Ethyl Acetate → N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(tetrahydro-2H-pyran-4-yl)-6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 1909217Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1909217
Br[C:2]1[CH:3]=[C:4]([C:17]([NH:19][CH2:20][C:21]2[C:22](=[O:29])[NH:23][C:24]([CH3:28])=[CH:25][C:26]=2[CH3:27])=[O:18])[C:5]2[CH:10]=[N:9][N:8]([CH:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[C:6]=2[N:7]=1.[CH3:30][C:31]1([CH3:48])[CH2:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][C:33]([CH3:47])([CH3:46])[NH:32]1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>O1CCOCC1.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>[CH3:27][C:26]1[CH:25]=[C:24]([CH3:28])[NH:23][C:22](=[O:29])[C:21]=1[CH2:20][NH:19][C:17]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[C:6]=2[N:7]=[C:2]([C:35]2[CH2:34][C:33]([CH3:47])([CH3:46])[NH:32][C:31]([CH3:48])([CH3:30])[CH:36]=2)[CH:3]=1)=[O:18]

Komponenten

7

Edukt 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 467380232,2,6,6-Tetramethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridineHCID 867034166-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Produkt 1

HCID 68350876N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(tetrahydro-2H-pyran-4-yl)-6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamideAusbeute 14 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of 6-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (1 equiv.), 2,2,6,6-tetramethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (1.2 equiv.) and Pd(PPh3)4 (0.1 equiv.) in 1,4-dioxane was purged with argon for 10 min. Then, 2 M Na2CO3 (3.6 equiv.) solution was added to it and again argon was purged through it for 10 min. The reaction mixture was stirred at 100° C. for 1 h. After completion of the reaction, water was added to it and extraction was carried out using EtOAc. The combined organic layers were washed with water, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford crude material which was purified by column chromatography to give the desired compound (14%). LCMS: 519.30 (M+1)+; HPLC: 98.464% (@ 254 nm) (Rt; 4.823); 1H NMR (DMSO-d6, 400 MHz) δ 11.55 (bs, 1H); 8.87 (s, 1H); 8.30 (s, 1H); 7.82 (s, 1H); 6.81 (s, 1H); 5.90 (s, 1H); 5.06 (m, 1H); 4.38 (s, 2H); 3.01 (d, J=11.2, 2H); 3.59 (t, J=12.0 Hz, 2H); 2.23 (s, 3H); 2.23-2.19 (m, 2H); 2.12 (s, 3H); 1.90 (d, J=12.0 Hz, 2H); 1.27-1.23 (m, 14H).

Aufarbeitung

  1. customwas purged through it for 10 min
  2. customAfter completion of the reaction, water
  3. additionwas added to it and extraction
  4. washThe combined organic layers were washed with water
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto afford crude material which
  9. customwas purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-282e6da113b84d16b820826a2f041b4c
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08598167B1

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