4-(4-Pyridyl)benzoic acid

4-(pyridin-4-yl)benzoic acid; To a solution of 4-boronobenzoic acid (1.66 g, 10 mmol) and 4-bromopyridine (1.72 g, 11 mmol) in acetonitrile (40 mL) and water (40 mL), potassium carbonate (5.5 g, 40 mmol), Bis(triphenylphosphine)palladium(II) chloride (400 mg, 0.37 mmol) was added. The mixture was degassed and purged withed nitrogen. The mixture was stirred at 100° C. for 24 h. Then the hot suspension was filtered and concentrated to half of the original volume and washed with dichloromethane. The aquatic phase was adjusted to pH=3 with hydrochloric acid (1 M) and filtrated, washed with water. The residue was dried in vacuum to obtain 1.8 g of white solid of 4-(pyridin-4-yl)benzoic acid. Yield: 90percent. LC-MS (ESI) m/z: 200 (M+1)2.45b. Compound (III) was partitioned between dichloromethane and aqueous sodium carbonate. The organic phase (containing the free base of (III)) was washed with additional aqueous sodium carbonate and was distilled under reduced pressure and solvent exchanged with dimethylformamide (DMF). This solution was assayed for wt/wt content of (III). To a suspension of (IV) (1.0 equivalent vs. (III)) in DMF were added 2 equivalents of 4-methylmorpholine and 1.1 equivalents of O-Benztriazol-1-yl-N, N, N?, N?-tetramethyluronium tetrafluoroborate (TBTU). This mixture was stirred at ambient temperature until ester activation was complete (about 90 minutes). The DMF solution of Compound (III) (1 equivalent) was added and the resulting solution stirred overnight after which HPLC indicated that the reaction was complete. Water was added at 75° C. and the mixture was cooled to crystallize the product. The mixture was cooled to 5° C., filtered, and the filter cake was washed with water. The product was dried under reduced pressure at 70° C.35.144 mmol of 4-bromopyridine hydrochloride, 35.144 mmol, were weighed separately4-carboxyphenylboronic acid and 10 mmol of sodium carbonate were added to a toluene solution, and 0.08 mmol was addedOf tetraprophenylphosphonium palladium, in the catalyst tetrasthenyl phosphorus palladium under the action, Reaction for 10 h to obtain a white intermediate.The intermediate product is dried, Adding thionyl chloride, inReflux at 80 ° C, After completion of the reaction, the excess solvent was evaporated to dryness to give a yellow solid.The yellow solid was mixed with 5-aminoisophthalic acid in DMF and reacted at room temperature for 3 h. The reaction solution was added to 500 mL of distilled water, Precipitation of a large number of solid, that is, H2PYBI ligand.35.144 mmol of 4-bromopyridine hydrochloride, 35.144 mmol, were weighed separately4-carboxyphenylboronic acid and 10 mmol of sodium carbonate were added to a toluene solution, and 0.08 mmol was addedOf tetraprophenylphosphonium palladium, in the catalyst tetrasthenyl phosphorus palladium under the action, Reaction for 10 h to obtain a white intermediate.The intermediate product is dried, Adding thionyl chloride, inReflux at 80 ° C, After completion of the reaction, the excess solvent was evaporated to dryness to give a yellow solid.The yellow solid was mixed with 5-aminoisophthalic acid in DMF and reacted at room temperature for 3 h. The reaction solution was added to 500 mL of distilled water, Precipitation of a large number of solid, that is, H2PYBI ligand. To a suspension of 4-[pyridin-4-yl]-benzaldehyde (approx. 2.8 g, 15 mmol) (reference example 8a) in t-butanol (100 mL) was added 2-methy-but-2-ene (15 mL) followed by a solution comprised of NaClO2 (14.7 g, tech. grade) and NaH2PO4.H2O (14.7 g, 105 mmol) in H2O (100 mL). This mixture was stirred for 20 min then the precipitated solid filtered off. This solid was washed with water then set aside. The organic phase of the mother liquor was separated then washed with brine, dried over MgSO4 and concentrated to give a solid. This material was combined with the solid obtained by filtration and dried under vacuum to give 2.34 g of the title compound. 1H NMR (DMSO) d 7.77 (d, J=6 Hz, 2H), 7.93 (d, J=8 Hz, 2H), 8.06 (d, J=8 Hz, 2H), 8.70 (d, J=6 Hz, 2H). MS (EI) m/z 199 (M)+.The residue obtained by distilling off the solvent under reduced pressure was suspended in N, N-dimethylformamide (10 ml), followed by the addition of 4-(4-pyridyl)benzoic acid (420 mg) obtained in Referential and N, N-dimethyl-4-aminopyridine (309 mg). Under ice cooling, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (405 mg) was added and the resulting mixture was stirred at room temperature for 68 hours. After concentration, the residue was purified by chromatography on a silica gel column (dichloromethane:methanol=70:1). The colorless solid so obtained was recrystallized from a mixed solvent of ethyl acetate and hexane, followed by recrystallization from ethyl acetate to obtain colorless needle crystals (185 mg). To the filtrate, on the other hand, saturated hydrochloric acid-ethanol (4 ml) was added.In a similar manner to Example 4 except for the use of the resulting residue and 4-(4-pyridyl)benzoic acid as the raw materials, the reaction was conducted, whereby the title compound was obtained. 1H-NMR (DMSO-d6) delta: 1.70-2.10(2H, m), 3.00-3.65(4H, m), 3.75-3.90(1H, m), 7.50-8.40(13H, m), 8.95-9.05(2H, m). MS (FAB) m/z: 492 [(M+H)+, Cl35], 494 [(M+H)+, Cl37].The residue obtained by distilling off the solvent under reduced pressure was suspended in N, N-dimethylformamide (10 ml), followed by the addition of 4-(4-pyridyl)benzoic acid (420 mg) obtained in Referential and N, N-dimethyl-4-aminopyridine (309 mg). Under ice cooling, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (405 mg) was added and the resulting mixture was stirred at room temperature for 68 hours. After concentration, the residue was purified by chromatography on a silica gel column (dichloromethane: methanol = 70:1). The colorless solid so obtained was recrystallized from a mixed solvent of ethyl acetate and hexane, followed by recrystallization from ethyl acetate to obtain colorless needle crystals (185 mg). To the filtrate, on the other hand, saturated hydrochloric acid-ethanol (4 ml) was added.In the same manner as in Example A-4, a reaction was conducted using the resulting residue and 4-(4-pyridyl)benzoic acid as starting materials, whereby the title compound was obtained. 1H-NMR (DMSO-d6) delta: 1.70-2.10(2H, m), 3.00-3.65(4H, m), 3.75-3.90(1H, m), 7.50-8.40(13H, m), 8.95-9.05(2H, m). MS (FAB) m/z: 492 [(M+H)+, Cl35], 494 [(M+H)+, Cl37]. Elementary analysis for C26H22ClN3O3S*HCl*1.8H2O Calculated: C, 55.68; H, 4.78; N, 7.49; Cl, 12.64; S, 5.72. Found: C, 55.62; H, 4.94; N, 7.67; Cl, 12.76; S, 5.79.

Molecular Weight:199.20
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:199.063328530
Monoisotopic Mass:199.063328530
Topological Polar Surface Area:50.2
Heavy Atom Count:15
Complexity:216
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes