3-ethenylaniline

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: Treatment of 3-ethenylaniline (7 g) with diethylacetylene dicarboxylate (9.4 g), as described in Example 1b, gave ethyl 5-ethenyl-4-oxo-1,4-dihydroquinoline-2-carboxylate (0.16 g), mp 168°-170° C., δ (360 MHz, DMSO-d6) 1.37 (3H, t, CH3), 4.41 (2H, q, CH2), 5.25 and 5.55 (2H, 2dd, =CH2), 6.56 (1H, s, 3H), 7.38 (1H, d, 6-H), 7.62 (1H, t, 7-H), 7.90 (1H, d, 8-H), 8.15 (1H, 2d, CH=) and 11.87 (1H, bs, NH) and ethyl 7-ethenyl-4-oxo-1,4-dihydroquinoline-2-carboxylate (0.46 g), mp 177°-179° C., δ (360 MHz, DMSO-d6) 1.37 (3H, t, CH3),4.42 (2H, q, CH2), 5.47 and 5.99 (2H, 2d, =CH2), 6.65 (1H, bs, 3-H), 6.84 (1H, 2d, CH=), 7.54 (1H, d, 6-H) and 7.93 (1H, s, 8-H), 8.04 (1H, d, 5-H), 11.97 (1H, bs, NH).

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the above 3-ethenylnitrobenzene (10 g) in acetic acid (30 ml) was added zinc powder (10 g) and the mixture heated to 70° C. with stirring for two hours, then cooled to room temperature and filtered. Ethyl acetate (300 ml) was added to the filtrate, followed by 1M sodium hydroxide until pH 10. The organic layer was separated, washed with water (100 ml), brine (100 ml) and dried over magnesium sulphate. The solvent was removed under reduced pressure to give the crude product, which was purified by column chromatography to give 3-ethenylaniline (4.9 g), δ (60 MHz, CDCl3) 3.60 (2H, bs, NH2), 5.1, 5.2, 5.5 and 5.8 (3H, 4d, CH2 and CH) and 6.3 to 7.3 (4H, m, ArH). cooled to room temperature filtered Ethyl acetate (300 ml) was added to the filtrate The organic layer was separated washed with water (100 ml), brine (100 ml) dried over magnesium sulphate The solvent was removed under reduced pressure to give the crude product, which was purified by column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazole-2-carbaldehyde (4.00 g, 13.14 mmol) in 1,2-dichloroethane (240 mL) were added 3-vinylaniline (2.36 g, 19.71 mmol) and AcOH (0.79 g, 13.14 mmol), and the mixture was heated at 80° C. for 2 h. The reaction mixture was cooled to 0° C. and, to it, was added NaBH(OAc)3 (5.56 g, 26.20 mmol). The mixture was stirred at 40° C. overnight, and then the pH of the reaction mixture was adjusted to 7-8 at 0° C. with 10% K2CO3 solution. The reaction mixture was extracted with 5% MeOH in CHCl3 (2×200 mL), and the organic phase was dried over anhydrous Na2SO4, filtered, and evaporated to dryness under reduced pressure. The residue was purified by MPLC on silica gel using a mixture of MeOH and CH2Cl2 (1:19 (v/v)) as eluent to give the titled compound (2.89 g, 63%) as a solid. 1H NMR (400 MHz, CDCl3) δ 10.59 (br s, 1H), 8.94 (s, 1H), 8.37 (s, 1H), 7.81 (d, 1H, J=9.2 Hz), 7.77 (d, 1H, J=9.2 Hz), 7.45 (t, 1H, J=7.8 Hz), 7.20 (br d, 1H, overlapped, J=7.6 Hz), 7.15 (t, 1H, overlapped, J=7.8 Hz), 7.00 (d, 1H, J=8.0 Hz), 6.86 (d, 1H, J=7.6 Hz), 6.75 (t, 1H, J=2.0 Hz), 6.63 (dd, 1H, overlapped, J=17.6, 10.8 Hz), 6.61 (dd, 1H, overlapped, J=8.0, 2.0 Hz), 5.69 (dd, 1H, J=17.6, 0.8 Hz), 5.21 (dd, 1H, J=10.8, 0.8 Hz), 4.55 (s, 2H), 4.39 (br s, 1H), 2.51 (s, 3H); MS (ESI) m/z 408.21 (MH+). The reaction mixture was cooled to 0° C. and, to it The reaction mixture was extracted with 5% MeOH in CHCl3 (2×200 mL) the organic phase was dried over anhydrous Na2SO4 filtered evaporated to dryness under reduced pressure The residue was purified by MPLC on silica gel using a mixture of MeOH and CH2Cl2 (1:19 (v/v)) as eluent

