Hydrochloric Acid → HCID 178493722, Verbindung

HRID 510903

Reaktionsgleichung

Reaktionsgleichung von HRID 510903
Br[C:2]1[C:3]([O:28][CH3:29])=[C:4]([CH:10]([NH:12][C:13]2[N:21]=[CH:20][N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][N:17]3C2CCCCO2)[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].[CH3:30][O:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[N:36][CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl.O>CO.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.O1CCOCC1>[Cl:9][C:6]1[C:7]([CH3:8])=[C:2]([C:34]2[CH:35]=[N:36][CH:37]=[C:32]([O:31][CH3:30])[CH:33]=2)[C:3]([O:28][CH3:29])=[C:4]([CH:10]([NH:12][C:13]2[N:21]=[CH:20][N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][NH:17]3)[CH3:11])[CH:5]=1

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 10340Sodium CarbonateHCID 27630875-Methoxypyridine-3-boronic AcidHCID 86666818N-[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Produkt 1

HCID 178493722HCID 178493722, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 887MethanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Into a microwave vial was added N-[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (0.12 g, 0.25 mmol) isolated in step 2, (5-methoxypyridin-3-yl)boronic acid (0.046 g, 0.30 mmol), 10% sodium carbonate (0.60 mL, 0.62 mmol), 1,4-dioxane (1.5 mL) and tetrakis(triphenylphosphine)palladium(0) (0.017 g, 0.015 mmol), the mixture was bubbled with N2 for 5 min and then heated at 100° C. for 2 hours. The resulting mixture was cooled to room temperature and then treated directly with 6.0 M hydrogen chloride in water (0.4 mL, 2 mmol) for ˜30 minutes. The mixture was diluted with MeOH, filtered and purified on Prep LCMS (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired single enantiomer product. LCMS calculated for C21H22ClN6O2 (M+H)+: m/z=425.1. found: 425.1. 1H NMR (DMSO-d6, 300 MHz) δ 8.27-7.99 (6H, m), 7.63 (1H, s), 5.71 (1H, m), 3.79 (3H, s), 3.40 (3H, s), 1.94 (3H, s), 1.44 (3H, d, J=6.9 Hz) ppm.

Aufarbeitung

  1. customthe mixture was bubbled with N2 for 5 min
  2. temperatureThe resulting mixture was cooled to room temperature
  3. filtrationfiltered
  4. custompurified on Prep LCMS (XBridge C18 Column
  5. washeluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at flow rate of 60 mL/min)
  6. customto give the desired single enantiomer product

Quellen und Nachweise

ORD-Eintrag
ord-76b10d7c7d5e4eda975e6fda8daa0b8f
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096600B2

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