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

HRID 8956Notes

Reaction equation

HRID 8956 reaction equation
C(OC([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[CH2:17][N:18]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([O:38]C)=O)=[CH:32][C:31]=1[C:40]#[N:41])[CH:19]1[C:28]2[N:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:22][CH2:21][CH2:20]1)=O)(C)(C)C.[NH3:42]>[Ni].O.CO>[NH:10]1[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:8]=[C:9]1[CH2:17][N:18]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([NH2:42])=[O:38])=[CH:32][C:31]=1[C:40]#[N:41])[CH:19]1[C:28]2[N:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:22][CH2:21][CH2:20]1

Participants

6

Reactant 2

HCID 222AmmoniaHCID 68617128HCID 68617128, compound

Product 1

HCID 219850754-{[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-methyl}-3-cyano-benzamideYield 36%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

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.

Workup

  1. filtrationThe mixture was filtered through a celite pad
  2. concentrationthe filtrate concentrated under reduced pressure
  3. customThe crude residue was purified by column chromatography (88:12 CH2Cl2:MeOH)
  4. customto afford

Sources & evidence

ORD record
ord-e8c191f4c49e4165b58ee9f2d4333e3c
Source dataset
uspto-grants-2006_08
Patent number
US07091217B2

Reaction notes

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