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

HRID 1399098Notes

Reaction equation

HRID 1399098 reaction equation
CS(Cl)(=O)=O.[Cl:6][C:7]1[C:15]2[N:14]=[C:13]([NH:16][C:17]3[C:18]([O:26][CH3:27])=[N:19][C:20]([CH3:25])=[N:21][C:22]=3[O:23][CH3:24])[N:12]([CH2:28][CH2:29][CH2:30]O)[C:11]=2[C:10]([C:32]([O:34][CH3:35])=[O:33])=[CH:9][CH:8]=1.S([O-])(=O)(=O)C.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.CN(C)C=O.O.C(N(CC)CC)C>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([C:32]([O:34][CH3:35])=[O:33])=[C:11]2[C:15]=1[N:14]=[C:13]1[N:16]([C:17]3[C:22]([O:23][CH3:24])=[N:21][C:20]([CH3:25])=[N:19][C:18]=3[O:26][CH3:27])[CH2:30][CH2:29][CH2:28][N:12]21

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 68762737methyl 4-chloro-2-[(4,6-dimethoxy-2-methylpyrimidin-5-yl)amino]-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate

Product 1

HCID 57785929Methyl 9-chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateYield 80.3%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

Methanesulfonyl chloride (0.11 mL, 1.43 mmol) was added to a stirred solution of methyl 4-chloro-2-[(4,6-dimethoxy-2-methylpyrimidin-5-yl)amino]-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate (Reference example 124, 208 mg, 0.477 mmol) and triethylamine (0.27 mL) in tetrahydrofuran (4.0 mL) at 0° C. The mixture was stirred at 0° C. for 2 hr, and concentrated in vacuo. A mixture of the resulting mesylate and potassium carbonate (264 mg, 1.91 mmol) in N,N-dimethylformamide (5.0 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 washed with diisopropyl ether to give the title compound as a colorless powder (160 mg, 0.383 mmol, 80% in 2 steps).

Workup

  1. concentrationconcentrated in vacuo
  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. washThe residue was washed with diisopropyl ether

Sources & evidence

ORD record
ord-2dcba130da034cd3aaa96c177cde2895
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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