Hexamethylditin → 2-[6-(7-Trifluoromethyl[1,8]naphthyridin-4-yl)pyridin-2-yl]benzonitrile

HRID 1061830

Reaktionsgleichung

Reaktionsgleichung von HRID 1061830
Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]([F:15])([F:14])[F:13])=[N:7]2.C[Sn](C)C.C[Sn](C)C.Br[C:25]1[N:30]=[C:29]([C:31]2[CH:38]=[CH:37][CH:36]=[CH:35][C:32]=2[C:33]#[N:34])[CH:28]=[CH:27][CH:26]=1>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:13][C:12]([F:15])([F:14])[C:6]1[N:7]=[C:8]2[C:3]([C:2]([C:25]3[N:30]=[C:29]([C:31]4[CH:38]=[CH:37][CH:36]=[CH:35][C:32]=4[C:33]#[N:34])[CH:28]=[CH:27][CH:26]=3)=[CH:11][CH:10]=[N:9]2)=[CH:4][CH:5]=1

Komponenten

6

Edukt 3

HCID 6327618HexamethylditinHCID 221807852-(6-Bromopyridin-2-yl)benzonitrileHCID 222852765-chloro-2-(trifluoromethyl)-1,8-Naphthyridine

Produkt 1

HCID 101100422-[6-(7-Trifluoromethyl[1,8]naphthyridin-4-yl)pyridin-2-yl]benzonitrile

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysator2×HCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 5-Chloro-2-trifluoromethyl[1,8]naphthyridine (200 mg, 0.86 mmol) and hexamethylditin (178 μL, 282 mg, 0.86 mmol) in DME (5 mL) was degassed via three “freeze-thaw” cycles. Tetrakis(triphenylphosphine)palladium(0) (49.7 mg, 0.043 mmol) was added, and the mixture was degassed as before, then was heated under nitrogen at 80° C. overnight. 2-(6-Bromopyridin-2-yl)benzonitrile (126 mg, 0.48 mmol) was added and the mixture was degassed as before, then more tetrakis(triphenylphosphine)palladium(0) (49.7 mg, 0.043 mmol) was added, the mixture was degassed again, then was stirred at 80° C. under nitrogen overnight. Water (25 mL) and dichloromethane (15 mL) were added to the cooled mixture, and the aqueous layer was washed with more dichloromethane (2×15 mL). The combined organic layers were washed with saturated sodium chloride solution (1×25 mL) then were dried over magnesium sulfate and concentrated in vacuo. The residual material was purified by flash chromatography on silica gel, eluting with 10% to 40% ethyl acetate in dichloromethane, affording 2-[6-(7-trifluoromethyl[1,8]naphthyridin-4-yl)pyridin-2-yl]benzonitrile as a colourless solid, which was recrystallised from ethyl acetate/isohexane (44 mg, 24%). δH (400 MHz, CDCl3) 7.52-7.60 (1H, td, J 7.6 and 1.2), 7.71-7.77 (2H, m), 7.82 7.92 (5H, m), 8.12 (1H, t, J 7.8), 9.11 (1H, d, J 8.6), 9.35 (1H, d, J 4.3). m/z (ES+) 377 [MH]+.

Aufarbeitung

  1. customwas degassed via three “freeze-thaw” cycles
  2. customthe mixture was degassed as before,
  3. additionwas added
  4. customthe mixture was degassed again
  5. additionWater (25 mL) and dichloromethane (15 mL) were added to the cooled mixture
  6. washthe aqueous layer was washed with more dichloromethane (2×15 mL)
  7. washThe combined organic layers were washed with saturated sodium chloride solution (1×25 mL)
  8. dry with materialthen were dried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe residual material was purified by flash chromatography on silica gel
  11. washeluting with 10% to 40% ethyl acetate in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-057b9cc1b7af4f0ba5b329db31c811bd
Quelldatensatz
uspto-grants-2005_11
Patentnummer
US06960598B2

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