Tert-butyl 4-((6-chloro-3-pyridinyl)sulfonyl)-2-oxo-1-piperazinecarboxylate → Tert-butyl (2-(((6-chloro-3-pyridinyl)sulfonyl)(2-oxo-3-pentyn-1-yl)amino)ethyl)carbamate

HRID 1972631Notes

Reaction equation

HRID 1972631 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:13](=[O:24])[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[C:25]([Mg]Br)#[C:26][CH3:27]>C1COCC1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([S:8]([N:11]([CH2:12][C:13](=[O:24])[C:25]#[C:26][CH3:27])[CH2:16][CH2:15][NH:14][C:17](=[O:18])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])(=[O:9])=[O:10])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 86670415Tert-butyl 4-((6-chloro-3-pyridinyl)sulfonyl)-2-oxo-1-piperazinecarboxylateHCID 178419101HCID 178419101, compound2×

Product 1

HCID 86670416Tert-butyl (2-(((6-chloro-3-pyridinyl)sulfonyl)(2-oxo-3-pentyn-1-yl)amino)ethyl)carbamateYield 81.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a slurry of tert-butyl 4-((6-chloro-3-pyridinyl)sulfonyl)-2-oxo-1-piperazinecarboxylate (1.16 g, 3.09 mmol) in THF (5.0 mL) at 0° C. was added a solution of prop-1-yn-1-ylmagnesium bromide (0.5 M in THF, 13 mL, 6.50 mmol, Sigma-Aldrich, St. Louis, Mo.). After 1.5 h at 0° C., additional prop-1-yn-1-ylmagnesium bromide (4 mL, 2.0 mmol) was added. After an additional 2.5 h at 0° C., the mixture was quenched with saturated aqueous NH4Cl (25 mL). EtOAc (40 mL) was added, the layers were separated, and the aqueous layer was extracted with EtOAc (10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated. The residue was purified by chromatography on silica gel using (30 to 90% EtOAc in hexanes) to give tert-butyl (2-(((6-chloro-3-pyridinyl)sulfonyl)(2-oxo-3-pentyn-1-yl)amino)ethyl)carbamate as a yellow powder (1.05 g)

Workup

  1. waitAfter an additional 2.5 h at 0° C.
  2. customthe mixture was quenched with saturated aqueous NH4Cl (25 mL)
  3. additionEtOAc (40 mL) was added
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (10 mL)
  6. dry with materialThe combined organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel using (30 to 90% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0aca447c853845cc942ef658893e290c
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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