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

HRID 1399108Notes

Reaction equation

HRID 1399108 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([CH:43]=[O:44])=[C:24]2[C:28]=1[N:27]=[C:26]1[N:29]([C:33]3[C:34]([CH3:42])=[N:35][C:36]([O:40][CH3:41])=[N:37][C:38]=3[CH3:39])[CH2:30][CH2:31][CH2:32][N:25]21.C[Si](C)(C)[C:47]([F:50])([F:49])[F:48].Cl.C(=O)([O-])O.[Na+]>O1CCCC1>[Cl:19][C:20]1[C:28]2[N:27]=[C:26]3[N:29]([C:33]4[C:34]([CH3:42])=[N:35][C:36]([O:40][CH3:41])=[N:37][C:38]=4[CH3:39])[CH2:30][CH2:31][CH2:32][N:25]3[C:24]=2[C:23]([CH:43]([OH:44])[C:47]([F:50])([F:49])[F:48])=[CH:22][CH:21]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 577859669-Chloro-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbaldehyde

Product 1

HCID 577860611-[9-Chloro-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2,2,2-trifluoroethanolYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Tetrabutylammonium fluoride (1.0 M solution in tetrahydrofuran, 1.1 mL, 1.1 mmol) was added dropwise to a stirred solution of 9-chloro-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbaldehyde (4.12 g, 11.1 mmol) and trimethyl(trifluoromethyl)silane (3.16 g, 22.2 mmol) in tetrahydrofuran (45 mL) at 0° C., and the mixture was stirred at 0° C. for 20 min. 1N hydrochloric acid (35 mL) was added to the mixture at 0° C., and the mixture was stirred at 0° C. for 30 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 75-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was washed with ethyl acetate/diisopropyl ether to give the title compound as a colorless powder (3.96, 8.96 mmol, 81%).

Workup

  1. stirringthe mixture was stirred at 0° C. for 30 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 75-100% ethyl acetate/n-hexane gradient mixture
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto give the solid, which
  10. washwas washed with ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-2384eddce34a4fc4aa0fb7528a94838f
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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