Potassium Carbonate → Methyl 9-chloro-1-(3,5-dichloropyridin-2-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate

HRID 1399094Notes

Reaction equation

HRID 1399094 reaction equation
CS(Cl)(=O)=O.[Cl:6][C:7]1[C:15]2[N:14]=[C:13]([NH:16][C:17]3[C:22]([Cl:23])=[CH:21][C:20]([Cl:24])=[CH:19][N:18]=3)[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.O.C(N(CC)CC)C>[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[C:22]([Cl:23])=[CH:21][C:20]([Cl:24])=[CH:19][N:18]=3)[CH2:27][CH2:26][CH2:25][N:12]21

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 68763519Methyl 4-chloro-2-[(3,5-dichloropyridin-2-yl)amino]-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate

Product 1

HCID 57786210Methyl 9-chloro-1-(3,5-dichloropyridin-2-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateYield 75%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Methanesulfonyl chloride (1.8 mL, 23.1 mmol) was added to a stirred solution of methyl 4-chloro-2-[(3,5-dichloropyridin-2-yl)amino]-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate (Reference example 123, 3.32 g, 7.73 mmol) and triethylamine (4.3 mL) in tetrahydrofuran (100 mL) at 0° C. The mixture was stirred at room temperature for 5 hr. The mixture was diluted, with aqueous sodium hydrogen carbonate, and the precipitate was collected by filtration. A mixture of the resulting mesylate and potassium carbonate (4.27 g, 30.9 mmol) in N,N-dimethylformamide (40 mL) was stirred at 80° C. for 2 hr. The mixture was diluted with water, 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 purified by flash column chromatography on silica gel eluting with a 20-50% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was washed with diisopropyl ether to give the title compound as a colorless powder (2.37 g, 5.76 mmol, 75% in 2 steps).

Workup

  1. filtrationthe precipitate was collected by filtration
  2. stirringwas stirred at 80° C. for 2 hr
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel eluting with a 20-50% ethyl acetate/n-hexane gradient mixture
  9. concentrationThe filtrate was concentrated in vacuo
  10. customto give the solid, which
  11. washwas washed with diisopropyl ether

Sources & evidence

ORD record
ord-a70cbb38595842759dfd11e26ffa810e
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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