Benzophenone imine → HCID 87170790, compound

HRID 1912458Notes

Reaction equation

HRID 1912458 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2([CH3:18])[N:13]=[C:12]([NH2:14])[CH2:11][N:10]3[N:15]=[CH:16][CH:17]=[C:9]23)[CH:5]=[CH:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].[C:71](=[NH:84])([C:78]1[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=1)[C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=1>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].C1(C)C=CC=CC=1>[C:71](=[N:84][C:2]1[CH:3]=[C:4]([C:8]2([CH3:18])[N:13]=[C:12]([NH2:14])[CH2:11][N:10]3[N:15]=[CH:16][CH:17]=[C:9]23)[CH:5]=[CH:6][CH:7]=1)([C:78]1[CH:79]=[CH:80][CH:81]=[CH:82][CH:83]=1)[C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=1

Participants

8

Reactant 4

HCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 66825611HCID 66825611, compound

Product 1

HCID 87170790HCID 87170790, compoundYield 71.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Toluene (10 mL) was added to a mixture of rac-4-(3-bromo-phenyl)-4-methyl-4,7-dihydro-pyrazolo[1,5-a]pyrazin-6-ylamine (0.39 g, 1.28 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.12 g, 0.13 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.24 g, 0.38 mmol) and sodium tert-butoxide (0.22 g, 2.3 mmol) in a sealed tube and under nitrogen at room temperature. The mixture was flushed with nitrogen for a few minutes and then benzophenone imine (0.43 mL, 2.56 mmol) was added and the mixture was stirred at 100° C. for 2 hours. After cooling the mixture was diluted with water and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in methanol in DCM 0/100 to 3/97). The desired fractions were collected and concentrated in vacuo to yield rac-4-[3-(benzhydrylidene-amino)-phenyl]-4-methyl-4,7-dihydro-pyrazolo[1,5-a]pyrazin-6-ylamine (0.37 g, 70% yield) as a yellow foam.

Workup

  1. customThe mixture was flushed with nitrogen for a few minutes
  2. temperatureAfter cooling the mixture
  3. extractionextracted with DCM
  4. customThe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvents evaporated in vacuo
  8. customThe crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in methanol in DCM 0/100 to 3/97)
  9. customThe desired fractions were collected
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0187970dea9142e4893afe80afb5dd4c
Source dataset
uspto-grants-2013_12
Patent number
US08609660B2

Reaction notes

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