M-AMINOBENZYLCYANIDE

General procedure: To a solution of 2 (150.1 mg, 0.66 mmol) and NHA. A nanoporous metal cesium catalyst (3.2 mg, 0.03 mmol) Ethylene glycol dimethyl ether (3 mL) and 3-nitrophenylacetonitrile (48.65mg, 0.3mmol) was added to the Reaction kettle, hydrogen (16 bar) was introduced, heated and stirred, the reaction temperature was controlled at 100 ° C, Reaction time control at 35h, column chromatography (baby gel, 200-300 mesh; Developing solvent, petroleum ether: ethyl acetate = 10: 1) to give 35.7 mg of 3-aminophenylacetonitrile in 90percent yield.To a stirred solution of NHIron powder (517 mg, 9.27 mmol) was added to a solution of 3-nitrophenylacetonitrile (500 mg, 3.09 mmol) in acetic acid (9.5 ml) and water (6.6 ml). The reaction was stirred at 40 To a solution of 3-nitro-phenyl-acetonitrile (3.20 g, 19.7 mmol) in MeOH(50 mL) was added Pd/C (10percent wt, -50percent H(c) 5-Phenyl-furan-2-carboxylic acid [3-(lH-tetrazol-5- ylmethyl)-phenyl]-amide (75); (i) (3-Amino-phenyl)-acetonitrile (80); A solution of 3-nitrophenyl acetonitrile (500 mg, 3.1 mmol) in 5percent AcOH (10 ml) was heated to 80°C. Iron powder (1.5 g, 27 mmol) was then added and the resulting mixture stirred for 2 h. The reaction mixture was filtered through celite and the filter cake washed with MeCN (4 x 50 ml). The combined MeCN layers were evaporated in vacuo and the residue was re-dissolved in EtOAc (30 ml) followed by 2M HC1 (30 ml). The aqueous layer was separated, basified to pH 10 with 6M NaOH, and extracted with EtOAc (3 x 80 ml). The combined organic layers were dried (MgSO4), filtered and the solvent removed in vacuo to give the title compound. Yield: 140 mg, 34percent ; 1H NMR (400 MHz, CDC13) : 5 3.65 (s, 2H), 3.75 (s, 2H), 6.60-6. 70 (m, 3H), 7.15 (t, 1H)A mixture of nitrobenzene acetic acid (1 g, 5.52 mmoles), 1.66 mL OF SOC12, 10 mL dry CHC13 was refluxed for 14 hours. CHC13 and excess thionyl chlorid were removed in vacuo, and the residue was evaporated twice with 25 mL of toluene to remove traces of thionyl chlorid. The residue was taken into 10 mL of toluene and 30 mL of cold concentrated ammonium hydroxyde were added. The white solid formed was collected and dried with etanol in vacuo. Yield: 79 percent. 'H NMR (DMSO-d6, 300MHZ) 8 : 8.14 (M, 2H), 7.71 (M, 2H), 7.06 (brs, 2H), 3.58 (s, 2H). 2- (3-NITROPHENYL) acetamide was added with 10 mL of POC13 and the mixture was heated at reflux for 2 hours. After cooling, the mixture was poured into ice, basified with NA2CO3 and extracted with CH2C12. The organic layer was dried over NA2S04, filtered and evaporated. Purified by flash chromatography on silica gel CH2C12. Yield : 41percent H NMR (CDC13, 300 MHz) 5 : 8. 14 (M, 2H), 7.69 (d, 1H, J = 8HZ), 7.56 (M, 1H), 3.88 (s, 2H). A solution of 15 mL HBr 48percent was cooled to 0°C. (430 mg, 2.65 mmoles) OF 3-NITROBENZONITRILE, (574 mg, 4. 85 mmoles) of Sn were added successively. The mixture was stirred at room temperature for 3 hours, then poured into ice. The solution was basified with NA2C03, extracted with CH2C12, dried, filtered and evaporated. Purified by flash chromatography on silica gel ETOH/CH2CL2 (2: 98). Yield: 32percent H NMR (DMSO-d6, 300MHZ) 8 : 7.37 (M, 2H), 6.81 (M, 2H), 3.86 (s, 2H). 