Water → N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-2-cyclohexylacetamide

HRID 626545Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 626545
[CH:1]1([CH2:7][C:8]([NH2:10])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)[C:12](Cl)=[O:13].[NH2:17][C:18]1[N:23]=[CH:22][C:21]([O:24][C:25]2[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32](=[O:34])[CH3:33])[CH:26]=2)=[CH:20][CH:19]=1.O>ClCCCl.C1COCC1>[C:32]([NH:31][C:27]1[CH:26]=[C:25]([O:24][C:21]2[CH:20]=[CH:19][C:18]([NH:17][C:12]([NH:10][C:8](=[O:9])[CH2:7][CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[O:13])=[N:23][CH:22]=2)[CH:30]=[CH:29][N:28]=1)(=[O:34])[CH3:33]

Komponenten

7

Edukt 4

HCID 962WaterHCID 65578Oxalyl chlorideHCID 95078CyclohexaneacetamideHCID 90410482N-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)acetamide

Produkt 1

HCID 86272276N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-2-cyclohexylacetamideAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A solution 2-cyclohexylacetamide (0.104 g, 0.737 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.129 mL, 1.474 mmol) and heated at 70° C. overnight. The mixture was concentrated to dryness, added to a solution of Example A2 (0.09 g, 0.368 mmol) and TEA (0.154 mL, 1.105 mmol) in THF (3 mL) and stirred at RT for 1 h. The mixture was treated with water, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness. The resulting residue was suspended in 60% EtOAc/Hex, sonicated and the solid collected via filtration and dried to afford N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-2-cyclohexylacetamide (77 mg, 51%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.11 (s, 1H), 10.83 (s, 1H), 10.56 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.18 (d, J=5.7 Hz, 1H), 8.07 (d, J=9.0 Hz, 1H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 6.68 (dd, J=5.7, 2.4 Hz, 1H), 2.27 (d, J=7.0 Hz, 2H), 2.02 (s, 3H), 1.73-1.56 (br m, 5H), 1.18-1.13 (m, 4H), 0.97-0.94 (m, 2H); MS (ESI) m/z: 412.2 (M+H+).

Aufarbeitung

  1. concentrationThe mixture was concentrated to dryness
  2. extractionextracted with EtOAc (2×)
  3. washthe combined organics were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to dryness
  6. customsonicated
  7. filtrationthe solid collected via filtration
  8. customdried

Quellen und Nachweise

ORD-Eintrag
ord-113b6ca5b8224cc9b141eb8a07757e11
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09309224B2

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