Water → 2-Ethyl-4-[6-(4-hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-2,5,5-trimethyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 2279120Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2279120
[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12]([CH3:15])([CH3:14])[N:11]([CH2:16][C:17]2[CH:22]=[C:21](Br)[N:20]=[C:19]3[N:24]([CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][O:29]4)[N:25]=[C:26]([CH3:27])[C:18]=23)[CH2:10][C:9]1([CH2:35][CH3:36])[CH3:34])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:37][C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1.C(=O)([O-])[O-].[K+].[K+].O>COCCOC.O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12]([CH3:15])([CH3:14])[N:11]([CH2:16][C:17]2[CH:22]=[C:21]([C:41]3[CH:42]=[CH:43][C:38]([OH:37])=[CH:39][CH:40]=3)[N:20]=[C:19]3[N:24]([CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][O:29]4)[N:25]=[C:26]([CH3:27])[C:18]=23)[CH2:10][C:9]1([CH2:35][CH3:36])[CH3:34])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 900134844-[6-Bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-2-ethyl-2,5,5-trimethyl-piperazine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 1366232192-Ethyl-4-[6-(4-hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-2,5,5-trimethyl-piperazine-1-carboxylic acid tert-butyl esterAusbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 18180031Water 1,2-dimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a degassed mixture of 70 mg 4-[6-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-2-ethyl-2,5,5-trimethyl-piperazine-1-carboxylic acid tert-butyl ester, 21 mg 4-hydroxyphenylboronic acid and 19 mg potassium carbonate in DME/water (v/v=2/1, 0.7 mL) at r.t. and under Ar-atmosphere 2 mg palladium(0) bis(tri-tert-butylphosphine) was added and the mixture was stirred at 85° C. for 75 min in a microwave reactor. To the mixture water and ethyl acetate were added, the phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were concentrated in vacuo and the resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate). 19 mg (27%) of the title compound were obtained.

Aufarbeitung

  1. additionunder Ar-atmosphere 2 mg palladium(0) bis(tri-tert-butylphosphine) was added
  2. customthe phases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate
  4. concentrationThe combined organic phases were concentrated in vacuo
  5. customthe resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-dfada8d87f204f3b89a077c4e44a22a6
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133181B2

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