2-(4-AMINOPHENYL)-2-METHYLPROPANENITRILE

light yellow crystalline

which is subsequently reduced to the amine 2-3.10556] The above reaction scheme illustrates the synthesis of a compound of the invention 2-13. Methylation of starting material 2-1 yields compound 2-2, which is subsequently reduced to the amine 2-3. In a separate reaction, compound 2-4 is converted to a salt, such as an HC1 salt, which is then reacted, for example, with 2-nitrovinyl-hydroxylamine to yield compound 2-6. Further cyclization yields compound 2-7. Halogenation with a reagent such as POd3 results in compound 2-8, which can be coupled with intermediate 2-3 to yield 2-9. The nitro moiety of 2-9 is subsequently reduced to an amine, and a further reaction with 4-nitrophenyl carbonochloridate results in the heterocycle 2-11. The desired compound 2-13 is then prepared by coupling to the benzoxazolyl boronate 2-12, for example in a Suzuki coupling.To a suspension of 4-nitrophenylacetonitrile 1 (1.0 equiv, 4.50 g, 27.8 mmol), tetrabutyl ammonium bromide (TBAB, 0.448 g, 1.39 mmol, 0.05 equiv) and iodomethane (11.8 g, 83.4 mmol, 3.0 equiv) in dichloromethane (DCM, 40.0 mL) was added sodium hydroxide (2.78 g, 69.5 mmol, 2.5 equiv) in water (40.0 mL) dropwise. A solution of 9.4 g (0.35 mol) of iron powder, 37.2 g (0.694 mol) of ammonium chloride solution (37.2 g of ammonium chloride / 40 ml of water) was added successively to 22 g (0.115 mol) of intermediate 4 dissolved in 300 ml of absolute ethanol, 120 ° C reflux reaction 6h, The organic layer was dried over anhydrous magnesium sulfate, filtered, and the filtrate was dried by filtration. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate / petroleum ether = 1 : LO, V: V), was light yellow oily liquid intermediates 5 17.23g, yield 93 , 2-methyl-2-(4-nitro-phenyl)-propionitrile was dissolved in ethyl acetate (20ml) and treated with stannous chloride dihydrate (3.52g, 15.86mmol). After stirring overnight at room temperature, the reaction mixture was basified with aqueous sodium carbonate. The organic layer was separated, washed with water, dried and concentrated to oil. The crude compound was purified by column chromatography over silica gel using ethyl acetate/pet ether (1:9) as eluent to give 2-(4-aminophenyl)-2-methyl propionitrile (0.45g, 89percent) as oil.10percent Pd/C (300 mg) was added to a solution of 2-methyl-2-(4-nitro-phenyl)- propionitrile (3.00 g; 15.8 mmol), prepared as in l(A), in MeOH (65 mL). The mixture was hydrogenated at 1 bar at room temperature for 2.5 hours, the catalyst was filtered off and the filtrate was concentrated under reduced pressure to give the title compound as a yellow oil (2.40 g; 80percent yield).LCMS (RT): 0.78 min (Method A); MS (ES+) gave m/z: 161.1 (MH+).2-Methyl-2-(4-nitrophenyl)propanenitrile (Compound of step 1, 16 g, 84.1 mmol) and Raney- Ni (4.16 g) were shaken in THF-MeOH [(1:1), 160 mL] under 40 psi of hydrogen for 10 hours at RT, After completion of reaction, the catalyst was filtered-off and the solvent was evaporated to dryness. The crude product was purified by column chromatography (silica gel, ethyl acetate in hexane) to obtain the title compound as oil.Yield: 10 g (74 percent); Step 2:2-methyl-2-(4-nitrophenyl) propanenitrile (4.5 g, 23.6 mmol) was added to a reaction vessel, to which were successively added Pd/C (450 mg) and 50 mL ethyl acetate. The system was vacuumed and hydrogen was introduced. The resulting mixture is reacted at room temperature for 15 hrs. The resulting reaction was filtered with Celite, and washed with ethyl acetate. The resulting filtrate was concentrated to obtain a colorless oil of 2-(4-aminophenyl)-2-methyl propanenitrile (3.5 g).10208] 2-methyl-2-(4-nitrophenyl) propanenitrile (4.5 g, 23.6 mmol) was added to a reaction vessel, to which were successively added Pd/C (450 mg) and 50 mE ethyl acetate. The system was vacuumed and hydrogen was introduced. The resulting mixture is reacted at room temperature for 15 hrs. The resulting reaction was filtered with Celite, and washed with ethyl acetate. The resulting filtrate was concentrated to obtain a colorless oil of 2-(4-aminophenyl)-2-methyl propanenitrile (3.5 g).To a stirred solution of

Molecular Weight:160.22
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:160.100048391
Monoisotopic Mass:160.100048391
Topological Polar Surface Area:49.8
Heavy Atom Count:12
Complexity:191
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes