Hydrochloric Acid → 2,2,2-Trifluoro-1-[9-methoxy-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]ethanol

HRID 1399374Notes

Reaction equation

HRID 1399374 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH3:19][O:20][C:21]1[CH:22]=[CH:23][C:24]([CH:44]=[O:45])=[C:25]2[C:29]=1[N:28]=[C:27]1[N:30]([C:34]3[C:35]([CH3:43])=[N:36][C:37]([O:41][CH3:42])=[N:38][C:39]=3[CH3:40])[CH2:31][CH2:32][CH2:33][N:26]21.C[Si](C)(C)[C:48]([F:51])([F:50])[F:49].Cl.C(=O)([O-])O.[Na+]>O1CCCC1>[F:49][C:48]([F:51])([F:50])[CH:44]([C:24]1[C:25]2[N:26]3[CH2:33][CH2:32][CH2:31][N:30]([C:34]4[C:35]([CH3:43])=[N:36][C:37]([O:41][CH3:42])=[N:38][C:39]=4[CH3:40])[C:27]3=[N:28][C:29]=2[C:21]([O:20][CH3:19])=[CH:22][CH:23]=1)[OH:45]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 577857769-Methoxy-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbaldehyde

Product 1

HCID 441565002,2,2-Trifluoro-1-[9-methoxy-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]ethanolYield 40.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Tetrabutylammonium fluoride (1.0 M solution in tetrahydrofuran, 0.13 mL, 0.13 mmol) was added to a stirred solution of the 9-methoxy-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbaldehyde (467 mg) and trimethyl(trifluoromethyl)silane (361 mg, 2.54 mmol) in tetrahydrofuran (5.0 mL) at 0° C., and the mixture was stirred at 0° C. for 30 min, at room temperature for 70 min. 1N Hydrochloric acid (5.0 mL) was added to the mixture at room temperature, and the mixture was stirred for 15 min. The mixture was neutralized with saturated 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 purified by flash column chromatography on silica gel eluting with a 0-7% methanol/ethyl acetate gradient mixture. The eluate was concentrated in vacuo to give the title compound as a colorless solid (224 mg, 0.512 mmol).

Workup

  1. stirringthe mixture was stirred for 15 min
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel eluting with a 0-7% methanol/ethyl acetate gradient mixture
  8. concentrationThe eluate was concentrated in vacuo

Sources & evidence

ORD record
ord-2b41761bd2e64fb1a6e65dc89bf758f5
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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