Cesium fluoride → 6-Methyl-3-(2-pyrimidinyl)-2-pyridinecarbonitrile

HRID 1094758Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1094758
CC1(C)COB([C:8]2[C:9]([C:15]#[N:16])=[N:10][C:11]([CH3:14])=[CH:12][CH:13]=2)OC1.Br[C:19]1[N:24]=[CH:23][CH:22]=[CH:21][N:20]=1.[F-].[Cs+]>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.[Cu]I.O1CCOCC1>[CH3:14][C:11]1[N:10]=[C:9]([C:15]#[N:16])[C:8]([C:19]2[N:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:13][CH:12]=1

Komponenten

7

Edukt 3

HCID 25953Cesium fluorideHCID 783452-BromopyrimidineHCID 593637323-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-6-methyl-2-pyridinecarbonitrile

Produkt 1

HCID 593637436-Methyl-3-(2-pyrimidinyl)-2-pyridinecarbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

An alternative route to make D18 is: 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-6-methyl-2-pyridinecarbonitrile D17 (50.6 mg) was dissolved 1,4-Dioxane (1 ml) under nitrogen in a vial, then 2-bromopyrimidine (42.0 mg, 0.264 mmol), CsF (67 mg, 0.441 mmol), Pd(Ph3P)4 (12 mg, 10.38 μmol) and CuI (7 mg, 0.037 mmol) were added in sequence. The vial was then capped and stirred at 65° C., after 1 hour the solvent was removed at reduced pressure and the residue partitioned between AcOEt (10 mls) and NaHCO3 (saturated solution, 10 ml). The phases were separated and the water was extracted with AcOEt (2×10 mls). The organic fraction were joined together, dried over Na2SO4 and evaporated at reduced pressure, obtaining an orange oily residue which was purified (Biotage, Snap 25 g silica gel column, AcOEt/Cy from pure Cy to 50:50 in 10 column volumes) to obtain the title compound D18 as pale yellow solid (27.6 mg).

Aufarbeitung

  1. additionwere added in sequence
  2. customThe vial was then capped
  3. customwas removed at reduced pressure
  4. customthe residue partitioned between AcOEt (10 mls) and NaHCO3 (saturated solution, 10 ml)
  5. customThe phases were separated
  6. extractionthe water was extracted with AcOEt (2×10 mls)
  7. dry with materialdried over Na2SO4
  8. customevaporated at reduced pressure
  9. customobtaining an orange oily residue which
  10. customwas purified (Biotage, Snap 25 g silica gel column, AcOEt/Cy from pure Cy to 50:50 in 10 column volumes)

Quellen und Nachweise

ORD-Eintrag
ord-811bd4e2c48b44559a7e26814be9fd4f
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08133908B2

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