Methanol → Tert-butyl 4-((3-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-5-(6-formylpyridin-3-yl)-2-methylphenyl)(methyl)amino)piperidine-1-carboxylate

HRID 1616386Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1616386
Br[C:2]1[CH:3]=[C:4]([C:24](=[O:36])[NH:25][CH2:26][C:27]2[C:28](=[O:35])[NH:29][C:30]([CH3:34])=[CH:31][C:32]=2[CH3:33])[C:5]([CH3:23])=[C:6]([N:8]([CH3:22])[CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH:7]=1.[CH:37]([C:39]1[N:44]=[CH:43][C:42](B(O)O)=[CH:41][CH:40]=1)=[O:38].C([O-])([O-])=O.[Na+].[Na+].CO>O1CCOCC1.C(Cl)Cl.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>[CH3:33][C:32]1[CH:31]=[C:30]([CH3:34])[NH:29][C:28](=[O:35])[C:27]=1[CH2:26][NH:25][C:24]([C:4]1[C:5]([CH3:23])=[C:6]([N:8]([CH3:22])[CH:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:13][CH2:14]2)[CH:7]=[C:2]([C:42]2[CH:43]=[N:44][C:39]([CH:37]=[O:38])=[CH:40][CH:41]=2)[CH:3]=1)=[O:36]

Komponenten

8

Edukt 4

HCID 887MethanolHCID 10340Sodium CarbonateHCID 45073592(6-Formylpyridin-3-YL)boronic acidHCID 70872376Tert-butyl 4-((5-bromo-3-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl) methyl)carbamoyl)-2-methylphenyl)(methyl)amino)piperidin-1-carboxylate

Produkt 1

HCID 86684892Tert-butyl 4-((3-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-5-(6-formylpyridin-3-yl)-2-methylphenyl)(methyl)amino)piperidine-1-carboxylateAusbeute 87,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Tert-butyl 4-((5-bromo-3-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-2-methylphenyl)(methyl)amino)piperidin-1-carboxylate (0.5 g, 0.892 mmol), (6-formylpyridin-3-yl)boronic acid (0.31 g, 1.33 mmol) and Pd(PPh3)4 (0.103 g, 0.082 mmol) in 1,4-dioxane (10 mL) was purged with argon for 10 min. Then, 2 M Na2CO3 solution (0.34 g, 3.21 mmol) was added to it and again argon was purged through it for 10 min. The reaction mixture was stirred at 100° C. for 2 h. After completion of the reaction, water was added to it and extraction was carried out using 5% MeOH in DCM. 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 over silica gel (60-120 mesh size) to afford tert-butyl 4-((3-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-5-(6-formylpyridin-3-yl)-2-methylphenyl)(methyl)amino)piperidine-1-carboxylate (0.40 g, 87.9%).

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 over silica gel (60-120 mesh size)

Quellen und Nachweise

ORD-Eintrag
ord-a0fe441b63a742b3b09582f44e8fd7de
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765732B2

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