Trimethylsilylacetylene → 6'-((Trimethylsilyl)ethynyl)-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4']bipyridinyl-3'-ylamine

HRID 1506067Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1506067
Br[C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:28])=[N:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:17][CH:16]=3)[CH:14]=2)[CH:3]=1.C(N(CC)C(C)C)(C)C.[CH3:38][Si:39]([C:42]#[CH:43])([CH3:41])[CH3:40]>O1CCOCC1.C(Cl)Cl.CO.[Cu]I.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>[CH3:38][Si:39]([C:42]#[C:43][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:28])=[N:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:17][CH:16]=3)[CH:14]=2)[CH:3]=1)([CH3:41])[CH3:40]

Komponenten

9

Edukt 3

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 582666266'-Bromo-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4]bipyridinyl-3'-ylamine

Produkt 1

HCID 582665496'-((Trimethylsilyl)ethynyl)-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4']bipyridinyl-3'-ylamine

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 6′-bromo-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4′]bipyridinyl-3′-ylamine (100 mg, 0.23 mmol), copper (I) iodide (4.3 mg, 0.02 mmol), and N,N-diisopropylethylamine (0.08 mL, 0.45 mmol) in anhydrous 1,4-dioxane (2.5 mL) was degassed and flushed with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (26 mg, 0.02 mmol) and (trimethylsilyl)acetylene (0.16 mL, 1:1 mmol) were added and the reaction was heated at 100° C. for 5 h. The cooled reaction mixture was diluted with DCM (20 mL) and methanol (2 mL) and washed with water (15 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromotagraphy (silica, 10 g column, Biotage, 0-10% methanol in (DCM containing 1% 7M ammonia in ammonia)) to afford a brown residue that was taken to the next step without further purification.

Aufarbeitung

  1. customwas degassed
  2. customflushed with nitrogen
  3. customThe cooled reaction mixture
  4. washwashed with water (15 mL)
  5. customThe organic phase was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto afford a residue that
  10. customwas purified by flash chromotagraphy (silica, 10 g column, Biotage, 0-10% methanol in (DCM containing 1% 7M ammonia in ammonia))
  11. customto afford a brown residue that
  12. customwas taken to the next step without further purification

Quellen und Nachweise

ORD-Eintrag
ord-d7330a0eefc74e8fb8431e616e218e49
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09216980B2

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