2-Aminobenzimidazole → 4-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid (1H-benzoimidazol-2-yl)-amide

HRID 1592565Notes

Reaction equation

HRID 1592565 reaction equation
[NH2:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[C:11](N1C=CN=C1)(N1C=CN=C1)=[O:12].[CH3:23][C:24]1[C:25]([CH2:31][N:32]([CH2:39][C:40]2[C:45]([CH:46]([CH3:48])[CH3:47])=[CH:44][CH:43]=[CH:42][N:41]=2)[CH:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)=[N:26][CH:27]=[C:28]([CH3:30])[CH:29]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C>[NH:3]1[C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=[C:2]1[NH:1][C:11]([N:36]1[CH2:37][CH2:38][CH:33]([N:32]([CH2:31][C:25]2[C:24]([CH3:23])=[CH:29][C:28]([CH3:30])=[CH:27][N:26]=2)[CH2:39][C:40]2[C:45]([CH:46]([CH3:48])[CH3:47])=[CH:44][CH:43]=[CH:42][N:41]=2)[CH2:34][CH2:35]1)=[O:12]

Participants

7

Reactant 4

HCID 136242-AminobenzimidazoleHCID 682631,1'-CarbonyldiimidazoleHCID 516892Sodium BicarbonateHCID 58997074(3,5-Dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 589972194-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid (1H-benzoimidazol-2-yl)-amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-aminobenzimidazole (81 mg, 0.61 mmol) in CH2Cl2 (5 mL) and DMF (0.5 mL) was added 1,1′-carbonyldiimidazole (99 mg, 0.61 mmol) and the reaction stirred at reflux for 30 min. then at room temperature for 2 h after which a solution of (3,5-dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidine-4-yl-amine (109 mg, 0.31 mmol) in DMF (1 mL) was added and the reaction stirred at 65° C. overnight. The solution was cooled, treated with saturated aqueous NaHCO3 (25 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were washed with brine (1×30 mL), dried (Na2SO4), filtered, and concentrated. Purification of the crude material by radial chromatography on silica gel (1 mm plate, CH2Cl2/MeOH/NH4OH, 100:1:1 then 50:1:1 then 25:1:1) provided

Workup

  1. temperatureat reflux for 30 min.
  2. stirringthe reaction stirred at 65° C. overnight
  3. temperatureThe solution was cooled
  4. extractionextracted with CH2Cl2 (3×20 mL)
  5. washThe combined organic extracts were washed with brine (1×30 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude material by radial chromatography on silica gel (1 mm plate, CH2Cl2/MeOH/NH4OH, 100:1:1
  10. custom50:1:1 then 25:1:1) provided

Sources & evidence

ORD record
ord-21068b9845814a6fa6a97e82ff8db64b
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

Loading…