Tert-Butylamine → 5-(6-Hydroxymethylpyridin-2-yl)-1-(4-methylpiperazin-1-yl)pent-4-yn-1-one

HRID 1668535

Reaction equation

HRID 1668535 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][OH:9])[N:3]=1.[CH3:10][N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:22])[CH2:18][CH2:19][C:20]#[CH:21])[CH2:13][CH2:12]1.C(N)(C)(C)C>[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[OH:9][CH2:8][C:4]1[N:3]=[C:2]([C:21]#[C:20][CH2:19][CH2:18][C:17]([N:14]2[CH2:15][CH2:16][N:11]([CH3:10])[CH2:12][CH2:13]2)=[O:22])[CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 3

HCID 6385Tert-ButylamineHCID 3517811(6-Bromopyridin-2-yl)methanolHCID 577138121-(4-Methylpiperazin-1-yl)pent-4-yn-1-one

Product 1

HCID 595554265-(6-Hydroxymethylpyridin-2-yl)-1-(4-methylpiperazin-1-yl)pent-4-yn-1-oneYield 73%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a 50 mL round-bottom flask, 484 mg of 2-bromopyridine-6-methanol, 510 mg of 1-(4-methylpiperazin-1-yl)pent-4-yn-1-one, 20 mg of BHT, 162 mg of copper(I) iodide, 118 mg of tetrakis(triphenylphosphine)palladium (0), 375 mg of t-butylamine and 7.5 mL of DMF were added, and the mixture was stirred under argon atmosphere at 80° C. for 6 hours. The DMF was removed under reduced pressure, then saturated aqueous sodium bicarbonate was added thereto, and the mixture was extracted with chloroform. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and then the solvent was removed. The residue was purified by chromatography on silica gel (methylene chloride-methanol-triethylamine=600:20:1) to give 540 mg of 5-(6-hydroxymethylpyridin-2-yl)-1-(4-methylpiperazin-1-yl)pent-4-yn-1-one as a yellow oil.

Workup

  1. customThe DMF was removed under reduced pressure
  2. additionsaturated aqueous sodium bicarbonate was added
  3. extractionthe mixture was extracted with chloroform
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed
  7. customThe residue was purified by chromatography on silica gel (methylene chloride-methanol-triethylamine=600:20:1)

Sources & evidence

ORD record
ord-d2bdbbaf5ebd4324adf4133c98694e42
Source dataset
uspto-grants-2011_08
Patent number
US07989446B2

Linked notes

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