Dimethylformamide dimethyl acetal → N-(1-(1,2,4-oxadiazol-3-yl)cyclobutyl)-2-methylpropane-2-sulfinamide

HRID 1854744Notes

Reaction equation

HRID 1854744 reaction equation
[CH3:1][C:2]([CH3:15])([S:4]([NH:6][C:7]1(/[C:11](=[N:13]/[OH:14])/[NH2:12])[CH2:10][CH2:9][CH2:8]1)=[O:5])[CH3:3].[CH3:16]OC(OC)N(C)C>O1CCOCC1>[O:14]1[CH:16]=[N:12][C:11]([C:7]2([NH:6][S:4]([C:2]([CH3:15])([CH3:1])[CH3:3])=[O:5])[CH2:10][CH2:9][CH2:8]2)=[N:13]1

Participants

4

Reactant 2

HCID 78373Dimethylformamide dimethyl acetalHCID 904023191-(tert-butylsulfinylamino)-N'-hydroxycyclobutane-1-carboximidamide

Product 1

HCID 90402384N-(1-(1,2,4-oxadiazol-3-yl)cyclobutyl)-2-methylpropane-2-sulfinamideYield 14.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

(Z)-1-(1,1-dimethylethylsulfinamido)-N′-hydroxycyclobutanecarboximidamide (300 mg, 1.29 mmol) was taken up in dioxane (6 ml) and treated with N,N-Dimethylformamide dimethyl acetal (2.6 ml, 19 mmol) at rt. The reaction was then heated to 70° C. for 4 h. LCMS showed that starting material had been consumed. The expected M+H of 244 was observed in one of the minor peaks. The reaction was concentrated under high vacuum and the residue was purified by preparative reverse phase HPLC on a C18 column using a NH4OAc buffered H2O/CH3CN gradient, and concentrated to give N-(1-(1,2,4-oxadiazol-3-yl)cyclobutyl)-2-methylpropane-2-sulfinamide (45 mg, 0.19 mmol, 14% yield) as a light brown oil consistent by LCMS. LC-MS retention time: 1.31 min; m/z (MH+): 244. 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 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. customhad been consumed
  2. concentrationThe reaction was concentrated under high vacuum
  3. customthe residue was purified by preparative reverse phase HPLC on a C18 column
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-67264e7630e144de9369b2a5c438f3ee
Source dataset
uspto-grants-2015_02
Patent number
US08962651B2

Reaction notes

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