3-AMINOBENZONITRILE was then reacted with 2-chloroethylisocyanate as described in examples 1- 12 to obtain desired product. Purified by flash CHRMATOGRAPHY on silica gel ETOH/CH2CL2 (5: 95). Yield: 78percent H NMR (CDCL3, 300 MHz) 8 : 8.12 (brs, NH, 1H), 7.26 (M, Ar, 4H), 6.97 (brs, NH, 1H), 3.63 (m, CH2, 6H).A mixture of nitrobenzene acetic acid (1 g, 5.52 mmoles), 1.66 mL OF SOC12, 10 mL dry CHC13 was refluxed for 14 hours. CHC13 and excess thionyl chlorid were removed in vacuo, and the residue was evaporated twice with 25 ML of toluene to remove traces of thionyl chlorid. The residue was taken into 10 mL of toluene and 30 ML of cold concentrated ammonium hydroxyde were added. The white solid formed was collected and dried with etanol in vacuo. Yield: 79 percent. 1H NMR (DMSO-d6, 300MHZ) 8 : 8.14 (M, 2H), 7.71 (M, 2H), 7.06 (brs, 2H), 3.58 (s, 2H). 2- (3-NITROPHENYL) ACETAMIDE was added with 10 mL of POC13 and the mixture was heated at reflux for 2 hours. After cooling, the mixture was poured into ice, basified with NA2C03 and extracted with CH2C12. The organic layer was dried over NA2S04, filtered and evaporated. Purified by flash chromatography on silica gel CH2C12. Yield: 41percent 1H NMR (CDC13, 300 MHz) 8 : 8.14 (M, 2H), 7.69 (d, 1H, J = 8HZ), 7.56 (m, 1H), 3.88 (s, 2H). A solution of 15 mL HBr 48percent was cooled to 0°C. (430 mg, 2.65 mmoles) of 3-nitrobenzonitrile, (574 mg, 4.85 mmoles) of Sn were added successively. The mixture was stirred at room temperature for 3 hours, then poured into ice. The solution was basified with NA2CO3, extracted with CH2CK, dried, filtered and evaporated. Purified by flash chromatography on silica gel ETOH/CH2CL2 (2: 98). Yield: 32percent 1H NMR (DMSO-D6, 300MHZ) B : 7.37 (M, 2H), 6.81 (M, 2H), 3. 86 (s, 2H). 3-AMINOBENZONITRILE was then reacted with 2-chloroethylisocyanate as described in examples 1- 12 to obtain desired product. Purified by flash chrmatography on silica gel ETOH/CH2C12 (5: 95). Yield: 78percentEXAMPLE 367 Preparation of Compound 544 in Table 18 An analogous reaction to that described in example 363 but starting with To a stirred solution of tert-butyl 2-formyl-6-azaspiro[3.4]octane-6-carboxylate (CAS: 203662-55-9) (225 mg, 1.0 mmol) and 2-(3-aminopheny])acetonitrile (CAS: 4623-249) (136 mg, 1.03 mmol) in MeOH (10 mL) at room temperature was added decaborane (43 mg, 0.35 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated. The residue was purified bysilica gel chromatography eluted with PE/EtOAc(3/1, v/v) to afford intermediate 119 (340 mg, 99% yield) as a yellow solid.To a stirred solution oftert-butyl 6-oxo-2-azaspiro[3.4]octane-2-carboxylate (CAS: 1363382-39-1) (225 mg, 1.0 mmol) and

Molecular Weight:132.16
XLogP3:0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:132.068748264
Monoisotopic Mass:132.068748264
Topological Polar Surface Area:49.8
Heavy Atom Count:10
Complexity:145
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes