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With palladium on activated charcoal; hydrogen at 20℃; |
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With hydrogen In ethanol at 50℃; for 12h; |
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With hydrogen In tetrahydrofuran; methanol |
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With hydrogen In ethyl acetate for 48h; |
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With hydrogen In methanol; ethyl acetate at 20℃; for 16h; |
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With hydrogen In N,N-dimethyl-formamide at 20℃; for 12h; |
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With hydrogen In methanol at 20℃; for 3h; |
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With hydrogen In N,N-dimethyl-formamide at 20℃; for 18h; |
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With hydrogen In ethyl acetate at 20℃; |
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With hydrogen In methanol at 20℃; for 2h; |
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With hydrogen In ethyl acetate at 20℃; |
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With hydrogen In methanol at 20℃; |
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With hydrogen In ethyl acetate at 20℃; for 10h; |
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With hydrogen for 2h; |
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With hydrogen In ethyl acetate for 12h; |
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With sodium tetrahydroborate In methanol; ethyl acetate at 0℃; |
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With hydrogen In N,N-dimethyl-formamide for 1h; |
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With hydrogen |
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With hydrogen In methanol for 2h; |
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With hydrogen In methanol for 24h; atmospheric pressure; |
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With hydrogen In ethyl acetate for 4.5h; |
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With hydrogen In ethyl acetate for 16h; |
Methyl 1 -methyl-4-nitropyrrole-2- carboxylate 31 (6.0 g, 32.6 mmol) was dissolved in EtOAc (100 mL). A slurry of moist 10% Pd/C (600 mg) in EtOAc was added and the contents were stirred vigorously under H2 (70 psi) for 16 h. The reaction mixture was filtered through a bed of Celite. The Celite was washed with MeOH and the combined filtrate was evaporated under reduced pressure to furnish crude amine as dark oil. The crude oil, without any further purification, was taken up in CH3CN (60 mL). Contents were cooled to 0 °C and DIPEA (12 mL, 62.4 mmol) was added. A solution of l-methyl-2- trichloroacetylimidazole 24 (8.5 g, 31 mmol) in CH3CN (10 mL) was added and the reaction mixture was allowed to stir at ambient temperature for 14 h. Solvents were removed under reduced pressure and the solid obtained was washed with hexanes and filtered to afford 32. (8.0 g, 94 %). 1H-NMR (CDCl3) 09.08 (s, exch, IH, NH), 7.41 (s, IH, Py-C5H), 7.03 (s, IH, Im-C5H), 6.98 (s, IH, Im-C4H), 6.80 (s, IH, Py-C3H), 4.08 (s, 3H, CH3), 3.90 (s, 3H, CH3), 3.78 (s, 3H, OCH3). 13C-NMR (75 MHz, DMSO-d6) 6161.8 (+, s, CO), 157.1 (+, s, CO), 139.1 (+, s, Im-C2), 128.3 (-, d, Im- C4), 127.1 (-, d, Im-C5), 122.6 (+, s, Py-C2), 121.7 (-, d, Py-C5), 119.7 (+, s, Py-C4), 109.5 (-, d, Py-C3), 51.2 (-, q, OCH3), 37.9 (-, q, CH3), 35.5 (-, q, CH3). EI-HRMS: m/z calcd for C12H14N4O3 262.1066, found 262.1056 (M+, 100%), 174.0661 (20%), 109.0407 (40%). |
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With hydrogen In methanol; ethyl acetate for 14h; |
Methyl 4-nitro-pyrrole-2- carboxylate 31 (3.8 g, 20.6 mmol) was dissolved in a mixture of MeOH-EtOAc (1 : 1, 150 mL). A slurry of moist 10% Pd/C in EtOAc was added and the contents were stirred vigorously under hydrogen (70 psi) for 14 h. The reaction mixture was filtered through a bed of Celite. The Celite was washed with MeOH and the filtrate was concentrated under reduced pressure to furnish crude amine as oil. The crude amine without any further purification was taken up in CH3CN (150 mL) and DIEA (5 mL). A solution of l-methyl-4-nitro-2-trichloroacetylimidazole 25 (5.4 g, 19.8 mmol) in CH3CN (20 mL) was added and the reaction mixture was allowed to stir at ambient temperature for 14 h, during which solid precipitated out. The reaction mixture was filtered to furnish 34 as yellow solid (4.8 g, 70.5 %). 1H-NMR (CDCl3) 68.96 (s, exch, IH, NH), 7.82 (s, IH, Im-CH), 7.37 (d, IH, J = 1.9 Hz, Py-CH), 6.86 (d, IH, J = 1.9 Hz, Py-CH), 4.19 (s, 3H, CH3), 3.92 (s, 3H, CH3), 3.82 (s, 3H, CH3), 13C-NMR (75 MHz, DMSO-d6) 6160.9 (+, s, CO), 154.9 (+, s, CO), 144.5 (+, s, Im-C4), 137.8 (+, s, Im-C2), 126.9 (-, d, Im-C5), 121.9 (+, s, Py-C2), 121.6 (-, d, Py-C5), 119.1 (+, s, Py-C4), 109.3 (-, d, Py-C3), 51.2 (-, q, OCH3), 36.8 (-, q, CH3), 36.5 (-, q, CH3). EI- HRMS: m/z calcd for Ci2H13N5O5 307.0917; found 307.0920 (M+, 100%), 180.0538 (88%), 149.0358 (42%). |
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With sodium tetrahydroborate; 5%-palladium/activated carbon In methanol; water; ethyl acetate at 0℃; |
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With sodium tetrahydroborate; palladium 10% on activated carbon In methanol; water; ethyl acetate at 0 - 20℃; for 0.5h; |
MeO-Py-Ind (15)
A mixture of NaBH4 (92 mg, 2.44 mmol) in water (2ml) was added dropwise to a solution of MeO-Py-NO2 (9) (150 mg, 0.82 mmol) and Pd/C (10%) (30 mg) in EtOAc:MeOH (3:3) at 0 °C. The reaction mixture was allowed to warm up to rt and was stirred for 30 min. The catalyst was removed by vacuum filtration through Celite, and the solvent was evaporated to afford amine (14), which was used without further purification. A solution of 2-indole carboxylic acid (8) (120mg, 0.75mmol), PyBOP (429 mg, 0.83 mmol) and DIEA (261 ml, 1.5 mmol) in DCM (2 ml) was stirred at rt for 30 min. Next, a solution of amine (14) in DCM (2 ml) was added to the previous activated acid and was stirred at rt overnight. The reaction mixture was washed with HCl (1 M), extracted with DCM, washed with brine, dried over Na2SO4, then filtered and the solvent was evaporated in vacuo. A white solid was obtained in 90% yield. |
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With palladium 10% on activated carbon; hydrogen In methanol; water for 1h; Large scale; |
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With palladium 10% on activated carbon; hydrogen In methanol for 2h; Autoclave; |
Methyl 4-amino-1-methyl-1H-pyrrole-2-carboxylate (42)
182 mg (0.99 mmol) methyl 1-methyl-4-nitro-1H-pyrrole-2-carboxylate (41) was dissolved in 10 mL methanol in an autoclave. The solution was purged with Ar, then 10 mg 10 % Pd/C was added. The mixture was stirred vigorously under H2 (1 bar) for 2 h. Pd/C was removed by filtration, methanol was removed under reduced pressure. 430 mg (0.5 mmol, 99%) brownish oil was obtained. The amine was not stable so we used it without further purification. |
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With 5%-palladium/activated carbon; hydrogen In tetrahydrofuran for 2h; |
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