2-Chloro-6-(tributylstannyl)pyrazine → 3-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1529375Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1529375
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[N:15]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:14]=[C:13]4I)[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1.[Cl:26][C:27]1[CH:32]=[N:31][CH:30]=[C:29]([Sn](CCCC)(CCCC)CCCC)[N:28]=1>CN(C=O)C.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>[Cl:26][C:27]1[N:28]=[C:29]([C:13]2[C:12]3[C:16](=[CH:17][CH:18]=[C:10]([C:8]4[CH:7]=[N:6][CH:5]=[C:4]([CH:1]5[CH2:3][CH2:2]5)[N:9]=4)[CH:11]=3)[N:15]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:14]=2)[CH:30]=[N:31][CH:32]=1

Komponenten

6

Edukt 2

HCID 117740572-Chloro-6-(tributylstannyl)pyrazineHCID 679600395-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Produkt 1

HCID 867097793-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleAusbeute 35,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

A glass microwave reaction vessel was charged with 5-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (140 mg, 0.31 mmol), 2-chloro-6-(tributylstannyl)pyrazine (190 mg, 0.47 mmol), Pd(PPh3)4 (18 mg, 0.016 mmol) and CuI (6 mg, 0.031 mmol) in DMF (1 mL). Argon was bubbled through the mixture for 5 min. The tube was sealed and the mixture was heated to 105° C. for 2 h. The reaction was diluted with EtOAc and water and filtered through celite. The crude was purified by silica gel chromatography, eluting with a gradient of 0-50% EtOAc in hexanes, to provide 3-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (48 mg, 0.11 mmol, 35% yield) as a light-yellow solid. MS (ESI, pos. ion) m/z: 433.0 (M+1).

Aufarbeitung

  1. customA glass microwave reaction vessel
  2. customArgon was bubbled through the mixture for 5 min
  3. customThe tube was sealed
  4. additionThe reaction was diluted with EtOAc and water
  5. filtrationfiltered through celite
  6. customThe crude was purified by silica gel chromatography
  7. washeluting with a gradient of 0-50% EtOAc in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-7be510b86e5248bd92a2b5832f49840a
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090593B2

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