4-{(5,6,7,8-Tetrahydro-quinolin-8-yl)-[1-(2-trimethylsilanyl-ethoxymethyl)-1h-benzoimidazol-2-ylmethyl]-amino}-butyronitrile → N1-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-Benzimidazol-2-ylmethyl)-N1-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine

HRID 1624230Notes

Reaction equation

HRID 1624230 reaction equation
[N:1]1[C:10]2[CH:9]([N:11]([CH2:17][C:18]3[N:22]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:21]4[CH:31]=[CH:32][CH:33]=[CH:34][C:20]=4[N:19]=3)[CH2:12][CH2:13][CH2:14][C:15]#[N:16])[CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1>N.[Ni].CO>[N:1]1[C:10]2[CH:9]([N:11]([CH2:17][C:18]3[N:22]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:29])([CH3:28])[CH3:30])[C:21]4[CH:31]=[CH:32][CH:33]=[CH:34][C:20]=4[N:19]=3)[CH2:12][CH2:13][CH2:14][CH2:15][NH2:16])[CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 1

HCID 691784354-{(5,6,7,8-Tetrahydro-quinolin-8-yl)-[1-(2-trimethylsilanyl-ethoxymethyl)-1h-benzoimidazol-2-ylmethyl]-amino}-butyronitrile

Product 1

HCID 59694106N1-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-Benzimidazol-2-ylmethyl)-N1-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamineYield 66.7%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 222AmmoniaSolventHCID 887MethanolSolvent

Procedure

4-{(5,6,7,8-Tetrahydro-quinolin-8-yl)-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-ylmethyl]-amino}-butyronitrile (840 mg, 1.75 mmol) was dissolved in NH3 saturated MeOH (15 mL), treated with Raney nickel (excess), and placed under 45 psi H2 on a Parr shaker for 16 hours. The mixture was diluted with MeOH and filtered through Celite. The cake was washed with MeOH and the combined filtrate was concentrated under reduced pressure. Purification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 50:2:1) afforded the desired amine (560 mg, 66%) as an orange syrup. 1H NMR (CDCl3) δ −0.10 (s, 9H), 0.81 (t, 2H, J=9.0 Hz), 1.43-1.50 (m, 4H), 1.59-1.76 (m, 1H), 1.86-2.09 (m, 2H), 2.08-2.23 (m, 1H), 2.56-2.71 (m, 4H), 2.76-2.85 (m, 2H), 2.41 (t, 2H, J=8.1 Hz), 4.07-4.12 (m, 3H), 5.71 (d, 1H, J=11.1 Hz), 7.37 (d, 1H, J=11.1 Hz), 7.05 (dd, 1H, J=7.5, 4.5 Hz), 7.21-7.29 (m, 2H), 7.34 (d, 1H, J=6.6 Hz), 7.40-7.45 (m, 1H), 7.71-7.76 (m, 1H), 8.58 (d, 1H, J=3.6 Hz).

Workup

  1. filtrationfiltered through Celite
  2. washThe cake was washed with MeOH
  3. concentrationthe combined filtrate was concentrated under reduced pressure
  4. customPurification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 50:2:1)

Sources & evidence

ORD record
ord-e70e03a2826345d3b9996ebfb1815ab8
Source dataset
uspto-grants-2014_07
Patent number
US08778967B2

Reaction notes

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