2-(3-AMINOPHENYL)PYRIDINE

REFERENCE EXAMPLE 31; 2-(3-Aminophenyl)pyridine; To a suspension of 2-bromopyridine (0.5 g, 3.2 mmol), 3-aminophenylboronic acid (0.49 g, 3.2 mmol), anhydrous KGeneral procedure: Aryl halide (1.0 mmol), phenylboronic acid (1.1 mmol), K2CO3(2.0 mmol), Ni7–Pd3BIHPS (0.03 g) and H2O/DMF (2:1, 3 mL) were mixed and heated at 80 °C for anappropriate time (monitored by TLC). Then, hydrazinehydrate (80 wtpercent, 6 eq) was added to the reaction vessel.After completion of the reduction process, the mixturewas filtered and washed with water. The organic layer wasextracted with ethyl acetate (3 × 15 mL) and dried overMgSO4.Then the organic solution was concentrated andpurified by column chromatography to obtain the finalproduct.To a 500 ml round bottom flask was added 20.0 g (116 mmol) of 3-bromoaniline, 85.6 g (233 mmol) of 2- (tributylstannyl) pyridine, 1.34 g (116 mmol) of tetrakistriphenylphosphine palladium, 200 ml of toluene was added and the mixture was refluxed for 12 hours.After completion of the reaction, the temperature was cooled down to room temperature.The organic layer was extracted with ethyl acetate and water and concentrated under reduced pressure.Column purification was carried out using ethyl acetate and n-hexane as eluent. (12.7 g, yield 64percent).(i) REFERENCE EXAMPLE 31; Step A: 2-Bromopyridine (2.00 mL), 3-aminophenylboronic acid (5.40 g) and palladium tetrakistriphenylphosphine (1.2512 g) were added to a mixture of 130 mL of dimethoxyethane and 32 mL of 2.0 M aqueous potassium carbonate under an atmosphere of dry N2. The reaction mixture was heated at 90 C. overnight. The reaction mixture was then cooled to room temperature and diluted with water (300 mL). The resulting precipitate was collected, washed with water and air-dried. The dried material was purified using silica gel chromatography to give 2.75 g of 2-Bromopyridine (2.00 mL), 3-aminophenylboronic acid (5.40 g) and palladium tetrakistriphenylphosphine (1.2512 g) were added to a mixture of 130 mL of dimethoxyethane and 32 mL of 2.0 M aqueous potassium carbonate under an atmosphere of dry N2. The reaction mixture was heated at 90 C overnight. The reaction mixture was then cooled to room temperature and diluted with water (300 mL). The resulting precipitate was collected, washed with water and air-dried. The dried material was purified using silica gel chromatography to give 2.75 g of Step F: Preparation of 3-(2-pyridinyl)benzenamine; To a solution of 2-bromopyridine (1.6 g, 10 mmol) in dimethoxyethane (50 mL) and water (17 mL) was added 3-aminophenylboronic acid hemisulfate (1.86 g, 10 mmol), sodium carbonate (5.6 g, 52.8 mmol) and tetrakis (triphenylphosphine) palladium (0) (0.3 g). The mixture was heated to reflux for 5 hours and then allowed to cooled to room temperature. Brine (50 mL) was added, and the mixture was extracted with ethyl acetate (3 x 25 mL). The organic extracts were dried (MgS04) and concentrated to leave the crude product. The crude product was purified by flash column chromatography to provide the title compound as a thick yellow oil (1.1 g). 11-1 NMR (CDC13) 8 8.6 (m, 1H), 7.69 (m, 2H), 7. 