Sodium Carbonate → (Rac)-[6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-methanol

HRID 69192Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 69192
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:21]=[CH:20][C:19]4[C:15](=[CH:16][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[N:18]=4)[CH:14]=3)[OH:12])=[CH:9][N:10]=2)[N:7]=1.[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1.C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC>[CH3:30][N:31]1[CH:35]=[C:34]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([CH:11]([C:13]4[CH:21]=[CH:20][C:19]5[C:15](=[CH:16][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:28])([CH3:29])[CH3:27])[N:18]=5)[CH:14]=4)[OH:12])=[CH:9][N:10]=3)[N:7]=2)[CH:33]=[N:32]1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 87523362(Rac)-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-methanol

Produkt 1

HCID 68641096(Rac)-[6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-methanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

(rac)-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-[2-(2-trimethylsilanyl-ethoxymethyl)-2H-indazol-5-yl]-methanol (Stage 150.3, 134 mg, 0.296 mmol) was charged into a microwave vial together with DME (2 mL), 1-Methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H -pyrazole (173 mg, 0.815 mmol), followed by 2 M Na2CO3 (0.300 mL) and PdCl2(PPh3)2 (20 mg). The RM was submitted to microwave irradiation at 150° C. for 30 min. After filtration and evaporation of the solvent, the residue was taken into EtOAc and washed with saturated aqueous sodium carbonate. The aqueous phase was again extracted 3 times with EtOAc. Combined organic layers were washed with brine and dried on Na2SO4. After evaporation of the solvent the crude was purified by flash chromatography (CombiFlash® Companion System®, with 12 g RediSep® silica gel column, DCM/MeOH=100:0->92:8) to afford the title compound (tR 1.17 min (conditions 2), MH+=476)

Aufarbeitung

  1. customirradiation at 150° C. for 30 min
  2. filtrationAfter filtration and evaporation of the solvent
  3. washwashed with saturated aqueous sodium carbonate
  4. extractionThe aqueous phase was again extracted 3 times with EtOAc
  5. washCombined organic layers were washed with brine
  6. customdried on Na2SO4
  7. customAfter evaporation of the solvent the crude
  8. customwas purified by flash chromatography (CombiFlash® Companion System®, with 12 g RediSep® silica gel column, DCM/MeOH=100:0->92:8)

Quellen und Nachweise

ORD-Eintrag
ord-2807834d4a7f465a98cd174d33100564
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822468B2

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