2-(2,6-dichlorophenyl)acetonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,6-dichloro-phenyl-acetonitrile (15.0 g, 80.62 mmol) in the dichloromethane (50 mL) and H2SO4 (40 mL) is added (slowly) a mixture of H2SO4 (14 mL) and HNO3 (5.5 mL) at 0° C. The reaction mixture is stirred at 0° C. for 20 minutes, warned to room temperature for half hour, and then concentrated to remove organic solvent. The solution is poured into a beaker containing ice-water (400 mL) to give a crystalline precipitate, which is collected by vacuum filtration and washed with water to afford the product (20.44 g, 82.4%). warned to room temperature for half hour concentrated to remove organic solvent The solution is poured into a beaker containing ice-water (400 mL) to give a crystalline precipitate, which is collected by vacuum filtration washed with water

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,6-dichloro-phenyl-acetonitrile (15.0 g, 80.62 mmol) in the dichloromethane (50 mL) and H2SO4 (40 mL) is added (slowly) a mixture of H2SO4 (14 mL) and HNO3 (5.5 mL) at 0° C. The reaction mixture is stirred at 0° C. for 20 minutes, warned to room temperature for half hour, and then concentrated to remove organic solvent. The solution is poured into a beaker containing ice-water (400 mL) to give a crystalline precipitate, which is collected by vacuum filtration and washed with water to afford the product (20.44 g, 82.4%). warned to room temperature for half hour concentrated to remove organic solvent The solution is poured into a beaker containing ice-water (400 mL) to give a crystalline precipitate, which is collected by vacuum filtration washed with water

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound was prepared in an analogous manner to the compound of Example 2 from 2,6-dichlorophenylacetonitrile (Aldrich), 204°-207° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound was prepared in an analogous manner to the compound of Example 2 from 2,6-dichlorophenylacetonitrile (Aldrich), mp. 204°-207° C.

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diisopropylamine (19.2 mL, 0.135 mol) in THF (75 mL) was added dropwise at room temperature to n-BuLi in hexane (67.5 mL, 0.135 mol) under argon atmosphere. The mixture was stirred for 0.5 h and then brought to -78° C.C. A solution of 2,6-dichlorophenyl acetonitrile (25 g, 0.135 mol) in THF (50 mL) was added dropwise while the reaction mixture was maintained at -78° C.C. The resulting mixture was stirred for 1 h, whereafter a solution of ethyl-3-bromoproionate (17.2 mL, 0.135 mol) in THF (50 mL) was added dropwise. The resulting mixture was stirred for 1 h, and then allowed to reach room temperature. After an additional 1 h at 25° C.C., the mixture was quenched with 10% aqueous hydrochloride solution. The phases were separated and the aqueous phase was extracted with diethyl ether (3×75 mL). The combined organic phases were dried (MgSO4), filtered, and concen-trated in vacuo affording ethyl-4-cyano-4-(2,6-dichlorophenyl)-butanoate (37 g) as an oil. A solution of the butanoate (3.53 g, 15 mmol) in HCl-saturated ethanol (100 mL) was hydrogenated at 50 psi over PtO2 (0.9 g) in a Parr apparatus. Removal of the catalyst by filtration, followed by evaporation of the EtOH, yielded an oily residue. The oil was taken up in 15% NaOH and was extracted with diethylether (3×30 mL), dried, filtered, and concentrated in vacuo. The oily residue was purified by flash chromatography using CH2Cl2 /MeOH (19/1) as eluent, affording pure racemic-69 (0.9 g, 85%): MS m/e 244.95 (M+ +1, 15.1), 243.95 (M+, 3.5), 242.95 (M+ -1, 24.1), 208.00 (19.3), 179.00 (29.3), 173.9 (61.3), 171.9 (100), 137.00 (31.6), 115.00 (20.5) brought to -78° C was added dropwise The resulting mixture was stirred for 1 h to reach room temperature After an additional 1 h at 25° C , the mixture was quenched with 10% aqueous hydrochloride solution The phases were separated the aqueous phase was extracted with diethyl ether (3×75 mL) The combined organic phases were dried (MgSO4) filtered

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound was prepared in an analogous manner to the compound of Example 2 from 2,6-dichlorophenylacetonitrile (Aldrich), mp. 204°-207° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound was prepared in an analogous manner to the compound of Example 2 from 2,6-dichlorophenylacetonitrile (Aldrich), mp. 204°-207° C.

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Aminonicotinaldehyde (100 mg, 0.78 millimole (hereinafter “mmol”)), 2,6-dichlorophenylacetonitrile (217 mg, 1.2 mmol), 10% aqueous NaOH (0.101 mL, 0.25 mmol) and 700 uL of absolute ethanol are combined and heated at 65° C. for 24 hours (hereinafter “h”). The reaction mixture is cooled to ambient temperature and the solvents are evaporated under reduced pressure. The residue is diluted with 700 uL of DMSO filtered and purified with preparative reverse phase chromatography to afford the title compound as a yellow solid (191 mg, 84% yield). MS ES+ m/z=290. The reaction mixture is cooled to ambient temperature the solvents are evaporated under reduced pressure The residue is diluted with 700 uL of DMSO filtered purified with preparative reverse phase chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound was prepared in an analogous manner to the compound of Example 2 from 2,6-dichlorophenylacetonitrile (Aldrich), mp. 204°-207° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound was prepared in an analogous manner to the compound of Example 2 from 2,6-dichlorophenylacetonitrile (Aldrich), mp. 204°-207° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5.25 parts of (2,6-dichlorophenyl)methanone, 4.08 parts of intermediate 8 and 105 parts of acetic acid was stirred for 2 hours at room temperature. There were added 1.96 parts of potassium cyanide and stirring was continued for 20 hours. The reaction mixture was poured into water and the product was extracted with dichloromethane. The extract was washed with NaOH (10%) and water, dried, filtered and evaporated. The residue was purified by column chromatography (silica gel; CH2Cl2 /hexane 80:20). The eluent of the desired fraction was evaporated and the residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried, yielding 4.28 parts (49.3%) of (±)-α-[2-acetyl-5-ethylphenyl)amino]-2,6-dichlorobenzeneacetonitrile; mp. 111.3° C. (interm. 9). stirring was continued for 20 hours the product was extracted with dichloromethane The extract was washed with NaOH (10%) and water dried filtered evaporated The residue was purified by column chromatography (silica gel; CH2Cl2 /hexane 80:20) The eluent of the desired fraction was evaporated the residue was crystallized from 2,2'-oxybispropane The product was filtered off dried