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

HRID 2244802Notes

Reaction equation

HRID 2244802 reaction equation
C(OC(=O)[NH:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[N:33]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[C:41]#[N:42])[C:20]3[C:21](=[O:32])[N:22]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[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:33]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[C:41]#[N:42])[C:20]3[C:21](=[O:32])[N:22]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:23]=[CH:24][C:19]=3[N:18]=2)[CH2:12]1

Participants

4

Reactant 1

HCID 58788445{3-[5-benzyl-3-(2-cyano-benzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]-cyclohexyl}-carbamic acid benzyl ester

Product 1

HCID 587884492-[2-(3-Amino-cyclohexyl)-5-benzyl-4-oxo-4,5-dihydro-imidazo[4,5-c]pyridin-3-ylmethyl]-benzonitrileYield 75%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

A solution of {3-[5-benzyl-3-(2-cyano-benzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]-cyclohexyl}-carbamic acid benzyl ester (78 mg, 0.14 mmol) in 1:3 EtOH/THF (8 mL) was hydrogenated over 10% Pd/C (73 mg, 0.068 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 94:6:0.5 CH2Cl2/MeOH/NH4OH to give 2-[2-(3-amino-cyclohexyl)-5-benzyl-4-oxo-4,5-dihydro-imidazo[4,5-c]pyridin-3-ylmethyl]-benzonitrile (45 mg, 75% yield). The HCl salt was prepared by treating the amine in EtOAc with ethereal HCl (0.2 mL). 1H-NMR (500 MHz, 1 mL CDCl3+1 δL d-Trifluoroacetic acid: 6 (dd, 1H, J=7.8, 1.4 Hz), 7.62 (dt, 1H, J=7.8, 1.4 Hz), 7.53 (dt, 1H, J=7.8, 1.4 Hz), 7.49 (d, 1H, J=7.5 Hz), 7.37 (br m, 5H), 7.26 (dd, 1H, J=7.8, 1.4 Hz), 6.60 (d, 1H, J=7.5 Hz), 6.35 (d, 1H, J=16.3 Hz), 6.17 (d, 1H, J=16.3 Hz), 5.28 (d, 1H, J=14.0 Hz), 5.25 (d, 1H, J=14.0 Hz), 3.45 (br s, 1H), 3.34 (br t, 1H, J=11.7 Hz), 2.38 (br d, 1H, J=11.7 Hz), 2.29 (q, 1H, J=11.7 Hz), 2.15 (br d, 1H, J=11.7 Hz), 2.0 (br d, 1H, J=13.3 Hz), 1.66 (m, 2H), 1.59 (q, 1H, J=11.7 Hz), 1.48 (br t, 1H, J=11.7 Hz). MS: calculated for C27H27N5O+H 438.2; found: 438.3.

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 94:6:0.5 CH2Cl2/MeOH/NH4OH

Sources & evidence

ORD record
ord-96a8dc53a5ae4cd88e9c54a5dc207bac
Source dataset
uspto-grants-2010_03
Patent number
US07678909B1

Reaction notes

Loading…