{3-[3-(2-cyano-benzyl)-5-ethyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]-cyclohexyl}-carbamic acid benzyl ester → 2-[2-(3-Amino-cyclohexyl)-5-ethyl-4-oxo-4,5-dihydro-imidazo[4,5-c]pyridin-3-ylmethyl]-benzonitrile

HRID 2244809Notes

Reaction equation

HRID 2244809 reaction equation
C(OC(=O)[NH:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[N:28]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[C:36]#[N:37])[C:20]3[C:21](=[O:27])[N:22]([CH2:25][CH3:26])[CH:23]=[CH:24][C:19]=3[N:18]=2)[CH2:12]1)C1C=CC=CC=1>[Pd].CCO.C1COCC1>[NH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[N:28]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[C:36]#[N:37])[C:20]3[C:21](=[O:27])[N:22]([CH2:25][CH3:26])[CH:23]=[CH:24][C:19]=3[N:18]=2)[CH2:12]1

Participants

4

Reactant 1

HCID 58788436{3-[3-(2-cyano-benzyl)-5-ethyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]-cyclohexyl}-carbamic acid benzyl ester

Product 1

HCID 587884392-[2-(3-Amino-cyclohexyl)-5-ethyl-4-oxo-4,5-dihydro-imidazo[4,5-c]pyridin-3-ylmethyl]-benzonitrileYield 82%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

A solution of {3-[3-(2-cyano-benzyl)-5-ethyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]-cyclohexyl}-carbamic acid benzyl ester (66 mg, 0.13 mmol) in 1:3 EtOH/THF (8 mL) was hydrogenated over 10% Pd/C (70 mg, 0.065 mmol) at room temperature. After 2 h, the catalyst was removed by filtration, rinsing with MeOH, and the filtrate was concentrated in vacuo. The crude product was purified by flash chromatography, eluting with 90:10:0.5 CH2Cl2/MeOH/NH4OH to give 2-[2-(3-amino-cyclohexyl)-5-ethyl-4-oxo-4,5-dihydro-imidazo[4,5-c]pyridin-3-ylmethyl]-benzonitrile (40 mg, 82% yield). The HCl salt was prepared by treating the amine in EtOAc with ethereal HCl (0.2 mL). 1H-NMR (CDCl3): δ 7.72 (dd, 1H, J=7.6, 1.2 Hz), 7.50 (t, 1H, J=7.6 Hz), 7.39 (t, 1H, J=7.6 Hz), 7.14 (d, 1H, J=7.2 Hz), 6.93 (d, 1H, J=7.6 Hz), 6.72 (dd, 1H, J=7.6, 2.0 Hz), 6.07 (m, 2H), 4.07 (m, 2H), 2.70 (m, 2H), 1.92 (m, 1H), 1.83 (m, 2H), 1.60 (m, 4H), 1.40 (m, 2H), 1.37 (dt, 3H, J=7.2, 3.2 Hz). MS: calculated for C22H25N5O+H 376.2; found: 376.2.

Workup

  1. customthe catalyst was removed by filtration
  2. washrinsing with MeOH
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe crude product was purified by flash chromatography
  5. washeluting with 90:10:0.5 CH2Cl2/MeOH/NH4OH

Sources & evidence

ORD record
ord-33fbe2151b634dd1a120d04968e1d585
Source dataset
uspto-grants-2010_03
Patent number
US07678909B1

Reaction notes

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