Cesium fluoride → tert-Butyl (1S,3R)-3-(6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yloxy)cyclohexylcarbamate

HRID 1775104Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1775104
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:15]([Sn](C)(C)C)=[N:14][N:13]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:10]3=[CH:11][N:12]=2)[CH:2]=1.Br[C:29]1[N:34]=[C:33]([O:35][C@@H:36]2[CH2:41][CH2:40][CH2:39][C@H:38]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[CH2:37]2)[CH:32]=[CH:31][CH:30]=1.[F-].[Cs+]>CN(C)C=O.O.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>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:15]([C:29]4[N:34]=[C:33]([O:35][C@@H:36]5[CH2:41][CH2:40][CH2:39][C@H:38]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:47])([CH3:46])[CH3:48])[CH2:37]5)[CH:32]=[CH:31][CH:30]=4)=[N:14][N:13]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:10]3=[CH:11][N:12]=2)[CH:2]=1

Komponenten

8

Edukt 3

HCID 25953Cesium fluorideHCID 71253848HCID 71253848, VerbindungHCID 86676699tert-Butyl (1S,3R)-3-(6-bromopyridin-2-yloxy)cyclohexylcarbamate

Produkt 1

HCID 86676700tert-Butyl (1S,3R)-3-(6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yloxy)cyclohexylcarbamateAusbeute 53 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A mixture of 147 mg (0.3 mmol) of 5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-3-(trimethylstannyl)-1H-pyrazolo[3,4-c]pyridine, 123 mg, 0.33 mmol) of tert-butyl (1S,3R)-3-(6-bromopyridin-2-yloxy)cyclohexylcarbamate, 109 mg (0.72 mmol) of Cesium fluoride, 35 mg (0.03 mmol) of tetrakis(triphenylphosphine)palladium(0) and 11.4 mg (0.06 mmol) of copper(I) iodide in 2 ml of N,N-dimethylformamide was heated at 50° C. for 2 hours in a Stille coupling. The mixture was diluted with water and extracted with ethyl acetate. The organic extracts were washed with water, brine, dried over MgSO4 and concentrated. The residue was purified via silica gel chromatography using a gradient of ethyl acetate in heptane to afford 98 mg (53%) of tert-Butyl (1S,3R)-3-(6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yloxy)cyclohexylcarbamate. ESI MS m/z 617.5 (M+1).

Aufarbeitung

  1. extractionextracted with ethyl acetate
  2. washThe organic extracts were washed with water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-cd387be5ea374d3e819c28f026b2e1d8
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09260425B2

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