Ammonium Chloride → 6-Ethyl-5-[[2-(1-methyl-1h-pyrazol-4-yl)-4-pyridinyl]oxy]-2-pyridinamine

HRID 2278898Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2278898
[CH2:1]([C:3]1[C:8]([O:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([C:16]3[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=3)[CH:11]=2)=[CH:7][CH:6]=[C:5]([N+:22]([O-])=O)[N:4]=1)[CH3:2].[NH4+].[Cl-]>CO.C1COCC1.CCOC(C)=O.[Zn]>[CH2:1]([C:3]1[N:4]=[C:5]([NH2:22])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=2)[CH:11]=1)[CH3:2]

Komponenten

7

Edukt 2

HCID 25517Ammonium ChlorideHCID 904036202-Ethyl-3-[[2-(1-methyl-1h-pyrazol-4-yl)-4-pyridinyl]oxy]-6-nitropyridine

Produkt 1

HCID 904038036-Ethyl-5-[[2-(1-methyl-1h-pyrazol-4-yl)-4-pyridinyl]oxy]-2-pyridinamineAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 23994ZincKatalysatorHCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of crude 2-ethyl-3-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)-6-nitropyridine (1.280 g, 3.93 mmol) in MeOH (15 mL) and THF (15 mL) was treated with NH4Cl (8.42 g, 157 mmol), cooled to 0° C., treated portion-wise with zinc dust (2.57 g, 39.3 mmol), warmed to RT as the cooling bath expired and stirred overnight. The mixture was diluted with EtOAc, the solids removed via filtration through diatomaceous earth, washed with warm 2:1 EtOAc/MeOH and the filtrate concentrated to dryness. The residue was treated with EtOAc, heated to reflux, cooled to RT and the solids removed via filtration. The filtrate was again treated with EtOAc, heated to reflux and the solid collected via hot filtration. The filtrate was concentrated to dryness, purified via silica gel chromatography (MeOH/EtOAc) and combined with the above-isolated solid to afford 6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-amine (929 mg, 80%). 1H NMR (400 MHz, DMSO-d6): δ 8.30 (d, J=5.8 Hz, 1 H), 8.22 (s, 1 H), 7.93 (s, 1 H), 7.18 (d, J=8.7 Hz, 1 H), 7.12 (d, J=2.4 Hz, 1 H), 6.51 (dd, J=5.7, 2.4 Hz, 1 H), 6.36 (d, J=8.7 Hz, 1 H), 5.97 (s, 2 H), 3.84-3.83 (m, 3 H), 2.39 (q, J=7.6 Hz, 2 H), 1.04 (t, J=7.5 Hz, 3 H); MS (ESI) m/z: 296.1 (M+H+).

Aufarbeitung

  1. temperaturewarmed to RT as the cooling bath
  2. customthe solids removed via filtration through diatomaceous earth
  3. washwashed
  4. temperaturewith warm 2:1 EtOAc/MeOH
  5. concentrationthe filtrate concentrated to dryness
  6. additionThe residue was treated with EtOAc
  7. temperatureheated
  8. temperatureto reflux
  9. temperaturecooled to RT
  10. customthe solids removed via filtration
  11. additionThe filtrate was again treated with EtOAc
  12. temperatureheated
  13. temperatureto reflux
  14. filtrationthe solid collected via hot filtration
  15. concentrationThe filtrate was concentrated to dryness
  16. custompurified via silica gel chromatography (MeOH/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-9efb80208d9e4da4a5b7182cda58a11c
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133183B2

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