Imidazole → HCID 59331671, compound

HRID 1255847Notes

Reaction equation

HRID 1255847 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:26])[C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([CH3:25])[CH:20]=3)[CH:14]=[CH:15][CH:16]=2)[CH3:10])[CH:5]=[N:4][CH:3]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[NH:73]1[CH:77]=[CH:76][N:75]=[CH:74]1.CC(C)([O-])C.[Na+]>CN(C)C=O.C(=O)([O-])O.[Na+].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:73]1([C:2]2[N:7]=[C:6]([NH:8][C@H:9]([C:11]3[CH:12]=[C:13]([NH:17][C:18](=[O:26])[C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([CH3:25])[CH:20]=4)[CH:14]=[CH:15][CH:16]=3)[CH3:10])[CH:5]=[N:4][CH:3]=2)[CH:77]=[CH:76][N:75]=[CH:74]1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 25218459HCID 25218459, compound

Product 1

HCID 59331671HCID 59331671, compoundYield 40.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of (S)—N-(3-(1-(6-chloropyrazin-2-ylamino)ethyl)phenyl)-3-methylbenzamide (92 mg, 0.25 mmol), palladium acetate (3 mg, 0.0125 mmol), (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (8 mg, 0.0125 mmol), imidazole (17 mg, 0.25 mmol) and sodium tert-butoxide (36 mg, 0.375 mmol) in N,N-dimethyl formamide (0.5 mL) was heated in a microwave reactor at 180° C. for 20 minutes. After this time the mixture was allowed to cool to room temperature and was diluted with saturated aqueous sodium hydrogen carbonate (10 mL), extracted with ethyl acetate (3×15 mL), washed with brine (15 mL), dried (Na2SO4) and concentrated under reduced pressure to give a yellow oil which was purified by flash chromatography (silica, ethyl acetate/methanol) to give (S)—N-(3-(1-(6-(1H-imidazol-1-yl)pyrazin-2-ylamino)ethyl)phenyl)-3-methylbenzamide (40 mg, 40%) as a brown solid.

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with ethyl acetate (3×15 mL)
  3. washwashed with brine (15 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customto give a yellow oil which
  7. customwas purified by flash chromatography (silica, ethyl acetate/methanol)

Sources & evidence

ORD record
ord-844f52a03c334a6bacb63efc1496d4d9
Source dataset
uspto-grants-2013_06
Patent number
US08461161B2

Reaction notes

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