Sodium Carbonate → N-((1,2-dihydro-6-methyl-2-oxo-4-propylpyridin-3-yl)methyl)-1-isopropyl-6-(thiophen-3-yl)-1H-indazole-4-carboxamide

HRID 85442Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 85442
Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:28])[NH:20][C:21]([CH3:27])=[CH:22][C:23]=2[CH2:24][CH2:25][CH3:26])=[O:15])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.CC1(C)C(C)(C)OB([C:37]2[CH:41]=[CH:40][S:39][CH:38]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.O.C([O-])(O)=O.[Na+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:27][C:21]1[NH:20][C:19](=[O:28])[C:18]([CH2:17][NH:16][C:14]([C:4]2[C:5]3[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=3[CH:10]=[C:2]([C:37]3[CH:41]=[CH:40][S:39][CH:38]=3)[CH:3]=2)=[O:15])=[C:23]([CH2:24][CH2:25][CH3:26])[CH:22]=1

Komponenten

8

Edukt 3

HCID 10340Sodium CarbonateHCID 27605974,4,5,5-Tetramethyl-2-(thiophen-3-yl)-1,3,2-dioxaborolaneHCID 674653266-bromo-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide

Produkt 1

HCID 54596916N-((1,2-dihydro-6-methyl-2-oxo-4-propylpyridin-3-yl)methyl)-1-isopropyl-6-(thiophen-3-yl)-1H-indazole-4-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

To a stirred solution of 6-bromo-N-((1,2-dihydro-6-methyl-2-oxo-4-propylpyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide (0.2 g, 0.44 mmol) in DMF (10 mL) was added 4,4,5,5-tetramethyl-2-(thiophen-3-yl)-1,3,2-dioxaborolane (0.113 g, 0.53 mmol) followed by PdCl2(PPh3)2 (0.06 g, 0.08 mmol) and the reaction mixture was stirred for 5 min. Sodium carbonate (0.119 g, 0.940 mmol) dissolved in water (2 mL) was added and the contents were stirred at 120° C. for 3 h. The reaction mixture was diluted with NaHCO3 solution and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine solution (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford the crude product. The crude product was purified by silica gel chromatography (eluent: 4% MeOH\EtOAc) to afford the title compound as an off white solid (75 mg, 38%). 1H NMR (DMSO-d6, 400 MHz): δ 0.883 (t, J=7.2 Hz, 3H), 1.491-1.550 (m, 8H), 2.13 (s, 3H), 2.501 (s, 2H), 4.419 (d, J=3.6 Hz, 2H), 5.130 (t, J=6.4 Hz, 1H), 5.912 (s, 1H), 7.691 (s, 1H), 7.766 (d, J=4.4 Hz, 1H), 7.930 (s, 1H), 8.041 (s, 1H), 8.171 (s, 1H), 8.353 (s, 1H), 8.563 (s, 1H), 11.530 (s, 1H). LCMS (ES+) m/z: 449.09.

Aufarbeitung

  1. additionwas added
  2. stirringthe contents were stirred at 120° C. for 3 h
  3. extractionextracted with ethyl acetate (3×20 mL)
  4. washThe combined organic layers were washed with brine solution (20 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford the crude product
  9. customThe crude product was purified by silica gel chromatography (eluent: 4% MeOH\EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-463e358661f44be39e718fccf419be62
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846935B2

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