1-Butyne, 3-chloro-3-methyl- → 1-[1,1-Dimethylethoxycarbonyl]-4-[3-(1,1-dimethylprop-2-ynylamino)-2-pyridinyl]piperazine

HRID 2293765Notes

Reaction equation

HRID 2293765 reaction equation
[CH3:1][C:2]([CH3:20])([O:4][C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[C:18]([NH2:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:9][CH2:8]1)=[O:6])[CH3:3].Cl[C:22]([CH3:26])([CH3:25])[C:23]#[CH:24]>CN(C)C=O.[Cu]>[CH3:3][C:2]([CH3:20])([O:4][C:5]([N:7]1[CH2:8][CH2:9][N:10]([C:13]2[C:18]([NH:19][C:22]([CH3:26])([CH3:25])[C:23]#[CH:24])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:11][CH2:12]1)=[O:6])[CH3:1]

Participants

5

Reactant 2

HCID 706791-Butyne, 3-chloro-3-methyl-HCID 2756375tert-Butyl 4-(3-aminopyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 214776701-[1,1-Dimethylethoxycarbonyl]-4-[3-(1,1-dimethylprop-2-ynylamino)-2-pyridinyl]piperazine

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of 1-[1,1-dimethylethoxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine (International Publication No. WO 88/08424, 5.40 g), cuprous chloride (1.00 g), copper powder (1.00 g), and dry dimethylformamide (25 ml) under nitrogen at 0° is added a solution of 3-chloro-3-methyl-1-butyne (2.00 g) in dry dimethylformamide (5 ml) in 4 portions over 15 min. The resulting mixture is then stirred at 20°-25° for 16 hrs, concentrated, and diluted with methylene chloride (75 ml) and water (20 ml). The layers are separated and the aqueous phase is extracted with methylene chloride (25 ml). The combined organic phase is washed with saline (20 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a residue which is chromatographed on silica gel (70-230 mesh, 500 g), eluting with a gradient of ethyl acetate/hexane (10/90-20/80). Pooling of fractions giving an Rf =0.31 (ethyl acetate/hexane, 25/75) and removal of solvent under reduced pressure gives the title compound, NMR (CDCl3) 7.75, 7.47, 6.94, 4.61, 3.56, 3.00, 2.39, 1.64 and 1.48 δ.

Workup

  1. concentrationconcentrated
  2. additiondiluted with methylene chloride (75 ml) and water (20 ml)
  3. customThe layers are separated
  4. extractionthe aqueous phase is extracted with methylene chloride (25 ml)
  5. washThe combined organic phase is washed with saline (20 ml)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto give a residue which
  9. customis chromatographed on silica gel (70-230 mesh, 500 g)
  10. washeluting with a gradient of ethyl acetate/hexane (10/90-20/80)
  11. customPooling of fractions giving
  12. customan Rf =0.31 (ethyl acetate/hexane, 25/75) and removal of solvent under reduced pressure

Sources & evidence

ORD record
ord-c1f035efdef44dbb897c17d3c0195a10
Source dataset
uspto-grants-1997_11
Patent number
US05686610

Reaction notes

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