Cesium carbonate → HCID 11531718, compound

HRID 1867276Notes

Reaction equation

HRID 1867276 reaction equation
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.Br[C:48]1[CH:67]=[CH:66][C:51]2[C:52]([C:55]([N:57]3[CH:63]4[CH2:64][CH2:65][N:60]([CH2:61][CH2:62]4)[CH2:59][CH2:58]3)=[O:56])=[N:53][S:54][C:50]=2[CH:49]=1.[CH:68]([N:71]1[CH2:75][CH2:74][NH:73][C:72]1=[O:76])([CH3:70])[CH3:69].C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[N:60]12[CH2:65][CH2:64][CH:63]([CH2:62][CH2:61]1)[N:57]([C:55]([C:52]1[C:51]3[CH:66]=[CH:67][C:48]([N:73]4[CH2:74][CH2:75][N:71]([CH:68]([CH3:70])[CH3:69])[C:72]4=[O:76])=[CH:49][C:50]=3[S:54][N:53]=1)=[O:56])[CH2:58][CH2:59]2

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 115751596-Bromo-3-(1,4-diazabicyclo[3.2.2]non-4-ylcarbonyl)-1,2-benzisothiazoleHCID 217190151-(Propan-2-yl)imidazolidin-2-one

Product 1

HCID 11531718HCID 11531718, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of toluene (8 mL) and (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.2 mmol) was degassed with nitrogen for 4 minutes, then heated at 80° C. until the (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl dissolved completely. The solution was allowed to cool to rt and palladium acetate (0.09 mmol) was added. The mixture was stirred until the palladium acetate completely dissolved. The resultant yellow solution was added to a mixture of 6-bromo-3-(1,4-diazabicyclo[3.2.2]non-4-ylcarbonyl)-1,2-benzisothiazole (0.33 mmol), 1-isopropylimidazolidin-2-one (0.5 mmol) and cesium carbonate (0.39 mmol) under a nitrogen atmosphere. The reaction mixture was subjected to microwave radiation at 150° C. for 360 s. The inorganic precipitates were removed by filtration, and the filtrate was concentrated. The residue was purified by preparative HPLC to provide the product in 75% yield. 1H NMR (CD3OD) δ 8.17 (s, 1H), 8.03-7.93 (m, 2H), 4.30-4.05 (m, 2H), 3.92 (t, J=7.14, 2H), 3.70 (t, J=5.7, 2H), 3.54 (t, J=7.1, 2H), 3.20-3.00 (m, 6H), 1.22 (d, J=6.78, 3 6H); LC/MS (EI) tR3.10 min, m/z 415 (M++1).

Workup

  1. customwas degassed with nitrogen for 4 minutes
  2. dissolutiondissolved completely
  3. temperatureto cool to rt
  4. dissolutioncompletely dissolved
  5. customat 150° C.
  6. customfor 360 s
  7. customThe inorganic precipitates
  8. customwere removed by filtration
  9. concentrationthe filtrate was concentrated
  10. customThe residue was purified by preparative HPLC
  11. customto provide the product in 75% yield

Sources & evidence

ORD record
ord-b76cc778766341ccba7f0342866f184f
Source dataset
uspto-grants-2009_12
Patent number
US07632831B2

Reaction notes

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