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazole-2-carbaldehyde (4.00 g, 13.14 mmol) in 1,2-dichloroethane (240 mL) were added 3-vinylaniline (2.36 g, 19.71 mmol) and AcOH (0.79 g, 13.14 mmol), and the mixture was heated at 80° C. for 2 h. The reaction mixture was cooled to 0° C. and, to it, was added NaBH(OAc)3 (5.56 g, 26.20 mmol). The mixture was stirred at 40° C. overnight, and then the pH of the reaction mixture was adjusted to 7-8 at 0° C. with 10% K2CO3 solution. The reaction mixture was extracted with 5% MeOH in CHCl3 (2×200 mL), and the organic phase was dried over anhydrous Na2SO4, filtered, and evaporated to dryness under reduced pressure. The residue was purified by MPLC on silica gel using a mixture of MeOH and CH2Cl2 (1:19 (v/v)) as eluent to give the titled compound (2.89 g, 63%) as a solid. 1H NMR (400 MHz, CDCl3) δ 10.59 (br s, 1H), 8.94 (s, 1H), 8.37 (s, 1H), 7.81 (d, 1H, J=9.2 Hz), 7.77 (d, 1H, J=9.2 Hz), 7.45 (t, 1H, J=7.8 Hz), 7.20 (br d, 1H, overlapped, J=7.6 Hz), 7.15 (t, 1H, overlapped, J=7.8 Hz), 7.00 (d, 1H, J=8.0 Hz), 6.86 (d, 1H, J=7.6 Hz), 6.75 (t, 1H, J=2.0 Hz), 6.63 (dd, 1H, overlapped, J=17.6, 10.8 Hz), 6.61 (dd, 1H, overlapped, J=8.0, 2.0 Hz), 5.69 (dd, 1H, J=17.6, 0.8 Hz), 5.21 (dd, 1H, J=10.8, 0.8 Hz), 4.55 (s, 2H), 4.39 (br s, 1H), 2.51 (s, 3H); MS (ESI) m/z 408.21 (MH+). The reaction mixture was cooled to 0° C. and, to it The reaction mixture was extracted with 5% MeOH in CHCl3 (2×200 mL) the organic phase was dried over anhydrous Na2SO4 filtered evaporated to dryness under reduced pressure The residue was purified by MPLC on silica gel using a mixture of MeOH and CH2Cl2 (1:19 (v/v)) as eluent

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

Procedure: This compound was prepared according to the procedure of Example A1, step A, using 2,4-dichloro-5-methylpyrimidine and 3-vinylaniline as the starting materials in 39% yield. LCMS calculated for C13H13ClN3 (M+H)+: m/z=246.1. This compound was prepared

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

Procedure: This compound was prepared according to the procedure of Example A1, step A, using 2,4-dichloro-5-methylpyrimidine and 3-vinylaniline as the starting materials in 39% yield. LCMS calculated for C13H13ClN3 (M+H)+: m/z=246.1. This compound was prepared

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2,5-dichloro-N-(3-vinylphenyl)pyrimidin-4-amine trifluoroacetate (150 mg, 0.56 mmol) and 3-vinylaniline (200 mg, 1.0 mmol) in 2-methoxyethanol (3.8 mL) and 3 N hydrogen chloride in ethanol (0.56 mL) were mixed and heated to 150° C. for 30 minutes in a microwave. Purification by preparative LCMS (pH 2) gave the desired product as a trifluoroacetate salt (150 mg, 60%). LCMS for C20H17ClN4 (M+H)+: m/z=349.1. Purification by preparative LCMS (pH 2)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2,5-dichloro-N-(3-vinylphenyl)pyrimidin-4-amine trifluoroacetate (150 mg, 0.56 mmol) and 3-vinylaniline (200 mg, 1.0 mmol) in 2-methoxyethanol (3.8 mL) and 3 N hydrogen chloride in ethanol (0.56 mL) were mixed and heated to 150° C. for 30 minutes in a microwave. Purification by preparative LCMS (pH 2) gave the desired product as a trifluoroacetate salt (150 mg, 60%). LCMS for C20H17ClN4 (M+H)+: m/z=349.1. Purification by preparative LCMS (pH 2)

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

Procedure: Treatment of 3-ethenylaniline (7 g) with diethylacetylene dicarboxylate (9.4 g), as described in Example 1b, gave ethyl 5-ethenyl-4-oxo-1,4-dihydroquinoline-2-carboxylate (0.16 g), mp 168°-170° C., δ (360 MHz, DMSO-d6) 1.37 (3H, t, CH3), 4.41 (2H, q, CH2), 5.25 and 5.55 (2H, 2dd, =CH2), 6.56 (1H, s, 3H), 7.38 (1H, d, 6-H), 7.62 (1H, t, 7-H), 7.90 (1H, d, 8-H), 8.15 (1H, 2d, CH=) and 11.87 (1H, bs, NH) and ethyl 7-ethenyl-4-oxo-1,4-dihydroquinoline-2-carboxylate (0.46 g), mp 177°-179° C., δ (360 MHz, DMSO-d6) 1.37 (3H, t, CH3),4.42 (2H, q, CH2), 5.47 and 5.99 (2H, 2d, =CH2), 6.65 (1H, bs, 3-H), 6.84 (1H, 2d, CH=), 7.54 (1H, d, 6-H) and 7.93 (1H, s, 8-H), 8.04 (1H, d, 5-H), 11.97 (1H, bs, NH).