Methylamine → HCID 68319533, compound

HRID 1966763Notes

Reaction equation

HRID 1966763 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].[CH3:7][NH2:8].[Br:9][C:10]1[CH:32]=[CH:31][C:13]2[N:14]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:15]([C:17]3[CH:26]=[CH:25][CH:24]=[CH:23][C:18]=3[C:19]([NH:21]O)=[NH:20])=[N:16][C:12]=2[CH:11]=1>C1COCC1.N1C=CC=CC=1>[CH3:7][NH:8][C:2]([C:1]1[O:5][N:21]=[C:19]([C:18]2[CH:23]=[CH:24][CH:25]=[CH:26][C:17]=2[C:15]2[N:14]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:13]3[CH:31]=[CH:32][C:10]([Br:9])=[CH:11][C:12]=3[N:16]=2)[N:20]=1)=[O:3]

Participants

6

Reactant 3

HCID 6329MethylamineHCID 65578Oxalyl chlorideHCID 178448432HCID 178448432, compound

Product 1

HCID 68319533HCID 68319533, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of oxalyl chloride (0.17 mL, 1.99 mmol) in anhydrous THF (20 mL) is added methylamine 2.0M in THF (0.99 mL, 1.99 mmol) at 0° C. The solution is stirred at 0° C. to room temperature for 0.5 hours and added to a stirred solution of 2-(5-bromo-1-tert-butyl-1H-benzimidazol-2-yl)-N-hydroxy-benzamidine (350 mg, 0.9 mmol) in anhydrous pyridine (5 mL). The reaction mixture is stirred at room temperature for 1 hour and then heated to 50° C. and stirred for 16 hours. The reaction mixture is cooled to room temperature and concentrated in vacuo. Dichloromethane is added and the organics washed sequentially with saturated NaHCO3 (20 mL) solution and H2O (20 mL) then dried (Na2SO4), filtered and concentrated. Purification via flash chromatography (25 g silica gel, 50-60% EtOAc/heptane) affords 3-[2-(5-bromo-1-tert-butyl-1H-benzimidazol-2-yl)-phenyl]-[1,2,4]oxadiazole-5-carboxylic acid methylamide (150 mg, 37%)

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 1 hour
  2. stirringstirred for 16 hours
  3. temperatureThe reaction mixture is cooled to room temperature
  4. concentrationconcentrated in vacuo
  5. additionDichloromethane is added
  6. washthe organics washed sequentially with saturated NaHCO3 (20 mL) solution and H2O (20 mL)
  7. dry with materialthen dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification via flash chromatography (25 g silica gel, 50-60% EtOAc/heptane)

Sources & evidence

ORD record
ord-cb84843541094ddea8f9a82bf5e7003a
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

Loading…