Potassium Carbonate → 10-Chloro-7-(1-ethylpropyl)-1-(6-methoxy-4-methylpyridin-3-yl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

HRID 1628627Notes

Reaction equation

HRID 1628627 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]([O:19][CH3:20])=[CH:16][C:17]=3[CH3:18])[N:7]([CH2:21][CH2:22][CH2:23][CH2:24]O)[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[CH:13]=[N:14][C:15]([O:19][CH3:20])=[CH:16][C:17]=4[CH3:18])[CH2:24][CH2:23][CH2:22][CH2:21][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 687647414-{4-Chloro-7-(1-ethylpropyl)-2-[(6-methoxy-4-methylpyridin-3-yl)amino]-1H-benzimidazol-1-yl}butan-1-ol

Product 1

HCID 5778634910-Chloro-7-(1-ethylpropyl)-1-(6-methoxy-4-methylpyridin-3-yl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazoleYield 47.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

To a solution of 4-{4-chloro-7-(1-ethylpropyl)-2-[(6-methoxy-4-methylpyridin-3-yl)amino]-1H-benzimidazol-1-yl}butan-1-ol (100 mg, 0.23 mmol) in pyridine (2 mL) was added methanesulfonyl chloride (0.090 mL, 1.16 mmol) dropwise at 0° C. The mixture was warmed to room temperature and stirred for 40 hr. Aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. Organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The resulting crude mesylate was dissolved in N,N-dimethylformamide (4 mL) and potassium carbonate (160 mg, 1.16 mmol) was added. The mixture was stirred at 80° C. for 3 hr. Water was added and the mixture was extracted with ethyl acetate. Organic layer was washed with water and brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 20-40% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound (45 mg, 0.109 mmol, 47%) 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 magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resulting crude mesylate was dissolved in N,N-dimethylformamide (4 mL)
  6. stirringThe mixture was stirred at 80° C. for 3 hr
  7. extractionthe mixture was extracted with ethyl acetate
  8. washOrganic layer was washed with water and brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography on silica gel eluting with a 20-40% ethyl acetate/n-hexane gradient mixture
  12. concentrationThe filtrate was concentrated in vacuo
  13. customto give the solid, which
  14. customwas recrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-4c77e0280e4d4c85a22fa7c8aba04104
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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