Triethylamine → Methyl 9-chloro-1-(6-methoxy-2-methylpyridin-3-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate

HRID 1399167Notes

Reaction equation

HRID 1399167 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][C:12]3[C:13]([CH3:20])=[N:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=3)[N:7]([CH2:21][CH2:22][CH2:23]O)[C:6]=2[C:5]([C:25]([O:27][CH3:28])=[O:26])=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:25]([O:27][CH3:28])=[O:26])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:12]3[C:13]([CH3:20])=[N:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=3)[CH2:23][CH2:22][CH2:21][N:7]21

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 68760757HCID 68760757, compound

Product 1

HCID 57786032Methyl 9-chloro-1-(6-methoxy-2-methylpyridin-3-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-chloro-1-(3-hydroxypropyl)-2-[(6-methoxy-2-methylpyridin-3-yl)amino]-1H-benzimidazole-7-carboxylate (Reference example 156, 6.40 g, 15.81 mmol) in tetrahydrofuran (42.0 mL) were added triethylamine (4.42 mL, 31.62 mmol) and methanesulfonyl chloride (1.84 mL, 23.71 mmol) at 0° C. The reaction mixture was stirred at room temperature for 1.5 hrs. The mixture was quenched with aqueous sodium hydrogen carbonate and extracted with ethyl acetate (×3). The combined organic layer was washed with brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The resulting mesylate was dissolved into N,N-dimethylformamide (67.0 mL) and to the solution was added potassium carbonate (4.27 g, 31.62 mmol). The mixture was stirred at 70° C. for 4 hrs. After cooling, the mixture was diluted with water. The generated precipitate was collected by filtration and washed with diisopropyl ether to give the title compound as a colorless solid (5.50 g, 14.22 mmol, 90%).

Workup

  1. customThe mixture was quenched with aqueous sodium hydrogen carbonate
  2. extractionextracted with ethyl acetate (×3)
  3. washThe combined organic layer was washed with brine (×1)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting mesylate was dissolved into N,N-dimethylformamide (67.0 mL) and to the solution
  8. stirringThe mixture was stirred at 70° C. for 4 hrs
  9. temperatureAfter cooling
  10. filtrationThe generated precipitate was collected by filtration
  11. washwashed with diisopropyl ether

Sources & evidence

ORD record
ord-b4675c700af94c9fb0fb3febecf76f6d
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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