Potassium Carbonate → 10-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

HRID 1398794Notes

Reaction equation

HRID 1398794 reaction equation
[NH2:1][C:2]1[N:6]([CH2:7][CH2:8][CH2:9][CH2:10]O)[C:5]2[C:12]([CH:17]([CH2:20][CH3:21])[CH2:18][CH3:19])=[CH:13][CH:14]=[C:15]([Cl:16])[C:4]=2[N:3]=1.CS(Cl)(=O)=O.C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:16][C:15]1[C:4]2[N:3]=[C:2]3[NH:1][CH2:10][CH2:9][CH2:8][CH2:7][N:6]3[C:5]=2[C:12]([CH:17]([CH2:20][CH3:21])[CH2:18][CH3:19])=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 687615864-[2-Amino-4-chloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butan-1-ol

Product 1

HCID 13610182510-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazoleYield 47.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-[2-amino-4-chloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butan-1-ol (3.40 g, 10.8 mmol) in pyridine (50 mL) was added methanesulfonyl chloride (2.60 mL, 32.9 mmol) dropwise at 0° C. After stirring for 1 hr, aqueous sodium bicarbonate was added to the mixture, which was extracted with ethyl acetate. Organic layer was washed with 2N hydrochloric acid, water and brine, dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in N,N-dimethylformamide (100 mL) and potassium carbonate (4.50 g, 32.9 mmol) was added. The mixture was stirred at 110° C. for 15 hr. After cooling, the mixture was diluted with ethyl acetate, 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 30-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound (1.51 g, 5.17 mmol, 47%) as a pale yellow solid.

Workup

  1. extractionwas extracted with ethyl acetate
  2. washOrganic layer was washed with 2N hydrochloric acid, water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in N,N-dimethylformamide (100 mL)
  6. stirringThe mixture was stirred at 110° C. for 15 hr
  7. temperatureAfter cooling
  8. washwashed 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 30-100% ethyl acetate/n-hexane gradient mixture
  12. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-814cfa08eb6c41aa89fd66dd8e4558d5
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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