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Sodium Carbonate → N-((4-ethyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 1909261
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1909261
Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:27])[NH:20][C:21]([CH3:26])=[CH:22][C:23]=2[CH2:24][CH3:25])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[CH3:28][C:29]1([CH3:46])[CH2:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][C:31]([CH3:45])([CH3:44])[NH:30]1.O1CCOCC1.O.C([O-])([O-])=O.[Na+].[Na+]>O.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>[CH2:24]([C:23]1[CH:22]=[C:21]([CH3:26])[NH:20][C:19](=[O:27])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([C:33]2[CH2:32][C:31]([CH3:45])([CH3:44])[NH:30][C:29]([CH3:46])([CH3:28])[CH:34]=2)[CH:3]=1)=[O:15])[CH3:25]
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Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 218864351,4-Dioxane--water (1/1)HCID 467380232,2,6,6-Tetramethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridineHCID 867034306-bromo-N-((4-ethyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Produkt 1

HCID 68295773
N-((4-ethyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide
Ausbeute 38 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a stirred solution of 6-bromo-N-((4-ethyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (0.37 g, 0.85 mmol) and 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.) in dioxane/water mixture (3 mL+1 mL for 1 mmol), Na2CO3 (3.6 equiv.) was added and solution purged with argon for 15 min. Then Pd(PPh3)4 (0.05 equiv.) was added and argon was purged again for 10 min Reaction mass was heated at 100° C. for 2 h. On completion, reaction mixture was diluted with water and extracted with 10% MeOH/DCM. Combined organic layers were dried over Na2SO4 and solvent removed under reduced pressure to afford crude material which was purified by column chromatography over silica gel to afford the desired compound. (38% yield). LCMS: 491.25 (M+1)+; HPLC: 95.01% (@ 254 nm) (Rt;5.463); 1H NMR (DMSO-d6, 400 MHz) δ 11.55 (s, 1H), 8.87 (s, 1H), 8.26 (s, 1H), 7.79 (s, 1H), 6.80 (s, 1H), 5.91 (s, 1H), 5.22-5.19 (m, 1H), 4.39 (d, 2H, J=4.0 Hz), 2.42-2.40 (m, 4H), 2.24 (s, 3H), 1.49 (d, 6H, J=6 Hz), 1.24 (s, 6H), 1.14 (s, 6H), 1.11 (m, 3H).

Aufarbeitung

  1. customsolution purged with argon for 15 min
  2. customargon was purged again for 10 min
  3. customReaction mass
  4. customOn completion, reaction mixture
  5. extractionextracted with 10% MeOH/DCM
  6. dry with materialCombined organic layers were dried over Na2SO4 and solvent
  7. customremoved under reduced pressure
  8. customto afford crude material which
  9. customwas purified by column chromatography over silica gel

Quellen und Nachweise

ORD-Eintrag
ord-2574bbe2c5f645d9a91a683803ce0d83
Quelldatensatz
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08598167B1

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