2-(4-aminophenyl)-2-methylpropanenitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-chloro-7-(3-chloropyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine (40 mg, 0.14 mmol), 2-(4-aminophenyl)-2-methylpropanenitrile (100 mg, 0.63 mmol) (prepared according to the reference: Axton, C. A. et al, J. Chem. Soc. Perkin Trans. 1, 1992, 2203.), and acetonitrile (0.5 mL) was heated in a sealed tube via microwave at 180° C. for 60 min. The solvent was removed in vacuo and the residue was purified by chromatography to give a light yellow solid (50 mg). prepared The solvent was removed in vacuo the residue was purified by chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-chloro-7-(3-chloropyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine (40 mg, 0.14 mmol), 2-(4-aminophenyl)-2-methylpropanenitrile (100 mg, 0.63 mmol) (prepared according to the reference: Axton, C. A. et al, J. Chem. Soc. Perkin Trans. 1, 1992, 2203.), and acetonitrile (0.5 mL) was heated in a sealed tube via microwave at 180° C. for 60 min. The solvent was removed in vacuo and the residue was purified by chromatography to give a light yellow solid (50 mg). prepared The solvent was removed in vacuo the residue was purified by chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 4,6-dichloro-1,5-naphthyridine-3-carboxylate (6.4 g, 23.6 mmol) and 2-(4-aminophenyl)-2-methylpropionitrile (5.6 g, 35 mmol) were dissolved in tert-butanol (200 mL), to the system added potassium carbonate (16.4 g, 119 mmol), and the reaction mixture was stirred under reflux for 2 h. After confirming a disappearance of the raw materials by a thin layer chromatography plate (ethyl acetate:petroleum ether=1:3), the reaction mixture was suction filtered, the filtrate was concentrated under reduced pressure, and the resulting residue was washed with diethyl ether to give 8.1 g of a pale yellow solid. under reflux for 2 h filtered the filtrate was concentrated under reduced pressure the resulting residue was washed with diethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Analogously to Example 25, 4-(1-cyano-1-methylethyl)-aniline is reacted with 4-methoxybenzoic acid chloride to give a yield of 85% of theory of the title compound in the form of beige crystals; m.p. 169°-171° C. A sample thereof is recrystallised from ethanol and then has a melting point of 172°-174° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A yellow suspension of 6-bromo-4-chloro-3-nitrocinnoline (1.75 g, 6.07 mmol), 2-(4-aminophenyl)-2-methylpropanenitrile (1.069 g, 6.67 mmol) and K2CO3 (1.677 g, 12.13 mmol) in MeCN (2 mL) was heated to reflux for 5 min. The workup followed general workup procedures, and the crude was purified on silica gel with PE/EtOAc as eluant to give 2-(4-(6-bromo-3-nitrocinnolin-4-ylamino)phenyl)-2-methylpropanenitrile as yellow solid (2.5 g, yield 100%). MS (m/z): 414 (M+H)+. was heated to reflux for 5 min the crude was purified on silica gel with PE/EtOAc as eluant

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 188 mg (1.16 mmol) 1,1′-Carbonyl-diimidazol (CDI) were given to a solution of 175 mg (1.09 mmol) 4-(cyano-dimethyl-methyl)-phenylamine (Hicks, T. A., J. Med. Chem. 22 (1979) 1460-1464) in 4.0 ml dichloro-methane and stirred for 12 h. A solution of 284 mg (1.09 mmol) 3-[4-(4-Amino-phenoxy)-pyrimidin-2-ylamino]-propan-1-ol in 6 ml dichloromethane was added within 30 min. and the mixture stirred for 12 h at r.t. The reaction mixture was evaporated and the residue was purified by chromatography on silica gel (ethyl acetate). The obtained material was left overnight with dichloromethane, the precipitate filtered, washed with ether and dried. Yield: 180 mg (37%) of the title compound. the mixture stirred for 12 h at r.t The reaction mixture was evaporated the residue was purified by chromatography on silica gel (ethyl acetate) The obtained material was left overnight with dichloromethane the precipitate filtered washed with ether dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Bromo-2,4-dichloropyrimidine (1.37 gm, 6 mmol), 2-(4-aminophenyl)-2-methylpropanenitrile (0.96 gm, 6 mmol) and diisopropyl ethylamine (1.6 mL, 9 mmol) were combined in 30 ml acetonitrile and stirred for 16 hr at RT. LC/MS at 16 hr indicated reaction was complete. Organics were washed sequentially with 1M citric acid solution, water, then brine. Organics were dried over sodium sulfate then decanted and evaporated to yield a crude material which was carried on as-is in the next step. (1.45 gm, 69%). MS m/z 353.3 (M+H) LC/MS at 16 hr indicated reaction Organics were washed sequentially with 1M citric acid solution, water Organics were dried over sodium sulfate then decanted evaporated