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

HRID 1399081Notes

Reaction equation

HRID 1399081 reaction equation
CS(Cl)(=O)=O.[Cl:6][C:7]1[C:15]2[N:14]=[C:13]([NH:16][C:17]3[CH:18]=[N:19][C:20]([N:24]([CH3:26])[CH3:25])=[CH:21][C:22]=3[CH3:23])[N:12]([CH2:27][CH2:28][CH2:29]O)[C:11]=2[C:10]([C:31]([O:33][CH3:34])=[O:32])=[CH:9][CH:8]=1.S([O-])(=O)(=O)C.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.CN(C)C=O.C(=O)([O-])O.[Na+].C(N(CC)CC)C>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([C:31]([O:33][CH3:34])=[O:32])=[C:11]2[C:15]=1[N:14]=[C:13]1[N:16]([C:17]3[CH:18]=[N:19][C:20]([N:24]([CH3:26])[CH3:25])=[CH:21][C:22]=3[CH3:23])[CH2:29][CH2:28][CH2:27][N:12]21

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 68765749methyl 4-chloro-2-{[6-(dimethylamino)-4-methylpyridin-3-yl]amino}-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate

Product 1

HCID 57786377Methyl 9-chloro-1-[6-(dimethylamino)-4-methylpyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateYield 58%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Methanesulfonyl chloride (1.7 mL, 21.0 mmol) was added to a stirred solution of methyl 4-chloro-2-{[6-(dimethylamino)-4-methylpyridin-3-yl]amino}-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate (Reference example 119, 2.20 g, 5.26 mmol) and triethylamine (3.7 mL) in tetrahydrofuran (26 mL) at 0° C. The mixture was stirred at room temperature for 13 hr, and concentrated in vacuo. A mixture of the resulting mesylate, potassium carbonate (2.18 g, 15.8 mmol) in N,N-dimethylformamide (30 mL) was stirred at 80° 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 (1.22 g, 3.05 mmol, 58% in 2 steps).

Workup

  1. concentrationconcentrated in vacuo
  2. stirringwas stirred at 80° C. for 4 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. washThe residue was washed with diisopropyl ether

Sources & evidence

ORD record
ord-da830f660f1d4cd2826f81e7a7fa05bf
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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