1-Methylpyrrolidine → HCID 86275152, compound

HRID 626596Notes

Reaction equation

HRID 626596 reaction equation
[C:1]([NH:7][C:8](=[O:30])[NH:9][C:10]1[N:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24](=O)[O:25]C(C)=C)[CH:18]=2)=[CH:12][CH:11]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[CH2:31]([N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)[CH3:32].CN1CCCC1>O1CCOCC1.CC#N.O>[CH2:31]([N:33]1[CH2:38][CH2:37][N:36]([C:24]([NH:23][C:19]2[CH:18]=[C:17]([O:16][C:13]3[CH:14]=[N:15][C:10]([NH:9][C:8]([NH:7][C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])=[O:30])=[CH:11][CH:12]=3)[CH:22]=[CH:21][N:20]=2)=[O:25])[CH2:35][CH2:34]1)[CH3:32]

Participants

6

Reactant 3

HCID 84541-MethylpyrrolidineHCID 791961-EthylpiperazineHCID 90445670Prop-1-en-2-yl (4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)carbamate

Product 1

HCID 86275152HCID 86275152, compoundYield 32.1%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A mixture of Example C2 (0.203 g, 0.491 mmol), N-ethyl piperazine (0.1 mL, 0.79 mmol) and N-methylpyrrolidine (0.021 g, 0.25 mmol) in dioxane (5 mL) was heated at 80° C. for 3 h, cooled to RT, and concentrated to dryness. The residue was dissolved in DCM and stirred with sat'd NaHCO3 for ˜15 min. The aqueous layer was back-extracted with DCM (3×) and the organic phases combined, dried (Na2SO4) and concentrated to afford a light brown oil. The crude residue was purified via silica gel chromatography (MeOH/DCM) to afford a colorless oil, which was suspended in MeCN/H2O, sonicated, frozen and lypholized overnight to afford 4-ethyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperazine-1-carboxamide as a white solid (74 mg, 32%). 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.44 (s, 1H), 9.25 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.12 (d, J=5.7 Hz, 1H), 8.08 (d, J=9.0 Hz, 1H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.37 (d, J=2.4 Hz, 1H), 6.61 (dd, J=5.7, 2.4 Hz, 1H), 3.44-3.35 (m, 4H), 2.35-2.23 (m, 6H), 1.21 (s, 9H), 0.98 (t, J=7.2 Hz, 3H); MS (ESI) m/z: 470.3 (M+H+).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in DCM
  3. extractionThe aqueous layer was back-extracted with DCM (3×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customto afford a light brown oil
  7. customThe crude residue was purified via silica gel chromatography (MeOH/DCM)
  8. customto afford a colorless oil, which
  9. customsonicated
  10. temperaturefrozen
  11. waitlypholized overnight

Sources & evidence

ORD record
ord-a5cc56c2f94c4f139700fee2851b27a0
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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