3 (m, 4H), 6.8 (m, 1H), 3.8 (br s 2H).General procedure: The general procedure for the preparation of N-(3-phenyl)-2, 2-dichloroacetamide heterocyclic derivatives was as follows. A mixture of 1 mmol aryl(heterocyclic) bromide, 1.5 mmol 3-aminophenylboronic acid, 2 mmol K2CO3, Triphenyl phosphine at 0.4 mmol and palladium acetate at 0.1 mmol were stirred in 6 mL toluene and 6 mL ethanol at 60' under an argon atmosphere. The progress of the reaction was monitored by TLC (petroleum ether/ethyl acetate). After the reaction finished, the reaction mixture was filtered. The filtrate was concentrated to dryness and subjected to flash column chromatography (silica gel), eluting with petroleum ether/ethyl acetate, to give 3-aryl (hetero) aniline.To a suspension of 2-bromopyridine (0.5 g, 3.2 mmol), 3-aminophenylboronic acid (0.49 g, 3.2 mmol), anhydrous K2CO3 (0.87 g, 6.3 mmol) and Pd(PPh3)4 (0.36 g, 0.32 mmol) in 1, 2-dimethoxyethane (50 mL) under argon, water (0.66 mL) is added. The mixture is heated under argon at 80 C. overnight. The reaction mixture is allowed to cool and water and EtOAc is added. The phases are separated in a funnel and the aqueous phase is reextracted with EtOAc. The combined organic phases are dried over Na2SO4 and the solvent Is evaporated. The crude product obtained is purified by chromatography on silica gel using hexane-EtOAc mixtures of increasing polarity as eluent, to afford the title compound.(b) In a manner similar to that of Example 7(b), the above nitro compound (0.92 g) gives Weigh 2-chloro-4-methylsulfonylbenzoic acid (165.5mg, 0.71mmol) and dissolve in DCM (10mL)Add 4 drops of DMF and heat to reflux. The solution gradually cleared and the endpoint of the reaction was monitored by TLC.After the reaction was completed, excess SOCl2 and DCM were removed by rotary evaporation and dissolved in anhydrous THF (10 mL).Take the 3- (2-pyridyl) aniline (100 mg, 0.59 mmol) prepared above and dissolve it in anhydrous THF (5 ml).TEA (164 muL, 1.18 mmol) was added and the ice-water bath was cooled to 0 C.The prepared anhydrous solution of 2-chloro-4-methylsulfonylbenzoyl chloride in THF was slowly added dropwise to the above solution, After the dropwise addition was completed, the temperature was slowly raised to room temperature for 5 hours, and the reaction endpoint was monitored by TLC. After the reaction was completed, the solution was in suspension.0.5 mL of distilled water was added and the solution gradually cleared. It was washed with saturated sodium carbonate solution (2 mL x 2) and the solution was separated.Take the organic phase slowly and add it to 50mL of distilled water. A white solid precipitates out and is filtered.Drying under vacuum gave 204.7 mg of a white solid with a yield of 90.1%.Weigh m-aminoacetophenone (100.0mg, 0.74mmol) in ethanol (3mL), Cu (OTf) 2 (26.8mg, 0.074mmol), TsOH · H2O (84.4mg, 0.44mmol), 1, 3-propanediamine (185muL, 2.22mmol) were added in this order, Ventilation and oxygen, heating to 80 C for 72h.After the reaction was completed, the reaction solution was cooled to room temperature, and concentrated by rotary evaporation. Ethyl acetate, water, and saturated sodium carbonate were added to make the mixture alkaline.Extract with ethyl acetate (25 mL x 3), wash with saturated brine (30 mL x 2), and dry over anhydrous sodium sulfate.Column chromatography (EA: PE 1: 3) yielded 62.3 mg of the product with a yield of 49.5%.Preparation follows the literature procedure described in J. Org. Chem. 2016, 81, 3256-3262. Equal amounts of compound 1 and 2 are added to a microwave vial (10 ml) equipped with a magnetic stirrer followed by a small addition of EtOH/H2O. The reaction is performed in a closed vial for half hour. After completion of the reaction, the mixture is concentrated under vacuum. The residue is purified by chromatography on reverse phase.

Molecular Weight:170.21
XLogP3:1.9
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:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes