4-bromo-3-chlorobenzaldehyde

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

Procedure: Starting from 4-Bromo-3-chloro-benzaldehyde, the title compound was prepared by the method described for (4-Bromo-benzyl)-(2,2-dimethoxy-ethyl)-amine (1). Rt=0.94 min (Method C). Detected mass: 308.3/310.3 (M+H+).

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

Procedure: Starting from 4-Bromo-3-chloro-benzaldehyde, the title compound was prepared by the method described for (4-Bromo-benzyl)-(2,2-dimethoxy-ethyl)-amine (1). Rt=0.94 min (Method C). Detected mass: 308.3/310.3 (M+H+).

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

Procedure: 5-Amino-1-methyl-1,2-dihydropyrazol-3-one (0.08 g, 0.75 mmol), 3-chloro-4-bromobenzaldehyde (0.13 g, 0.75 mmol) from Example 40C, and 4,4dimethyl-1,3-cyclohexanedione (0.10 g, 0.75 mmol) were processed as described in Example 22 to provide the title compound (0.22 g, 67%). 1H NMR (DMSO-d6) δ 0.92 (s, 3H), 0.98 (s, 3H), 1.78 (t, 2H), 2.55 (m, 2H), 3.47 (s, 3H), 4.81 (s, 1H), 7.0 (dd, 1H), 7.29 (d, 1H), 7.55 (d, 1H), 9.52 (bs, 1H), 9.67 (s, 1H); MS (ESI−) m/z 436 (M−H)−; Anal. Calcd for C19H19N3BrClO2: C, 52.23; H, 4.35; N, 9.62. Found: C, 52.35;H, 4.24; N, 9.62.

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

Procedure: 5-Amino-1-methyl-1,2-dihydropyrazol-3-one (0.84 g, 0.75 mmol), 4bromo-3-chlorobenzaldehyde (0.157 g, 0.75 mmol) from Example 40C, and 1,3-cyclopentanedione (0.074 g, 0.75 mmol) was processed as described in Example 1 to provide 0.20 g of the title compound. 1H NMR (DMSO-d6) δ 2.29 (t, 2H), 2.68 (m, 2H), 3.49 (s, 3H), 4.69 (s, 1H), 7.02 (dd, 1H), 7.33 (d, 1H), 7.6 (d, 1H), 9.55 (s, 1H), 10.41 (s, 1H); MS (ESI−) m/z 394 (M−H)−; Anal. Calcd for C16H13N3BrClO2: C, 48.66;H, 3.29; N, 10.64. Found: C, 48.92;H, 3.13; N, 10.72.

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

Procedure: 2H-Pyran-3,5(4H,6H)-dione (0.057 g, 05 mmol), 3-chloro4-bromo-benzaldehyde (0.11 g, 0.5 mmol), and 5-amino-1-methyl-1,2-dihydropyrazol-3-one (0.056g, 0.5 mmol) were processed as described in Example 26C to provide 0.145 g of the title compound. 1H NMR (300 MHz, DMSO-d6) δ 3.5 (s, 3H), 4.0 (s, 2H), 4.52 (q, 2H), 4.92 (s, 1H), 7.03 (dt, 1H), 7.32(t, 1H), 7.6 (dd, 1H), 9.62 (s, 1H), 10.1 (s, 1H); MS (ESI−) m/z 410 (M−H:) Anal. calcd for C16H13N3BrClO3: C, 46.80;H,3.19; N, 10.23. Found: C, 46.77;H, 3.43; N, 10.27.

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

Procedure: 5-Amino-1-methyl-1,2-dihydropyrazol-3-one (0.08 g, 0.75 mmol), 3-chloro-4-bromobenzaldehyde (0.13 g, 0.75 mmol) from Example 40C, and 4,4-dimethyl-1,3-cyclohexanedione (0.10 g, 0.75 mmol) were processed as described in Example 22 to provide the title compound (0.22 g, 67%). 1H NMR (DMSO-d6) δ 0.92 (s, 3H), 0.98 (s, 3H), 1.78 (t, 2H), 2.55 (m, 2H), 3.47 (s, 3H), 4.81 (s, 1H), 7.0 (dd, 1H), 7.29 (d, 1H), 7.55 (d, 1H), 9.52 (bs, 1H), 9.67 (s, 1H); MS (ESI−) m/z 436 (M−H)−; Anal. Calcd for C19H19N3BrClO2: C, 52.23; H, 4.35; N, 9.62. Found: C, 52.35; H, 4.24; N, 9.62.

