Pyridine → HCID 68874736, compound

HRID 490218Notes

Reaction equation

HRID 490218 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CS(Cl)(=O)=[O:9].[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.C(N(CC)[CH:28]([CH3:30])[CH3:29])(C)C.[C:33](OCC)(=O)[CH3:34]>ClCCl>[CH3:2][C:3]1[CH:4]=[C:5]([CH:30]=[CH:28][CH:29]=1)[C:6]([NH:1][CH2:33][CH2:34][N:21]1[CH2:20][CH2:19][N:18]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][N:12]=2)[CH2:23][CH2:22]1)=[O:9]

Participants

7

Reactant 5

HCID 1049PyridineHCID 8857Ethyl AcetateHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 944591-(2-Pyridyl)piperazine

Product 1

HCID 68874736HCID 68874736, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the resulting alcohol (55 mg, 0.31 mmol) and pyridine (33 μL, 0.37 mmol) in dichloromethane (0.5 mL) at 0° C. was added methanesulfonyl chloride (43 mg, 0.37 mmol). After 1 hour at room temperature, the mixture was diluted with 10 mL ethyl acetate. The organic layer was washed with 2× dilute aqueous ammonium chloride (5 mL), 2× brine (5 mL), dried over magnesium sulfate, filtered and evaporated. The residue was dissolved in N,N-dimethylformamide (1 mL) and treated with 1-pyridin-2-ylpiperazine (48 μL, 0.31 mmol) and N,N-diisopropylethylamine (155 μL, 0.78 mmol). After 24 hours at 100° C., the mixture was cooled and concentrated. The residue was purified by flash column chromatography on silica gel (elution with 1-2.5% methanol:dichloromethane) to provide 45 mg (45% yield) of the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ 2.40 (s, 3H), 2.66 (m, 6H), 3.60 (m, 6H), 6.65 (m, 2H), 6.84 (s, 1H), 7.31 (m, 2H), 7.49 (ddd, J=8.7, 7.0, 2.0 Hz, 1H), 7.55 (m, 1H), 7.63 (s, 1H), 8.20 (ddd, J=5.0, 2.0, 0.9 Hz, 1H); MS (DCI/NH3) m/e 325 (M+H)+; Anal. calcd for C19H24N4O.0.2 H2O: C, 69.57; H, 7.50; N, 17.08. Found: C, 69.41; H, 7.21; N, 17.10.

Workup

  1. washThe organic layer was washed with 2× dilute aqueous ammonium chloride (5 mL), 2× brine (5 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. dissolutionThe residue was dissolved in N,N-dimethylformamide (1 mL)
  6. waitAfter 24 hours at 100° C.
  7. temperaturethe mixture was cooled
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography on silica gel (elution with 1-2.5% methanol:dichloromethane)

Sources & evidence

ORD record
ord-7a3b3db7099543a3b176e3a0b91337c0
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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