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Hydrochloric Acid → N-(6-(4-cyanobutyl)pyridazin-3-yl)-2-phenylacetamide

HRID 1910469
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1910469
[Br-].[C:2]([CH2:4][CH2:5][CH2:6][CH2:7][Zn+])#[N:3].Cl[C:10]1[N:15]=[N:14][C:13]([NH:16][C:17](=[O:25])[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:12][CH:11]=1.Cl>CCOC(C)=O.Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1>[C:2]([CH2:4][CH2:5][CH2:6][CH2:7][C:10]1[N:15]=[N:14][C:13]([NH:16][C:17](=[O:25])[CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:12][CH:11]=1)#[N:3]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 313Hydrochloric AcidHCID 86687867N-(6-chloropyridazin-3-yl)-2-phenylacetamideHCID 178510995HCID 178510995, Verbindung

Produkt 1

HCID 86687868N-(6-(4-cyanobutyl)pyridazin-3-yl)-2-phenylacetamideAusbeute 60,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418745HCID 178418745, Verbindung
Katalysator
HCID 8857Ethyl AcetateLösungsmittel2×

Reaktionsbedingungen

Temperatur
19 °C

Versuchsvorschrift

A 1000 mL three-neck flask fitted with internal temperature probe and addition funnel was flushed with Ar(g). Under positive Argon pressure 4-cyanobutylzinc bromide (0.5M in THF, 500 mL, 250 mmol) was charged into the addition funnel then added to the reaction vessel at room temperature. Solid N-(6-chloropyridazin-3-yl)-2-phenylacetamide (20.6 g, 83.3 mmol) was added to the stirred solution at RT under Ar(g) flow, followed by the addition of NiCl2(dppp) (4.52 g, 8.33 mmol). The resulting mixture was stirred at 19° C. for 240 minutes and then quenched with ethanol (120 mL). Water (380 mL) added to the stirred red solution, giving a thick precipitate. Ethyl acetate (760 mL) added and stirred well for 30 minutes. The solids were removed by filtration through a pad of celite. The mother liquor was then transferred to a separatory funnel and the organic layer was washed with H2O (380 mL), 0.5% ethylenediaminetetraacetic acid solution (380 mL) and again with H2O (380 mL). The organic layer was concentrated by rotoevaporation. Resulting red oil was redissolved in EtOAc (200 mL) and 1M HCl (380 mL) was added to the well stirred flask. After 30 minutes the mixture was transferred to separatory funnel and the aqueous layer collected. The organic layer was extracted with 1M HCl (2×380 mL). The aqueous layer's pH was then adjusted to ˜7 using 7.5% sodium bicarbonate solution and the pale yellow precipitate was collected by suction filtration, rinsed with water (200 mL) and diethyl ether (2×200 mL). The solid was dried overnight under high vacuum to afford N-(6-(4-cyanobutyl)pyridazin-3-yl)-2-phenylacetamide (1023, 14.76 g). 1H NMR (300 MHz, DMSO-d6) δ 11.29 (s, 1H), 8.23 (d, J=9.036 Hz, 1H), 7.59 (d, J=9.246 Hz, 1H), 7.32 (m, 5H), 3.79 (s, 2H), 2.90 (t, J=7.357 Hz, 2H), 2.56 (t, J=7.038 Hz, 2H), 1.79 (t, J=7.311 Hz, 2H), 1.63 (t, J=7.01 Hz, 2H)

Aufarbeitung

  1. customA 1000 mL three-neck flask fitted with internal temperature probe and addition funnel
  2. customwas flushed with Ar(g)
  3. additionthen added to the reaction vessel at room temperature
  4. customquenched with ethanol (120 mL)
  5. additionWater (380 mL) added to the stirred red solution
  6. customgiving a thick precipitate
  7. stirringstirred well for 30 minutes
  8. customThe solids were removed by filtration through a pad of celite
  9. customThe mother liquor was then transferred to a separatory funnel
  10. washthe organic layer was washed with H2O (380 mL), 0.5% ethylenediaminetetraacetic acid solution (380 mL) and again with H2O (380 mL)
  11. concentrationThe organic layer was concentrated by rotoevaporation
  12. customResulting red oil
  13. stirringstirred flask
  14. waitAfter 30 minutes the mixture was transferred to separatory funnel
  15. customthe aqueous layer collected
  16. extractionThe organic layer was extracted with 1M HCl (2×380 mL)
  17. filtrationthe pale yellow precipitate was collected by suction filtration
  18. washrinsed with water (200 mL) and diethyl ether (2×200 mL)
  19. customThe solid was dried overnight under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-80bd102d3a7c4093a4dd50eec40b8eff
Quelldatensatz
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08604016B2

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