Cesium carbonate → 2-[(Phenylmethyl)oxy]-N-3-pyridinyl-5-[(3R,5S)-3,4,5-trimethyl-1-piperazinyl]benzamide

HRID 1623841Notes

Reaction equation

HRID 1623841 reaction equation
[CH3:1][N:2]1[C@@H:7]([CH3:8])[CH2:6][NH:5][CH2:4][C@H:3]1[CH3:9].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Br[C:63]1[CH:64]=[CH:65][C:66]([O:78][CH2:79][C:80]2[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=2)=[C:67]([CH:77]=1)[C:68]([NH:70][C:71]1[CH:72]=[N:73][CH:74]=[CH:75][CH:76]=1)=[O:69]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:80]1([CH2:79][O:78][C:66]2[CH:65]=[CH:64][C:63]([N:5]3[CH2:6][C@H:7]([CH3:8])[N:2]([CH3:1])[C@H:3]([CH3:9])[CH2:4]3)=[CH:77][C:67]=2[C:68]([NH:70][C:71]2[CH:72]=[N:73][CH:74]=[CH:75][CH:76]=2)=[O:69])[CH:81]=[CH:82][CH:83]=[CH:84][CH:85]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 30720221(2R,6S)-1,2,6-TrimethylpiperazineHCID 369825032-(benzyloxy)-5-bromo-N-(pyridin-3-yl)benzamide

Product 1

HCID 699370442-[(Phenylmethyl)oxy]-N-3-pyridinyl-5-[(3R,5S)-3,4,5-trimethyl-1-piperazinyl]benzamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

(2R,6S)-1,2,6-Trimethylpiperazine (105 mg, 0.52 mmol), cesium carbonate (680 mg, 2.09 mmol), BINAP (2.44 mg, 3.91 μmol) and Pd2(dba)3 (1.20 mg, 1.30 μmol) were added to 5-bromo-2-[(phenylmethyl)oxy]-N-3-pyridinylbenzamide (may be prepared as described in example 2; 200 mg, 0.52 mmol) in anhydrous toluene (5 ml), and the mixture was heated to reflux overnight. The reaction mixture was evaporated under reduced pressure. Water (50 ml) was added to the residue and the mixture was extracted with ethyl acetate (3×50 ml). The organics were combined and evaporated, and the residue purified by MDAP twice to yield the title compound. 180 mg.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux overnight
  3. customThe reaction mixture was evaporated under reduced pressure
  4. additionWater (50 ml) was added to the residue
  5. extractionthe mixture was extracted with ethyl acetate (3×50 ml)
  6. customevaporated
  7. customthe residue purified by MDAP twice

Sources & evidence

ORD record
ord-a472b823caff4ec7983ea2a51e9c080b
Source dataset
uspto-grants-2014_07
Patent number
US08778939B2

Reaction notes

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