Hydrochloric Acid → Vafidemstat

HRID 709417Notes

Reaction equation

HRID 709417 reaction equation
Cl.[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([C@@H:16]2[CH2:18][C@H:17]2[NH:19][CH2:20][C:21]2[O:25][C:24]([NH:26]C(=O)OC(C)(C)C)=[N:23][N:22]=2)=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>O1CCOCC1>[CH2:2]([O:9][C:10]1[CH:11]=[CH:12][C:13]([C@@H:16]2[CH2:18][C@H:17]2[NH:19][CH2:20][C:21]2[O:25][C:24]([NH2:26])=[N:23][N:22]=2)=[CH:14][CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86695277Tert-butyl (5-((((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-yl)carbamate

Product 1

HCID 66714983VafidemstatYield 52%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

HCl in 1, 4 dioxane (1 mL) was added to a solution of tert-butyl (5-((((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-yl)carbamate (100 mg) in 1, 4 dioxane (1 mL) at 0° C. and stirred for 18 h. After completion, the solvent was evaporated and residue was dissolved in water (10 mL), basified with Na2CO3 solution, extracted with EtOAc (3×5 mL) The combined extracts were washed with water (5 mL), brine (5 mL), dried over anhydrous Na2SO4, filtered and evaporated. The crude residue was purified by column chromatography using MeOH: CHCl3 (5:95) as eluent to afford 5-(((trans)-2-(4-(benzyloxy)phenyl)cyclopropylamino)methyl)-1,3,4-oxadiazol-2-amine (40 mg, 52%) as a white solid.

Workup

  1. customAfter completion, the solvent was evaporated
  2. dissolutionresidue was dissolved in water (10 mL)
  3. extractionextracted with EtOAc (3×5 mL) The combined extracts
  4. washwere washed with water (5 mL), brine (5 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude residue was purified by column chromatography

Sources & evidence

ORD record
ord-0f9e986d65594e9685d284f59c7860f7
Source dataset
uspto-grants-2015_11
Patent number
US09181198B2

Reaction notes

Loading…