Morpholine → 2-(4-Methoxyphenyl)-5-morpholinopyridin-3-amine

HRID 1431557Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1431557
Br[C:2]1[CH:3]=[C:4]([NH2:16])[C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[NH:85]1[CH2:90][CH2:89][O:88][CH2:87][CH2:86]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:15][O:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[C:4]([NH2:16])=[CH:3][C:2]([N:85]3[CH2:90][CH2:89][O:88][CH2:87][CH2:86]3)=[CH:7][N:6]=2)=[CH:9][CH:10]=1

Komponenten

9

Edukt 5

HCID 8083MorpholineHCID 2733832Lithium HexamethyldisilazideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596313025-Bromo-2-(4-methoxyphenyl)pyridin-3-amineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Produkt 1

HCID 596312932-(4-Methoxyphenyl)-5-morpholinopyridin-3-amine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A mixture of 5-bromo-2-(4-methoxyphenyl)pyridin-3-amine (424.5 mg, 1.52 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl, (X-Phos) (58.8 mg, 0.12 mmol), tris(dibenzylideneacetone)dipalladium (0) (56.1 mg, 0.061 mmol), and morpholine (0.66 mL, 7.58 mmol) in dry THF (3.2 mL) was degassed by nitrogen. To this mixture was added lithium bis(trimethylsilyl)amide, 1.0M in THF (8.4 mL, 8.40 mmol) dropwise, and the resulting reaction was heated to 60° C. After 2.5 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic layers were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-100% DCM in EtOAc) to yield 2-(4-methoxyphenyl)-5-morpholinopyridin-3-amine. 1H NMR (400 MHz, CDCl3) δ ppm 7.84 (1H, d, J=2.5 Hz), 7.57 (2H, m), 6.98 (2H, m), 6.53 (1H, d, J=2.5 Hz), 3.92 (9H, m), 3.22 (4H, m). Mass Spectrum (pos.) m/e: 286.1 (M+1).

Aufarbeitung

  1. customwas degassed by nitrogen
  2. customthe resulting reaction
  3. temperaturethe reaction was cooled to rt
  4. extractionAfter extracting twice with EtOAc and twice with DCM
  5. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified on silica gel (0-100% DCM in EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-bc39388298bb46919c16908e804fcd0f
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940724B2

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