6-PHENYL-PYRIDIN-2-YLAMINE

General procedure: To a solution of the requisite chloro-amino-substituted heteroaromatic in anhydrous 1, 4-dioxane (30 volumes wrt chloride) in a sealed tube was introduced phenylboronic acid (1.5 equiv) and finely ground potassium phosphate (2.0 equiv). The solution was degassed (NGeneral procedure: To a solution of the requisite chloro-amino-substituted heteroaromatic in anhydrous 1, 4-dioxane (30 volumes wrt chloride) in a sealed tube was introduced phenylboronic acid (1.5 equiv) and finely ground potassium phosphate (2.0 equiv). The solution was degassed (N2 bubbling) for 5 min, Pd(OAc)2 (5 mol % wrt chloride) and di-tert-butylphosphinoferrocene (5 mol % wrt chloride) introduced and degassing continued for a further 5 min. The tube was sealed under nitrogen and heated with rapid stirring at 100 C for 5 h. After cooling, the reaction mixture was filtered in vacuo through a celite pad and the precipitated material washed with 1, 4-dioxane. The combined filtrates were evaporated and purified by flash column chromatography (neat hexane to 1:1 hexane/EtOAc gradient containing 2.5% by volume Et3N) to furnish the biarylanilines 13, 14 and 15.General procedure: A mixture of A -X (as provided in Table 3, 10 mmol, 1.0 equiv), phenylboronic acid (as provided in Table 3), Pd(OAc)2 (0.4 mmol, 0.04 equiv) and H20 (25 mL, 1384 mmol) in a 3 -neck round-bottom flask was stirred under reflux at 100 C in a N2 atmosphere for the time listed in Table 1. The initial and final pH values of the aqueous phase were measured before and after the heating was enabled when the temperature was stabilized at 25 - 27 C, and listed in Table 3. The initial reaction time (t = 0) was taken when the reaction mixture reached an internal temperature of 100 C; the time to reach this temperature was approximately 20 - 30 minutes. The reactions were biphasic with an aqueous phase and a solid phase. The cooled reaction mixture was basified to pH > 12 using 30% NaOH aqueous solution, and then was thoroughly extracted with ethyl acetate. The combined organic phase is dried over anhydrous MgSC , filtered, and then concentrated in vacuo. The crude product was analyzed by GC and 1H NMR, as provided in Table 3.To a solution of 2-(tert-butoxycarbonylamino)acetic acid (1 13.21 mg, 646.26 mitioI), DIPEA (303.73 mg, 2.35 mmol) and HATU (245.73 mg, 646.26 mitioI) in DCM (2.0 ml_) was added 6- phenylpyridin-2-amine (100.0 mg, 587.51 pmol), and the mixture was stirred at 20 C for 2 hr. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate=5:1 to 2:1 ) to give intermediate i-55a as a light yellow oil. 1 H NMR (400MHz, CDCIs) d 8.48 (s, 1 H), 8.14 (d, J= 8 Hz, 1 H), 7.96 (d, J= 7.2 Hz, 2H), 7.82-7.78 (m, 1 H), 7.52-7.45 (m, 4H), 5.22-5.21 (m, 1 H), 4.03 (s, 2H), 1 .52 (s, 9H) ppm. LCMS (ESI) m/z: [M+H]+ = 328.0.

A derivative of 2-aminopyridinium as potent antimalarial.

Molecular Weight:170.21
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:170.084398327
Monoisotopic Mass:170.084398327
Topological Polar Surface Area:38.9
Heavy Atom Count:13
Complexity:152
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes