Dimethylformamide → HCID 68663362, compound

HRID 733338Notes

Reaction equation

HRID 733338 reaction equation
[O:1]=[C:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.[CH:8]1C=N[C:11]2N(O)N=N[C:10]=2[CH:9]=1.CN(C(ON1N=NC2C=[CH:30][CH:31]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N([CH:48]([CH3:50])C)CC)(C)C.[CH2:51]([O:58][C:59](=[O:84])[N:60]([CH2:70][CH:71]([OH:83])[CH:72]([NH2:82])[CH2:73][C:74]1[CH:79]=[C:78]([F:80])[CH:77]=[C:76]([F:81])[CH:75]=1)[CH2:61][C:62]1[CH:67]=[CH:66][C:65](CC)=[CH:64][CH:63]=1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1.CN(C=[O:89])C>C(Cl)Cl.CO.CCCCCCC>[CH2:51]([O:58][C:59](=[O:84])[N:60]([CH2:70][CH:71]([OH:83])[CH:72]([NH:82][C:30](=[O:89])[CH2:31][N:6]1[CH2:5][CH2:4][N:3]([CH2:11][CH2:10][CH2:9][CH3:8])[C:2](=[O:1])[CH2:7]1)[CH2:73][C:74]1[CH:75]=[C:76]([F:81])[CH:77]=[C:78]([F:80])[CH:79]=1)[CH2:61][C:62]1[CH:63]=[CH:64][CH:65]=[C:66]([CH2:48][CH3:50])[CH:67]=1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1

Participants

9

Reactant 6

HCID 6228Dimethylformamide2×HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 231360Piperazin-2-oneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68662832HCID 68662832, compound

Product 1

HCID 68663362HCID 68663362, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 8900HeptaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

Oxopiperazine vii (0.16 g, 0.75 mmol) is combined with HOAt (0.11 g, 0.81 mmol) and HATU (0.31 g, 0.82 mmol) in 5 mL of dry DMF at 0° C. under N2. After 0.5 h a solution of diisopropylethylamine (0.39 mL, 2.2 mmol) and [3-amino-4-(3,5-difluoro-phenyl)-2-hydroxy-butyl]-(4-ethyl-benzyl)-carbamic acid benzyl ester (0.38 g, 0.81 mmol) in 5 mL anhydrous DMF is added. The solution is allowed to stir for 16 h at ambient temperature. The reaction is quenched by the addition of 1M HCl and diluted with ethyl acetate. The phases are separated and the aqueous layer is extracted with ethyl acetate. The combined organics are washed with 1M HCl, saturated aqueous NaHCO3 and dried over Na2SO4. The mixture is filtered and concentrated to give an oil which is purified by flash chromatography on a BIOTAGE 40S column eluting with 400 mL of heptane, followed by 1 L of 2/1: heptane/EtOAC and 97/3: CH2Cl2/MeOH to give H as a yellow oil (0.2 g, 0.3 mmol, 40%). (MS:M+H:665.3)

Workup

  1. customThe reaction is quenched by the addition of 1M HCl
  2. additiondiluted with ethyl acetate
  3. customThe phases are separated
  4. extractionthe aqueous layer is extracted with ethyl acetate
  5. washThe combined organics are washed with 1M HCl, saturated aqueous NaHCO3
  6. dry with materialdried over Na2SO4
  7. filtrationThe mixture is filtered
  8. concentrationconcentrated
  9. customto give an oil which
  10. customis purified by flash chromatography on a BIOTAGE 40S column
  11. washeluting with 400 mL of heptane

Sources & evidence

ORD record
ord-240a4bc427444dd7bb9e70961e8ff252
Source dataset
uspto-grants-2009_09
Patent number
US07589094B2

Reaction notes

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