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

Procedure: 5-Amino-1-methyl-1,2-dihydropyrazol-3-one (0.84 g, 0.75 mmol), 4-bromo-3-chlorobenzaldehyde (0.157 g, 0.75 mmol) from Example 40C, and 1,3-cyclopentanedione (0.074 g, 0.75 mmol) was processed as described in Example I to provide 0.20 g of the title compound. 1H NMR (DMSO-d6) δ 2.29 (t, 2H), 2.68 (m, 2H), 3.49 (s, 3H), 4.69 (s, 1H), 7.02 (dd, 1H), 7.33 (d, 1H), 7.6 (d, 1H), 9.55 (s, 1H), 10.41 (s,1H); MS (ESI−) m/z 394 (M−H)−;

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

Procedure: 2H-Pyran-3,5(4H,6H)-dione (0.057 g, 05 mmol), 3-chloro-4-bromo-benzaldehyde (0.11 g, 0.5 mmol), and 5-amino-1-methyl-1,2-dihydropyrazol-3-one (0.056 g, 0.5 mmol) were processed as described in Example 26C to provide 0.145 g of the title compound. 1H NMR (300 MHz, DMSO-d6) δ 3.5 (s, 3H), 4.0 (s, 2H), 4.52 (q, 2H), 4.92 (s, 1H), 7.03 (dt, 1H), 7.32(t, 1H), 7.6 (dd, 1H), 9.62 (s, 1H), 10.1 (s, 1H); MS (ESI−) m/z 410 (M−H)−; Anal. calcd for C16H13N3BrClO3: C, 46.80; H,3.19; N, 10.23. Found: C, 46.77; H, 3.43; N, 10.27

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methylmagnesium bromide (4.8 mL, 3M, 14.4 mmol) was added dropwise to the solution of 4-bromo-3-chlorobenzaldehyde (1.52 g, 7.0 mmol) in tetrahydrofuran at −40° C. Then the mixture was stirred at 25° C. for 3 hrs. Saturated ammonium chloride solution (10 mL) was added to the mixture. The mixture was concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ethe/ethyl acetate=1:1) to give 1-(4-bromo-3-chlorophenyl)ethanol as a white solid (1.32 g, 81%). 1H NMR (300 MHz, d6-DMSO): 7.69 (d, J=8.1, 1H), δ 7.53 (d, J=0.9, 1H), 7.19 (dd, J1=8.1, 1H J2=0.9, 1H), 5.38 (d, J=3.6, 1H), δ 4.70 (m, 1H), 1.30 (d, J=6.6, 3H). The mixture was concentrated to give a residue The residue was purified by column chromatography (silica gel, petroleum ethe/ethyl acetate=1:1)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (4-bromo-3-chlorophenyl)methanol (2.0 g, 9.0 mmol), pyridinium chlorochromate (2912 mg, 13.5 mmol) in dichloromethane (50 mL0 was stirred at 25° C. for 3 hours. The mixture was concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ethe/ethyl acetate=1:1) to give 4-bromo-3-chlorobenzaldehyde as a white solid (1.6 g g, 81%). 1H NMR (300 MHz, d6-DMSO): δ 9.96 (s, 1H), 7.69 (d, J=8.1, 1H), δ 7.53 (d, J=0.9, 1H), 7.19 (dd, J=8.1, 1H J2=0.9, 1H) The mixture was concentrated to give a residue The residue was purified by column chromatography (silica gel, petroleum ethe/ethyl acetate=1:1)

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

Procedure: Starting from 4-Bromo-3-chloro-benzaldehyde, the title compound was prepared by the method described for (4-Bromo-benzyl)-(2,2-dimethoxy-ethyl)-amine (1). Rt=0.94 min (Method C). Detected mass: 308.3/310.3 (M+H+).