Diisopropylethylamine → 2-[1-(2-Tert-butyl-6-chloro-5-methyl-pyrimidin-4-yl)-piperidin-4-yl]-[1,8]naphthyridine

HRID 1169808Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1169808
C(N(C(C)C)CC)(C)C.[C:10]([C:14]1[N:19]=[C:18]([Cl:20])[C:17]([CH3:21])=[C:16](Cl)[N:15]=1)([CH3:13])([CH3:12])[CH3:11].[NH:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:38]=[CH:37][C:36]3[C:31](=[N:32][CH:33]=[CH:34][CH:35]=3)[N:30]=2)[CH2:25][CH2:24]1.N1C2C(=CC=CN=2)C=CC=1.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.CC(N(C)C)=O>[C:10]([C:14]1[N:15]=[C:16]([N:23]2[CH2:24][CH2:25][CH:26]([C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[N:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)[CH2:27][CH2:28]2)[C:17]([CH3:21])=[C:18]([Cl:20])[N:19]=1)([CH3:11])([CH3:12])[CH3:13]

Komponenten

9

Edukt 5

HCID 81531DiisopropylethylamineHCID 1360691,8-NaphthyridineHCID 516892Sodium BicarbonateHCID 8246602-Tert-butyl-4,6-dichloro-5-methylpyrimidineHCID 666409192-(Piperidin-4-YL)-1,8-naphthyridine

Produkt 1

HCID 866189282-[1-(2-Tert-butyl-6-chloro-5-methyl-pyrimidin-4-yl)-piperidin-4-yl]-[1,8]naphthyridineAusbeute 65,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

20 ml of dimethylacetamide and 5 ml (17.8 mmoles) of diisopropylethylamine are added into a single-necked flask containing 1.5 g (6.84 mmoles) of 2-tert-butyl-4,6-dichloro-5-methyl-pyrimidine and 1.46 g (6.84 mmoles) of 2-piperidin-4-yl-[1,8]naphthyridine. This mixture is heated at 100° C. overnight. The next day 0.2 equivalent of naphthyridine is added and the mixture is heated for another 6 hours. The reaction mixture is returned to ambient temperature before concentrating to dryness. The residue obtained is taken up in a mixture of water, ethyl acetate and a saturated solution of sodium bicarbonate. The organic phase is separated and the aqueous phase reextracted with ethyl acetate. The collected organic phases are dried over magnesium sulphate then the solvent is evaporated off under reduced pressure (2 kPa). The residue is chromatographed on silica gel eluting with a gradient of heptane-ethyl acetate (70-30) to heptane-ethyl acetate (50-50). 1.77 g of expected product is obtained.

Aufarbeitung

  1. temperaturethe mixture is heated for another 6 hours
  2. customis returned to ambient temperature
  3. concentrationbefore concentrating to dryness
  4. customThe residue obtained
  5. customThe organic phase is separated
  6. dry with materialThe collected organic phases are dried over magnesium sulphate
  7. customthe solvent is evaporated off under reduced pressure (2 kPa)
  8. customThe residue is chromatographed on silica gel eluting with a gradient of heptane-ethyl acetate (70-30) to heptane-ethyl acetate (50-50)

Quellen und Nachweise

ORD-Eintrag
ord-6bae5d17e4d74606bb865bc86c3064c9
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07825119B2

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