Isopropyl iodide → HCID 57786095, compound

HRID 1399239Notes

Reaction equation

HRID 1399239 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13]3=[N:14][C:15]4[C:20]([Cl:21])=[CH:19][CH:18]=[C:17]([CH:22]([O:27][CH:28]([F:30])[F:29])[C:23]([F:26])([F:25])[F:24])[C:16]=4[N:12]3[CH2:11][CH2:10][CH2:9]2)=[C:4]([CH3:31])[CH:3]=1.[OH-].[K+].[C:34](P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)([CH3:37])(C)[CH3:35].C(=O)([O-])[O-:69].[K+].[K+].IC(C)C>COCCOC.[Cl-].[Na+].O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Cl:21][C:20]1[C:15]2[N:14]=[C:13]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([O:69][CH:34]([CH3:37])[CH3:35])=[CH:3][C:4]=4[CH3:31])[CH2:9][CH2:10][CH2:11][N:12]3[C:16]=2[C:17]([CH:22]([O:27][CH:28]([F:30])[F:29])[C:23]([F:26])([F:25])[F:24])=[CH:18][CH:19]=1

Participants

10

Reactant 5

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 57785911HCID 57785911, compound

Product 1

HCID 57786095HCID 57786095, compoundYield 60%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 57417360Sodium chloride; waterSolvent2×

Conditions

Temperature
100 °C

Procedure

Under nitrogen atmosphere, to a suspension of 1-(4-bromo-2-methylphenyl)-9-chloro-6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole (0.20 g, 0.38 mmol), potassium hydroxide (64.2 mg, 1.14 mmol), water (2 mL) and di-tert-butyl[3,4,5,6-tetramethyl-2′,4′,6′-tri(propan-2-yl)biphenyl-2-yl]phosphane (73.3 mg, 0.15 mmol) in 1,2-dimethoxyethane (2 mL) was added tris(dibenzylideneacetone)dipalladium(0) (34.9 mg, 0.04 mmol), and the mixture was stirred at 100° C. for 1 h. The reaction mixture was diluted with brine at room temperature, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with brine, and concentrated in vacuo. To a suspension of the residue in N,N-dimethylformamide (4 mL) was added potassium carbonate (35.5 mg, 0.26 mmol), and the mixture was stirred at 0° C. for 15 min. To the reaction mixture was added 2-iodopropane (0.04 mL, 0.42 mmol) at 0° C., and the mixture was stirred at room temperature for 17 h. The reaction mixture was warmed up at 60° C. and stirred at 60° C. for 25 h. The reaction mixture was diluted with brine, and the mixture was 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 10-20% ethyl acetate/n-hexane gradient mixture. The desired fractions were concentrated in vacuo. The residual solid was recrystallized from ethyl acetate/n-hexane to give the title compound as a colorless crystal (43.8 mg, 0.09 mmol, 14%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. concentrationconcentrated in vacuo
  4. additionTo a suspension of the residue in N,N-dimethylformamide (4 mL)
  5. stirringthe mixture was stirred at 0° C. for 15 min
  6. stirringthe mixture was stirred at room temperature for 17 h
  7. temperatureThe reaction mixture was warmed up at 60° C.
  8. stirringstirred at 60° C. for 25 h
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe combined organic layer was washed with brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash column chromatography on silica gel eluting with a 10-20% ethyl acetate/n-hexane gradient mixture
  15. concentrationThe desired fractions were concentrated in vacuo
  16. customThe residual solid was recrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-eeb23277a03a4f82b319d55fadb05464
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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