Hydrazine → HCID 178457084, compound

HRID 240915Notes

Reaction equation

HRID 240915 reaction equation
C([O:8][C:9]1[CH:30]=[C:29]([O:31]CC2C=CC=CC=2)[C:28]([CH:39]([CH3:41])[CH3:40])=[CH:27][C:10]=1[C:11]([NH:13][C:14]1[CH:19]=CC(OC)=[C:16]([N:22]([CH3:26])[CH2:23][CH2:24][CH3:25])[CH:15]=1)=O)C1C=CC=CC=1.COC1C=CC(P2(SP(C3C=CC([O:62][CH3:63])=CC=3)(=S)S2)=S)=CC=1.[NH2:64][NH2:65].C1N=CN(C(N2C=NC=C2)=O)C=1.O1[CH2:83][CH2:82][O:81][CH2:80]C1>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[OH:62][C:63]1[N:13]([C:14]2[CH:19]=[CH:83][C:82]([O:81][CH3:80])=[C:16]([N:22]([CH3:26])[CH2:23][CH2:24][CH3:25])[CH:15]=2)[C:11]([C:10]2[CH:27]=[C:28]([CH:39]([CH3:40])[CH3:41])[C:29]([OH:31])=[CH:30][C:9]=2[OH:8])=[N:64][N:65]=1

Participants

9

Reactant 5

HCID 9321HydrazineHCID 312751,4-DioxaneHCID 682631,1'-CarbonyldiimidazoleHCID 87949Lawesson's reagentHCID 591678842,4-Bis-benzyloxy-5-isopropyl-N-[4-methoxy-3-(methylpropylamino)phenyl]benzamide

Product 1

HCID 178457084HCID 178457084, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
110 °C

Procedure

2,4-Bis-benzyloxy-5-isopropyl-N-[4-methoxy-3-(methylpropylamino)phenyl]benzamide (700 mg, 1.27 mmol) and Lawesson's reagent (0.31 g, 0.76 mmol) were dissolved in toluene (20 mL) and heated to 110° C. for 3 hrs then evaporated to dryness under reduced pressure to produce a yellow oil. This crude product was dissolved in dioxane (10 mL), anhydrous hydrazine (0.6 mL) was added and the reaction was heated to 80° C. for 30 min. After cooling, ethyl acetate (50 mL) and water (50 mL) were added. The ethyl acetate layer was washed with water (3×50 mL), dried over magnesium sulfate, filtered and evaporated to dryness to produce the crude product as a brown solid. This solid was dissolved in ethyl acetate (50 mL), CDI (0.66 g, 4.08 mmol) was added then the reaction was heated to reflux for 3 hrs. Removal of the solvent under reduced pressure followed by purification by silicagel chromatography (elution with 50% ethyl acetate/hexane) provided the desired compound as a white solid (250 mg, 33% over 3 steps).

Workup

  1. customthen evaporated to dryness under reduced pressure
  2. customto produce a yellow oil
  3. temperaturethe reaction was heated to 80° C. for 30 min
  4. temperatureAfter cooling
  5. washThe ethyl acetate layer was washed with water (3×50 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customto produce the crude product as a brown solid
  10. temperaturethe reaction was heated
  11. temperatureto reflux for 3 hrs
  12. customRemoval of the solvent under reduced pressure
  13. customfollowed by purification by silicagel chromatography (elution with 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-58b45a1ac4584135892b4e14788d99c4
Source dataset
uspto-grants-2014_02
Patent number
US08648104B2

Reaction notes

Loading…