Methanol → 1-(cyclopropylmethyl)-2-[(5-ethoxy-2-pyridinyl)methyl]-1H-benzimidazole-5-carbonitrile

HRID 1796483Notes

Reaction equation

HRID 1796483 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14]#[N:15])=[CH:13][C:8]=3[N:7]=[C:6]2[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][N:18]=2)[CH2:3][CH2:2]1.CO[Na].CO.[CH2:29](I)[CH3:30]>CS(C)=O.O>[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14]#[N:15])=[CH:13][C:8]=3[N:7]=[C:6]2[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:29][CH3:30])=[CH:19][N:18]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 887MethanolHCID 6340IodoethaneHCID 221812711-(cyclopropylmethyl)-2-[(5-hydroxy-2-pyridinyl)methyl]-1H-benzimidazole-5-carbonitrileHCID 178418582HCID 178418582, compound

Product 1

HCID 221812731-(cyclopropylmethyl)-2-[(5-ethoxy-2-pyridinyl)methyl]-1H-benzimidazole-5-carbonitrileYield 64.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of 1-(cyclopropylmethyl)-2-[(5-hydroxy-2-pyridinyl)methyl]-1H-benzimidazole-5-carbonitrile (120 mg, 0.394 mmol) in DMSO (1 mL) was added MeONa (25% in MeOH, 0.47 mmol). After being stirred at room temperature for 30 min, MeOH was removed in vacuo and EtI (0.47 mmol) was added, and the resulting mixture was stirred at room temperature overnight. The solution was diluted with H2O (10 mL), extracted with EtOAc (2×20 mL), washed with H2O (2×10 mL), and lastly dried over MgSO4. The residue obtained after evaporation was purified by silica gel column chromatography to give the pure product as an oil (84 mg, 64%). 1H NMR (400 MHz, CDCl3): δ 8.19 (d, J=3.0 Hz, 1H), 8.04 (s, 1H), 7.49 (d, J=8.4 Hz, 1H), 7.42 (d, J=8.4 Hz, 1H), 7.24 (d, J=8.8 Hz, 1H), 7.13 (dd, J=10.0 Hz, J=2.8 Hz, 1H), 4.47 (s, 2H), 4.15 (d, J=6.8 Hz, 2H), 4.04 (q, J=7.0 Hz, 2H), 1.41 (t, J=7.0 Hz, 3H), 1.14–1.08 (m, 1H), 0.60–0.54 (m, 2H), 0.36–0.30 (m, 2H). MS (ES) (M+H)+=333.

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. extractionextracted with EtOAc (2×20 mL)
  4. washwashed with H2O (2×10 mL)
  5. dry with materiallastly dried over MgSO4
  6. customThe residue obtained
  7. customafter evaporation
  8. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d67c2d6bab5c4f0a9b0b876c537611dc
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

Loading…