Water → N-[6-(6-Fluoro-1H-indol-4-yl)-1H-indazol-4-yl]-1-(1-methylethyl)-1H-pyrazole-5-carboxamide

HRID 244747Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 244747
P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:10]1[CH:18]=[C:17]([F:19])[CH:16]=[C:15]2[C:11]=1[CH:12]=[CH:13][NH:14]2.[CH3:20][CH:21]([N:23]1[C:27]([C:28]([NH:30][C:31]2[C:32]3[C:36]([CH:37]=[C:38](B4OC(C)(C)CC(C)(C)O4)[CH:39]=2)=[N:35][N:34](C2CCCCO2)[CH:33]=3)=[O:29])=[CH:26][CH:25]=[N:24]1)[CH3:22].O>O1CCOCC1.CO>[F:19][C:17]1[CH:16]=[C:15]2[C:11]([CH:12]=[CH:13][NH:14]2)=[C:10]([C:38]2[CH:37]=[C:36]3[C:32]([CH:33]=[N:34][NH:35]3)=[C:31]([NH:30][C:28]([C:27]3[N:23]([CH:21]([CH3:22])[CH3:20])[N:24]=[CH:25][CH:26]=3)=[O:29])[CH:39]=2)[CH:18]=1

Komponenten

7

Edukt 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 247281734-Bromo-6-fluoro-1H-indoleHCID 582557371-(1-Methylethyl)-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1H-pyrazole-5-carboxamide

Produkt 1

HCID 58356321N-[6-(6-Fluoro-1H-indol-4-yl)-1H-indazol-4-yl]-1-(1-methylethyl)-1H-pyrazole-5-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A microwave vial was charged with Solvias catalyst (8 mg), tripotassium phosphate (90 mg) and 4-bromo-6-fluoro-1H-indole (available from Sinova, 33 mg). 1-(1-Methylethyl)-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1H-pyrazole-5-carboxamide (70 mg) in 1,4-dioxane (0.5 ml) was added followed by water (0.1 ml). The mixture was heated under microwave irradiation at 120° C. for 10 min. The mixture was passed through a silica cartridge which had been preconditioned with methanol, washed through with methanol, then dried under a stream of nitrogen. The residue was subjected to a DCM/water wash and then dried under a stream of nitrogen. The residue was dissolved in DMSO:methanol (1 ml, 1:1, v/v) and purified by MDAP (method A). Appropriate fractions were evaporated under a stream of nitrogen. The residues were dissolved in a minimum amount of methanol, a few drops of 2M HCl (aq) were added and the reactions were left to stand briefly at room temperature. The reactions were combined then passed through an aminopropyl cartridge preconditioned with methanol and dried. Purification was carried out using the following system:

Aufarbeitung

  1. washwashed through with methanol
  2. customdried under a stream of nitrogen
  3. washwash
  4. customdried under a stream of nitrogen
  5. dissolutionThe residue was dissolved in DMSO
  6. custommethanol (1 ml, 1:1, v/v) and purified by MDAP (method A)
  7. customAppropriate fractions were evaporated under a stream of nitrogen
  8. dissolutionThe residues were dissolved in a minimum amount of methanol, a few drops of 2M HCl (aq)
  9. additionwere added
  10. waitthe reactions were left
  11. customto stand briefly at room temperature
  12. customdried
  13. customPurification

Quellen und Nachweise

ORD-Eintrag
ord-088088498f9e4486a80a75ca4c3945b9
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658635B2

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