4-methyl-3-(trifluoromethyl)aniline

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: Using 5-methylsalicylic acid and 4-methyl-3-(trifluoromethyl)aniline as the raw materials, the same operation as the example 16 gave the title compound.

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

Procedure: Using 5-chlorosalicylic acid and 4-methyl-3-(trifluoromethyl)aniline as the raw materials, the same operation as the example 16 gave the title compound.

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

Procedure: In a like manner to the preparation of 2-chloro-N4-(3,4-ethylenedioxyphenyl)-5-fluoro-4-pyrimidineamine, 2,4-dichloro-5-fluoropyrimidine and 4-methyl-3-trifluoromethylaniline were reacted to provide 2-chloro-5-fluoro-N4-(4-methyl-3-trifluoromethylphenyl)-4-pyrimidineamine. 1H NMR (CDCl3): δ 8.10 (d, 1H, J=3.0 Hz), 7.85-7.78 (m, 2H), 7.33 (d, 1H, J=9.3 Hz), 6.96 (bs, 1H), 2.48 (d, 3H, J=1.2 Hz); 19F NMR (282 MHz, CDCl3): −17641, −44541; LCMS: purity: 97%; MS (m/e): 306 (MH+). were reacted

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

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

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a dried vessel, 68 mg (0.388 mMol) 5-amino-2-methylbenzotrifluoride are dissolved in 7 ml toluene and cooled in an ice bath. Then 580 μl Me3Al (2 M in toluene; 1.16 mMol) are added via syringe. After 1 h at rt, a solution of 126 mg (0.388 mMol) 6-(6-methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid methyl ester in 1.5 ml THF is added and the solution is stirred for ½ h in an oil bath of 110° C. The solution is cooled in an ice bath and hydrolyzed with 13 ml of a sat. NH4Cl solution. After 15 min stirring, the mixture is diluted with EtOAc and water, the aq. phase separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Chromatography (Combi Flash; CH2Cl2/acetone 99:1→19:1) and crystallization from DIPE/hexane gives the title compound: m.p.: 188° C.; Anal.: C, H, N, F; MS: [M+1]+=468; TLC (CH2Cl2/acetone 9:1): Rf=0.32; 1H-NMR (DMSO-d6): δ ppm 10.85 (s, HN), 8.69 (s, 1H), 8.28 (d, 1H), 8.24 (s, 1H), 8.10 (d, 1H), 7.93 (d, 1H), 7.90 (s, 1H), 7.80 (d, 1H), 7.66 (t, 1H), 7.48 (d, 1H), 7.44 (d, 1H), 7.07 (s, 1H), 4.50 (s, H2C), 3.4 (s, H3C), 2.43 (s, H3C). cooled in an ice bath After 15 min stirring the aq. phase separated off extracted twice with EtOAc The organic layers are washed with water and brine dried (Na2SO4) concentrated Chromatography (Combi Flash; CH2Cl2/acetone 99:1→19:1) and crystallization from DIPE/hexane

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

Procedure: The title compound was synthesized according to the procedure described for the preparation of Example 231 using 6 (50 mg, 0.22 mmol) and 4-methyl-3-trifluoromethyl-phenylamine (0.03 mL, 0.33 mmol) to provide 236 (14 mg, 17% yield) as a brown solid. LC-MS (M+H=370, obsd.=370). 1H NMR (400 MHz, d6-DMSO): δ 11.73 (s, 1H), 9.11 (s, 1H), 8.52 (dd, 1H), 8.47 (dd, 1H), 8.18 (d, 1H), 7.90 (d, 1H), 7.54 (dd, 1H), 7.43 (m, 2H), 7.28 (m, 2H), 2.41 (s, 3). The title compound was synthesized