Water → 3-methyl-1-(tetrahydro-pyran-2-yl)-6-[4-(tetrahydro-pyran-2-yloxy)-phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester

HRID 2279095Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2279095
[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([CH3:16])=[N:14][N:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:8]=2[N:9]=[C:10](Br)[CH:11]=1)=[O:5])[CH3:2].[O:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[O:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+].O>COCCOC.O>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([CH3:16])=[N:14][N:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:8]=2[N:9]=[C:10]([C:33]2[CH:34]=[CH:35][C:30]([O:29][CH:24]3[CH2:25][CH2:26][CH2:27][CH2:28][O:23]3)=[CH:31][CH:32]=2)[CH:11]=1)=[O:5])[CH3:2]

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 50176524-(Tetrahydro-2H-pyran-2-yloxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 866803196-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester

Produkt 1

HCID 900142043-methyl-1-(tetrahydro-pyran-2-yl)-6-[4-(tetrahydro-pyran-2-yloxy)-phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl esterAusbeute 92,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 18180031Water 1,2-dimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a mixture of 6-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (6.00 g), 4-(tetrahydro-2H-pyran-2-yloxy)-phenylboronic acid (4.34 g) and potassium carbonate (2.93 g) in DME/water (v/v=2/1, 200 mL) was added at r.t. under Ar-atmosphere palladium(0) bis(tri-tert-butylphosphine) (0.42 g) and the mixture was stirred at 85° C. for 90 min. To the mixture water was added and it was extracted with ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate, and concentrated in vacuo. The resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate) to give 3-methyl-1-(tetrahydro-pyran-2-yl)-6-[4-(tetrahydro-pyran-2-yloxy)-phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (7.00 g, 92%). This material was dissolved in isopropanol (30 mL), and 1N sodium hydroxide solution (15 mL) was added. The solution was stirred overnight, then the mixture was contentrated in vacuo to about a third of its volume. The precipitated solid was isolated by filtration and dried in air giving the sodium salt of 3-methyl-1-(tetrahydro-pyran-2-yl)-6-[4-(tetrahydro-pyran-2-yloxy)-phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (6.2 g, 87%).

Aufarbeitung

  1. additionwas added at r.t. under Ar-atmosphere palladium(0) bis(tri-tert-butylphosphine) (0.42 g)
  2. extractionit was extracted with ethyl acetate
  3. washThe organic phase was washed with water
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-a68ca50c3c04413caededd8412e0ebbd
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133181B2

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