literature.1 Purity of the target compound 3 was confirmed to bemore than 98% using Waters ACQUITY UPLC H-Class Core System equipped with 2998Photodiode Array Detector coupled with ACQUITY QDa Detector having quaternarypumping configured for flow rates from 0.05-5.0 ml/Min.

References:

Saroa, Ruchika;Kaushik, Deepender;Bagai, Upma;Kaur, Sukhbir;Salunke, Deepak B. [Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,# 9,p. 1099 - 1105] Location in patent:supporting information