Trifluoroacetic acid → HCID 57786108, compound

HRID 1399133Notes

Reaction equation

HRID 1399133 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([CH3:25])=[N:17][C:18]([CH:22]5[CH2:24][CH2:23]5)=[N:19][C:20]=4[CH3:21])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:26]([OH:31])[C:27]([F:30])([F:29])[F:28])=[CH:4][CH:3]=1.[OH-].[Na+].[F:34][C:35](F)([F:39])C(O)=O>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.O1CCCC1.[Cl-].[NH4+]>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:20]([CH3:21])=[N:19][C:18]([CH:22]5[CH2:23][CH2:24]5)=[N:17][C:16]=4[CH3:25])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:26]([O:31][CH:35]([F:39])[F:34])[C:27]([F:29])([F:28])[F:30])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 57786045HCID 57786045, compound

Product 1

HCID 57786108HCID 57786108, compound

Reagents, catalysts & solvents 3

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A mixture of 1-[9-chloro-1-(2-cyclopropyl-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2,2,2-trifluoroethanol (305 mg, 0.675 mmol), benzyltriethylammonium chloride (7.7 mg, 0.0338 mmol), and 8N sodium hydroxide (2.7 mL) in tetrahydrofuran (2.7 mL) was stirred at room temperature under chloro(difluoro)methane atmosphere for 60 min. The mixture was diluted with aqueous saturated ammonium chloride, 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 60-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was purified by preparative HPLC to give a mixture containing an intermediate of the title compound as the trifluoroacetic acid salt. The mixture was washed with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound as a colorless crystal (98.2 mg, 0.196 mmol, 29%).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel eluting with a 60-100% ethyl acetate/n-hexane gradient mixture
  7. concentrationThe filtrate was concentrated in vacuo
  8. customto give the solid, which
  9. customwas purified by preparative HPLC
  10. customto give a mixture

Sources & evidence

ORD record
ord-cfda4a1170fe4872a9f7b9147e85ebf2
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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