P-Toluenesulfonylhydrazide → HCID 45110122, compound

HRID 386908Notes

Reaction equation

HRID 386908 reaction equation
[CH3:1][C:2]([C:6]1[CH:10]=[C:9]([NH:11][C:12](=[O:25])[C:13]([CH3:24])([S:15]([CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)(=[O:17])=[O:16])[CH3:14])[O:8][N:7]=1)([CH3:5])[CH:3]=[O:4].[C:26]1(C)C=CC=CC=1.C[Mg]Br.C1COCC1.S(NN)(C1C=CC(C)=CC=1)(=O)=O>C(Cl)Cl>[OH:4][CH:3]([CH3:26])[C:2]([C:6]1[CH:10]=[C:9]([NH:11][C:12](=[O:25])[C:13]([CH3:24])([S:15]([CH:18]2[CH2:19][CH2:20][O:21][CH2:22][CH2:23]2)(=[O:17])=[O:16])[CH3:14])[O:8][N:7]=1)([CH3:1])[CH3:5]

Participants

5

Reactant 3

HCID 15303P-ToluenesulfonylhydrazideHCID 59253148HCID 59253148, compoundHCID 178420637HCID 178420637, compound2×

Product 1

HCID 45110122HCID 45110122, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
3 °C

Procedure

To a cooled (−20° C.) solution of N-[3-(1,1-Dimethyl-2-oxo-ethyl)-isoxazol-5-yl]-2-methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionamide (792 mg, 2.13 mmol) in DCM (16 mL) is added dropwise 1.4 M methylmagnesium bromide toluene/THF solution (75:25) over 10 minutes. DCM (7 mL) is added after ⅓ of the addition of 1.4 M methylmagnesium bromide toluene/THF solution. After the addition, the reaction mixture is stirred in a cold bath and slowly warmed up to 3° C. after 30 minutes. After this time, the reaction mixture is quenched with saturated aqueous NH4Cl solution and extracted with ethyl acetate twice. The organics are combined and washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The solids are dissolved in DCM (30 mL) and PS-TsNHNH2 (200 mg, 0.55 mmol) is added and the mixture is placed on a shaker for 1 h. After this time, the reaction mixture is filtered and the filtrate is concentrated under reduced pressure. Purification by preparative HPLC affords the title compound. Yield: 80%; m/z 389 [M+H].

Workup

  1. additionAfter the addition
  2. customAfter this time, the reaction mixture is quenched with saturated aqueous NH4Cl solution
  3. extractionextracted with ethyl acetate twice
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe solids are dissolved in DCM (30 mL)
  9. filtrationAfter this time, the reaction mixture is filtered
  10. concentrationthe filtrate is concentrated under reduced pressure
  11. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-236b54b6fc89468a86bb9510268eccf5
Source dataset
uspto-grants-2013_02
Patent number
US08372874B2

Reaction notes

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