Potassium Carbonate → 5-[8-Chloro-5-(1-ethylpropyl)-2-methyl-2,3-dihydro-1H-imidazo[1,2-a]benzimidazol-1-yl]-N,N,4-trimethylpyridin-2-amine

HRID 1628663Notes

Reaction equation

HRID 1628663 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][C:12]3[CH:13]=[N:14][C:15]([N:19]([CH3:21])[CH3:20])=[CH:16][C:17]=3[CH3:18])[N:7]([CH2:22][CH:23](O)[CH3:24])[C:6]=2[C:5]([CH:26]([CH2:29][CH3:30])[CH2:27][CH3:28])=[CH:4][CH:3]=1.CS(Cl)(=O)=O.C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1.O>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:12]4[C:17]([CH3:18])=[CH:16][C:15]([N:19]([CH3:21])[CH3:20])=[N:14][CH:13]=4)[CH:23]([CH3:24])[CH2:22][N:7]3[C:6]=2[C:5]([CH:26]([CH2:29][CH3:30])[CH2:27][CH3:28])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 687657431-[4-Chloro-2-{[6-(dimethylamino)-4-methylpyridin-3-yl]amino}-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]propan-2-ol

Product 1

HCID 577861755-[8-Chloro-5-(1-ethylpropyl)-2-methyl-2,3-dihydro-1H-imidazo[1,2-a]benzimidazol-1-yl]-N,N,4-trimethylpyridin-2-amineYield 69%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

To a solution of 1-[4-chloro-2-{[6-(dimethylamino)-4-methylpyridin-3-yl]amino}-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]propan-2-ol (Reference Example 94; 23 mg, 0.053 mmol) in pyridine (0.50 mL) was added methanesulfonyl chloride (0.012 mL, 0.160 mmol) dropwise at 0° C. The mixture was warmed to room temperature and stirred for 5 hr. Aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. Organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting crude mesylate was dissolved in 1-methyl-2-pyrrolidinone (1.0 mL) and potassium carbonate (22 mg, 0.159 mmol) was added. The mixture was stirred at 50° C. for 4 hr. Water was added and the mixture was extracted with ethyl acetate. Organic layer was washed with water and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound (15 mg, 0.036 mmol, 69%) as a colorless solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washOrganic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resulting crude mesylate was dissolved in 1-methyl-2-pyrrolidinone (1.0 mL)
  6. stirringThe mixture was stirred at 50° C. for 4 hr
  7. extractionthe mixture was extracted with ethyl acetate
  8. washOrganic layer was washed with water and brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture
  12. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-6371be9dd1174ceebe3a90c3c72f99fb
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

Loading…