Reaktion #9052

Reaktionsgleichung

2-{[(2-cyano-4-methoxycarbonyl-benzyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester

ammonia

→

amide

Ausbeute 36.0%

4-{[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-methyl}-3-cyano-benzamide

Ausbeute 36.0%

Lösungsmittel

water

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe mixture was filtered through a celite pad
2. 2
   Einengenthe filtrate concentrated under reduced pressure
3. 3
   SonstigeThe crude residue was purified by column chromatography (88:12 CH2Cl2:MeOH)
4. 4
   Sonstigeto afford

Vorschrift

To 0.5 mL of Raney Nickel in water was added a solution of 2-{[(2-cyano-4-methoxycarbonyl-benzyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester (0.55 g, 1 mmol) in methanol (25 mL). The solution was then saturated with ammonia gas for 10 minutes. The reaction vessel was then shaken vigorously under an atmosphere of hydrogen (40 psi) for 16 hours. The mixture was filtered through a celite pad and the filtrate concentrated under reduced pressure. The crude residue was purified by column chromatography (88:12 CH2Cl2:MeOH) to afford to give the amide (0.20 g, 36%). 1H NMR (CDCl3) δ 1.73 (m, 1H), 2.01 (m, 2H), 2.35 (m, 1H), 2.85 (m, 2H), 3.88 (t, 2H, J=15.9 Hz), 4.16 (m, 1H), 4.21 (d, 1H, J=9.6 Hz), 4.26 (d, 1H, J=7.8 Hz), 5.71 (br, 1H, NH), 6.12 (br, 1H, NH), 7.19 (m, 3H), 7.46 (d, 1H, J=7.8 Hz), 7.55 (br, 2H), 7.80 (d, 1H, J=8.1 Hz), 7.87 (d, 1H, J=8.1 Hz), 7.96 (s, 1H), 8.64 (dd, 1H, J=4.5 Hz). 13C NMR (CDCl3) δ 21.71, 24.65, 29.44, 49.92, 53.09, 61.84, 112.81, 117.49, 122.30 (4C), 122.97, 130.44 (2C), 131.98, 132.32, 133.56, 135.37, 138.05 (2C), 147.13, 147.29, 155.27, 156.87, 167.82. ES-MS m/z 437 (M+H). Anal. Calcd. for C26H24N6O.0.6CH2Cl2: C, 65.54; H, 5.21; N, 17.24. Found: C, 65.93; H, 5.51; N, 17.44.

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