Acetic Acid → HCID 131732506, compound

HRID 1854735Notes

Reaction equation

HRID 1854735 reaction equation
[CH3:1][C:2]([CH3:14])([S:4]([NH:6][C:7]([CH3:13])([CH3:12])/[C:8](=[N:10]/[OH:11])/[NH2:9])=[O:5])[CH3:3].[CH3:15]C(O)=O>>[CH3:3][C:2]([S:4]([NH:6][C:7]([CH:8]1[N:9]=[CH:15][O:11][NH:10]1)([CH3:13])[CH3:12])=[O:5])([CH3:14])[CH3:1]

Participants

3

Reactant 2

HCID 176Acetic AcidHCID 140653217HCID 140653217, compound

Product 1

HCID 131732506HCID 131732506, compoundYield 18%

Procedure

(Z)-2-(1,1-dimethylethylsulfinamido)-N′-hydroxy-2-methylpropanimidamide (140 mg, 0.633 mmol) in AcOH (4 ml) was treated with [diethoxy(2H)methoxy]ethane (0.106 ml, 0.633 mmol) at rt. The reaction was allowed to stir at rt for 16 h. LCMS showed a major peak with the expected M+H. The reaction was concentrated to dryness azeotroping with toluene 3×. The resulting oil was purified on silica gel (Biotage, EtOAc/hexanes gradient (Rf ˜0.2 in 70% EtOAc/Hex, visualized with permanganate stain), to give the expected product (27 mg, 0.12 mmol, 18% yield) consistent by LCMS. LC-MS retention time: 1.47 min; m/z (MH+): 233. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u C18 2.0×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% MeOH/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% MeOH/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. Step 2: Preparation of the titled compound: 2-[(2H)-1,2,4-oxadiazol-3-yl]propan-2-amine hydrochloride HCl (1.0 mL, 1.9 mmol) (2 M in Et2O) was added to a stirring solution of 2-methyl-N-{2-[(2H)-1,2,4-oxadiazol-3-yl]propan-2-yl}propane-2-sulfinamide (27 mg, 0.12 mmol) in MeOH (1 mL) at rt. The reaction was allowed to stir for 2 h and then concentrated azeotroping with toluene to give the expected product (15 mg, 0.091 mmol, 78% yield) consistent by NMR. 1H NMR (400 MHz, METHANOL-d4) δ 1.77 (s, 6H).

Workup

  1. concentrationThe reaction was concentrated to dryness
  2. customazeotroping with toluene 3×
  3. customThe resulting oil was purified on silica gel (Biotage, EtOAc/hexanes gradient (Rf ˜0.2 in 70% EtOAc/Hex, visualized with permanganate stain)

Sources & evidence

ORD record
ord-5aaa4756ad9d480390d6eb6fcd715583
Source dataset
uspto-grants-2015_02
Patent number
US08962651B2

Reaction notes

Loading…