Potassium Carbonate → Methyl 9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate

HRID 1399041Notes

Reaction equation

HRID 1399041 reaction equation
CS(Cl)(=O)=O.[Cl:6][C:7]1[C:15]2[N:14]=[C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=3[Cl:24])[N:12]([CH2:25][CH2:26][CH2:27]O)[C:11]=2[C:10]([C:29]([O:31][CH3:32])=[O:30])=[CH:9][CH:8]=1.S([O-])(=O)(=O)C.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.C(=O)([O-])O.[Na+].CN(C)C=O.C(N(CC)CC)C.N1C=CC=CC=1>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([C:29]([O:31][CH3:32])=[O:30])=[C:11]2[C:15]=1[N:14]=[C:13]1[N:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=3[Cl:24])[CH2:27][CH2:26][CH2:25][N:12]21

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 68762786Methyl 4-chloro-2-[(2,4-dichlorophenyl)amino]-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate

Product 1

HCID 57785909Methyl 9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateYield 87.4%

Reagents, catalysts & solvents 5

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 516892Sodium BicarbonateSolvent2×

Conditions

Temperature
0 °C

Procedure

Methanesulfonyl chloride (11.3 mL, 143 mmol) was added to a stirred solution of methyl 4-chloro-2-[(2,4-dichlorophenyl)amino]-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate (Reference example 117, 15.3 g, 35.7 mmol), pyridine (50 mL) and triethylamine (25 mL) in tetrahydrofuran (100 mL) at 0° C. The mixture was stirred at 0° C. for 13 hr, and diluted with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. A mixture of the resulting mesylate and potassium carbonate (14.7 g, 106 mmol) in N,N-dimethylformamide (60 mL) was stirred at 70° C. for 4 hr. The mixture was diluted with aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was washed with diisopropyl ether to give the title compound as a colorless powder (12.8 g, 31.2 mmol, 87% in 2 steps).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. stirringwas stirred at 70° C. for 4 hr
  7. extractionextracted with ethyl acetate
  8. washThe combined organic layer was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. washThe residue was washed with diisopropyl ether

Sources & evidence

ORD record
ord-b5517586e9c64fe795c809532eb48dbd
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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