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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 899727
Notes
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Reaction equation

HRID 899727 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
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 222AmmoniaSolvent
HCID 887
Methanol
Solvent

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-1cf7848bee5e4a8aab7c74637ba5f54a
Source dataset
uspto-grants-2008_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07354934B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes