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

HRID 1629010Notes

Reaction equation

HRID 1629010 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][C:12]3[C:13]([C:20]([F:23])([F:22])[F:21])=[N:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=3)[N:7]([CH2:24][CH2:25][CH2:26]O)[C:6]=2[C:5]([C:28]([O:30][CH3:31])=[O:29])=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.C(=O)([O-])O.[Na+].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.CN(C)C=O.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:28]([O:30][CH3:31])=[O:29])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:12]3[C:13]([C:20]([F:22])([F:21])[F:23])=[N:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=3)[CH2:26][CH2:25][CH2:24][N:7]21

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 68760595Methyl 4-chloro-1-(3-hydroxypropyl)-2-{[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]amino}-1H-benzimidazole-7-carboxylate

Product 1

HCID 57786121Methyl 9-chloro-1-[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateYield 90.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of methyl 4-chloro-1-(3-hydroxypropyl)-2-{[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]amino}-1H-benzimidazole-7-carboxylate (1.50 g, 3.27 mmol) and triethylamine (0.91 mL, 6.53 mmol) in tetrahydrofuran (30 mL) was added methanesulfonyl chloride (0.38 mL, 4.90 mmol) at 0° C. The mixture was stirred at 0° C. for 0.5 hr. Aqueous sodium hydrogen carbonate was added to the reaction mixture at 0° C., and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. A mixture of the residue and potassium carbonate (1.81 g, 13.1 mmol) in N,N-dimethylformamide (30 mL) was stirred at 80° C. for 13 hr. Water was added to the reaction mixture at room temperature and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium 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 to give the title compound (1.33 g, 2.95 mmol, 90%) as a white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. stirringwas stirred at 80° C. for 13 hr
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with water and brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography on silica gel eluting with a 30-100% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-96379e4577384391ad37e4d268e85978
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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