4-Amino-3-methylbenzonitrile

Light yellow powder

To a stirring 100 mL solution of THF at room temperature, added 9.89 g (61 mmol, 1 eq) of the benzonitrile. Then added 1 g palladium over 10percent carbon. Then added 25 mL of methanol. The system was then put under 50 psi of pressure in a hydrogenator. After no more hydrogen consumption was observed, the reaction was stopped and filtered over celite. Performed column chromatography using 1:1 hexane:dichloromethane as the mobile phase. Obtained 7.5 g of a beige powder. Yield was 93percent. 4-Cyano-2-methylaniline was synthesized as previously described (J. Med. Chem. (1991), 34, 3295): To a solution of 3-methyl-4-nitrobenzonitrile (2.0 g, 12.34 mmol) in acetic acid (20 L) was added dropwise a solution of SnCl2 (9.6 g, 49.38 mmol) in conc. HCl (20 mL). After stirring for 3 h, the mixture was added carefully to a saturated NH4OH solution (120 mL) at 0° C. The resulting mixture was extracted with EtOAc (4.x.30 mL). The combined organic layers were sequentially washed with H2O (30 mL) and a saturated NaCl solution (30 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (10percent EtOAc/hex) to give 4-cyano-2-methylaniline as a white solid (1.48 g, 92percent): TLC (30percent EtOAc in hexane) Rf0.23. This material was used without further purification4-Amino-3-methyl-benzonitrile: To a solution of 3-methyl-4-nitro-benzonitrile (20 g, 0.123 mol) in HOAc (200 mL) was added iron powder (17.55 g, 0.309 mol). After 10 min, the reaction was exothermic and turned to dark color. The reaction mixture was allowed to stir at room temperature for 14 h and then diluted with EtOAc (200 mL). The brown precipitate was filtered through a pad of celite and the filtercake was rinsed with EtOAc. The filtrate was concentrated in vacuo and the residue was purified by flash chromatography (40percent EtOAc/hexane) to yield the title compound (15.3 g, 92percent). To a solution of 3-methyl-4-nitro-benzonitrile (20 g, 0.123 mol) in HOAc (200 mL) was added iron powder (17.55 g, 0.309 mol). After 10 min, the reaction was exothermic and turned to dark color. The reaction mixture was allowed to stir at room temperature for 14 h and then diluted with EtOAc (200 mL). The brown precipitate was filtered through a pad of celite and the filtercake was rinsed with EtOAc. The filtrate was concentrated in vacuo and the residue was purified by flash chromatography (40percent EtOAc/hexane) to yield the title compound (15.3 g, 92percent). 1H NMR (300 MHz, CDCl3) δ 7.30-7.34 (2H, m), 6.64 (1H, d, J=8.7 Hz), 2.16 (3H, s). LCMS (M+H)+ m/z 133 (t=0.93 min).C. General procedure: 12 mL of 3 m/L HCl was added to a solution of compound 3 (1.1 g, 5.7 mmol) in 30 mL methanol, the reaction was heated and refluxed for 8 h. When the reaction was completed, concentrated, added some water, and basified the mixture with NaHCO4-iodo-2-methylaniline (2000mg, 8.58mmol) and cyanide(1.15g, 12.87mmol, 1.5eq)were added to pyridine. A reaction mixture was heated to 150~160 °C and stirred for 12hrs. A reaction mixture was diluted with methylene chloride. A diluted solution was washed with copper sulfate for several times. A mixture was washed with HExample 8: N-{4-[3-(4-tert-Butyl-benzyl)-ureidomethyl]-2-methyl-6-vinyl-phenyl}-methanesulfonamide; EPO

Molecular Weight:132.16
XLogP3:1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:132.068748264
Monoisotopic Mass:132.068748264
Topological Polar Surface Area:49.8
Heavy Atom Count:10
Complexity:156
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes