3-methyl-4-phenoxyaniline

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:

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

Procedure: The nitro compound prepared above was reduced under H2 using 10% Pd/C catalyst in MeOH to give 3-methyl-4-phenoxyaniline. 1H NMR (CDCl3) δ 7.27 (m, 2H), 6.97 (m, 1H), 6.83 (m, 2H), 6.80 (d, 1H), 6.60 (d, 1H), 6.52 (m, 1H), 3.53 (br s, 2H), 2.11 (s, 3H). MS (DCl/NH3) m/e 200 (M+H)+, 217 (M+H+NH3)+.

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 4-chloro-6-iodo-quinazoline (5.0 g, 17.2 mmol) and the 3-methyl-4-phenoxyaniline (17.2 mmol) were mixed together in 1:1 dichloroethane and t-butanol (50 ml). The reaction mixture was heated at 90° C. for 4 hours whereupon a yellow precipitate was observed. The reaction was cooled down and the precipitate was collected and afforded (6-iodoquinazolin-4-yl)-(3-methyl-4-phenoxy-phenyl)-amine. (8.0 g, 94%). M/z, 454. 1H NMR (CD3OD): δ: 9.12(s, 1H), 8.83(s, 1H), 8.39(d, 1H, J=8.8 Hz), 7.63(d, 1H, J=8.8 Hz), 7.55 (d, 1H, J=2.1 Hz), 7.35(dd,1H, J1=J2=8.5 Hz), 7.28(t, 2H, J=8.1 Hz,), 7.05 (t, J=8.5 Hz), 6.87(d, 1H, J=8.1 Hz), 3.81(s, 3H). The reaction was cooled down the precipitate was collected

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

Procedure: To a stirred solution of 3-methyl-4-phenoxynitrobenzene (2) (548 g, 2.39 moles, 1.0 eq.) in methanol (5 L) was added 10% Pd/C (100 g, 50% wet, 46.98 mmol, 0.02 eq.). Then the reaction mixture was stirred under a hydrogen atmosphere (60-80 psi) for 15-16 hours at room temperature in a 2 gallon Parr hydrogenator. The progress of the reaction was monitored by TLC (50% ethyl acetate in hexanes, sm Rf=0.69, pr Rf=0.47, UV visible). Then the reaction mixture was filtered through Celite, and the solid was washed with excess methanol. The filtrate was concentrated under reduced pressure to give 3-methyl-4-phenoxyaniline as a pale brown viscous liquid (451.0 9, 95%). The 3-methyl-4-phenoxyaniline was found to be pure by 1H and 13C NMR spectra, and used as such in the next reaction. Then the reaction mixture was filtered through Celite the solid was washed with excess methanol The filtrate was concentrated under reduced pressure

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

Procedure: 2-Methyl-4-nitro-1-phenoxybenzene and 10% Pd/C (3.35 g) were dissolved in 200 mL EtOH and stirred under 1 atmosphere of H2 overnight. The reaction mixture was filtered through Celite with the aid of 50 mL EtOH and concentrated to provide 3-methyl-4-phenoxybenzenamine as an oil, which was used in Step C without further purification. The reaction mixture was filtered through Celite with the aid of 50 mL EtOH concentrated

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 4-chloro-6-iodo-quinazoline (5.0 g, 17.2 mmol) and the 3-methyl-4-phenoxyaniline (17.2 mmol) were mixed together in 1:1 dichloroethane and t-butanol (50 ml). The reaction mixture was heated at 90° C. for 4 hours whereupon a yellow precipitate was observed. The reaction was cooled down and the precipitate was collected and afforded (6-iodo-quinazolin-4-yl)-(3-methyl-4-phenoxy-phenyl)-amine. (8.0 g, 94%). M/z, 454. 1H NMR (CD3OD): δ: 9.12(s, 1H), 8.83(s, 1H), 8.39 (d, 1H, J=8.8 Hz), 7.63(d, 1H, J=8.8 Hz), 7.55 (d, 1H, J=2.1 Hz), 7.35(dd,1H, J1=J2=8.5 Hz), 7.28(t, 2H, J=8.1 Hz, ), 7.05 (t, J=8.5 Hz), 6.87(d, 1H, J=8.1 Hz), 3.81 (s, 3H). The reaction was cooled down the precipitate was collected

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

Procedure: To a stirred solution of 3-methyl-4-phenoxynitrobenzene (2) (548 g, 2.39 moles, 1.0 eq.) in methanol (5 L) was added 10% Pd/C (100 g, 50% wet, 46.98 mmol, 0.02 eq.). Then the reaction mixture was stirred under a hydrogen atmosphere (60-80 psi) for 15-16 hours at room temperature in a 2 gallon Parr hydrogenator. The progress of the reaction was monitored by TLC (50% ethyl acetate in hexanes, sm Rf=0.69, pr Rf=0.47, UV visible). Then the reaction mixture was filtered through Celite, and the solid was washed with excess methanol. The filtrate was concentrated under reduced pressure to give 3-methyl-4-phenoxyaniline as a pale brown viscous liquid (451.0 g, 95%). The 3-methyl-4-phenoxyaniline was found to be pure by 1H and 13C NMR spectra, and used as such in the next reaction Then the reaction mixture was filtered through Celite the solid was washed with excess methanol The filtrate was concentrated under reduced pressure