methyl piperazine-2-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Carbomethoxypiperazine was treated with benzyl chloroformate (1.0 eq) in aqueous NaHCO3 to give 1-benzyloxycarbonyl-3-carbomethoxypiperazine. This material was treated with di-tert-butyldicarbonate (1.1 eq) and triethylamine (1.0 eq) in THF to produce 1-tert-butyoxycarbonyl-4-benzyloxycarbonyl-2-carbomethoxypiperazine. Hydrogenation of this compound in methanol using 10% Pd—C gives the title compound after filtration and solvent removal.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound was synthesized from methyl piperazine-2-carboxylate and 6-chloronicotinonitrile as described for example 39 step 1 (90 mg, yield 35%). 1H NMR (400 MHz, MeOD) δ 8.42 (dd, J=2.4 Hz, 0.6 Hz, 1H), 7.76 (dd, J=9.0 Hz, 2.3 Hz, 1H), 6.90 (m, 1H), 4.39-4.35 (dd, J=13.2 Hz, 2.6 Hz, 1H), 3.95-3.90 (m, 1H), 3.76 (s, 3H), 3.63-3.60 (dd, J=8.4 Hz, 3.4 Hz, 1H), 3.52-3.47 (dd, J=13.1 Hz, 8.4 Hz, 1H), 3.45-3.39 (ddd, J=13.1 Hz, 9.3 Hz, 3.4 Hz, 1H), 3.13-3.08 (m, 1H), 2.86-2.79 (ddd, J=12.5 Hz, 9.1 Hz, 3.5 Hz, 1H).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: piperazine-2-carboxylic acid dihydrochloride (750 mg, 3.7 mmol) was suspended in MeOH (15 mL) and sodium bicarbonate (620 mg, 7.4 mmol) was added and stirred for 4 h. The reaction mixture was diluted with CH2Cl2 (15 mL) and cooled to 0° C. (Trimethylsilyl)diazomethane (15 mL, 2M in hexane) was added dropwise until the yellow color persisted. The solution was stirred at room temperature for 3 h and concentrated under reduced pressure. The crude product was purified by column chromatography (neutral alumina, eluent 5-6% MeOH in CHCl3) to get methyl piperazine-2-carboxylate (150 g, yield 28%). 1H NMR (300 MHz, CDCl3) δ 3.74 (s, 3H), 3.51-3.47 (dd, J=8.0 Hz, 3.4 Hz, 1H), 3.24-3.19 (dd, J=12.1 Hz, 3.3 Hz, 1H), 3.04-2.99 (m, 1H), 2.96-2.86 (m, 3H), 2.83-2.77 (m, 1H) was added dropwise until the yellow color The solution was stirred at room temperature for 3 h concentrated under reduced pressure The crude product was purified by column chromatography (neutral alumina, eluent 5-6% MeOH in CHCl3)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-1-phenyl-1H-indole-3-carboxaldehyde is reacted with piperazine-2-carboxylic acid methyl ester as described in Example 1 to afford 4-(3-formyl-1-phenyl-1H-indole-2-yl)-piperazine-2-carboxylic acid methyl ester (9% yield) as a yellow solid. LC/MS: MS 364 (M+H); RT 2.54 min; NMR (CDCl3): 10.29 (1H, s), 8.26 (1H, d), 7.07-7.65 (m, buried), 6.98 (1H, d), 3.60-4.10 (4H, m), 2.60-3.55 (6H, m).

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Carbomethoxypiperazine was treated with benzyl chloroformate (1.0 eq) in aqueous NaHCO3 to give 1-benzyloxycarbonyl-3-carbomethoxypiperazine. This material was treated with di-tert-butyldicarbonate (1.1 eq) and triethylamine (1.0 eq) in THF to produce 1-tert-butoxycarbonyl-4-benzyloxycarbonyl-2-carbomethoxypiperazine. Hydrogenation of this compound in methanol using 10% Pd—C gave the title compound after filtration and solvent removal.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-1-phenyl-1H-indole-3-carboxaldehyde is reacted with piperazine-2-carboxylic acid methyl ester as described in Example 1 to afford 4-(3-formyl-1-phenyl-1H-indole-2-yl)-piperazine-2-carboxylic acid methyl ester (9% yield) as a yellow solid. LC/MS: MS 364 (M+H); RT 2.54 min; NMR (CDCl3): 10.29 (1H, s), 8.26 (1H, d), 7.07-7.65 (m, buried), 6.98 (1H, d), 3.60-4.10 (4H, m), 2.60-3.55 (6H, m).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Carbomethoxypiperazine was treated with benzyl chloroformate (1.0 eq) in aqueous NaHCO3 to give 1-benzyloxycarbonyl-3-carbomethoxypiperazine. This material was treated with di-tert-butyldicarbonate (1.1 eq) and triethylamine (1.0 eq) in THF to produce 1-tert-butyoxycarbonyl-4-benzyloxycarbonyl-2-carbomethoxypiperazine. Hydrogenation of this compound in methanol using 10% Pd—C gives the title compound after filtration and solvent removal.