2-Methoxyethylamine → HCID 86275387, compound

HRID 626598Notes

Reaction equation

HRID 626598 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:29])OC(C)=C)[CH:18]=2)=[CH:12][CH:11]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[CH3:31][O:32][CH2:33][CH2:34][NH2:35].CN1CCCC1>O1CCOCC1.CC#N.O>[CH3:31][O:32][CH2:33][CH2:34][NH:35][C:24](=[O:29])[NH:23][C:19]1[CH:18]=[C:17]([O:16][C:13]2[CH:12]=[CH:11][C:10]([NH:9][C:8]([NH:7][C:1](=[O:6])[C:2]([CH3:5])([CH3:3])[CH3:4])=[O:30])=[N:15][CH:14]=2)[CH:22]=[CH:21][N:20]=1

Participants

6

Reactant 3

HCID 80182-MethoxyethylamineHCID 84541-MethylpyrrolidineHCID 90445670Prop-1-en-2-yl (4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)carbamate

Product 1

HCID 86275387HCID 86275387, compoundYield 43.3%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of Example C2 (0.120 g, 0.290 mmol), 2-methoxyethylamine (0.1 mL, 1.15 mmol) and N-methylpyrrolidine (0.012 g, 0.145 mmol) in dioxane (5 mL) was heated at 80° C. overnight, cooled to RT, and concentrated to dryness. The residue was dissolved in DCM and stirred with sat'd NaHCO3. 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 white solid, which was dissolved in MeCN/H2O, frozen and lypholized overnight to afford N-((5-((2-(3-(2-methoxyethyl)ureido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide as a white solid (54 mg, 43%). 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.44 (s, 1H), 9.14 (s, 1H), 8.24 (d, J=2.9 Hz, 1H), 8.07-8.06 (m, 2H), 7.96 (s, 1H), 7.72 (dd, J=9.0, 2.9 Hz, 1H), 6.97 (d, J=2.3 Hz, 1H), 6.57 (dd, J=5.9, 2.4 Hz, 1H), 3.35-3.34 (m, 2H), 3.28-3.22 (m, 2H), 3.24 (s, 3H), 1.21 (s, 9H); MS (ESI) m/z: 431.2 (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 white solid, which
  9. temperaturefrozen

Sources & evidence

ORD record
ord-95d2ef12a4214be7a0bfcd259b29daca
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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