Triethylamine → 2-Chloro-N-(4,4-difluorocyclohexyl)-5,6-dimethylpyrimidin-4-amine

HRID 63118

Reaktionsgleichung

[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH3:9])=[C:4]([CH3:10])[N:3]=1.Cl.[F:12][C:13]1([F:20])[CH2:18][CH2:17][CH:16]([NH2:19])[CH2:15][CH2:14]1.C(N(CC)CC)C>CN(C)C=O>[Cl:1][C:2]1[N:7]=[C:6]([NH:19][CH:16]2[CH2:17][CH2:18][C:13]([F:20])([F:12])[CH2:14][CH2:15]2)[C:5]([CH3:9])=[C:4]([CH3:10])[N:3]=1

Komponenten

Reaktionsbedingungen

Temperatur: 50 °C

Versuchsvorschrift

To the solution of 2,4-dichloro-5,6-dimethylpyrimidine (0.585 g, 3.304 mmol, Example 1, Step C) in N,N-dimethylformamide (10 mL), (4,4-difluorocyclohexyl)amine hydrochloride (0.652 g, 3.800 mmol) and triethylamine (1.338 g, 13.218 mmol) were added, and reaction mixture was heated at 50° C. overnight. Volatiles were removed under reduced pressure, and the residue was poured into water (300 mL). The mixture was extracted with ether (3×50 mL), dried over sodium sulfate, filtered, and concentrated. The residue was subjected to column chromatography on silica eluting with a mixture of hexane/ethyl acetate (gradient 4:1-2:1) to provide 621 mg (68%) of the titled compound as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.18-1.24 (m, 1H), 1.60-1.72 (m, 2H), 1.80-2.10 (m, 8H) 2.21 (s, 3H), 4.00-4.10 (m, 1H), 6.73 (d, J=7.79 Hz, 1H); MS (ESI) m/z 318.6 (M+1)+.

Aufarbeitung

customreaction mixture
customVolatiles were removed under reduced pressure
additionthe residue was poured into water (300 mL)
extractionThe mixture was extracted with ether (3×50 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
additionThe residue was subjected to column chromatography on silica eluting with a mixture of hexane/ethyl acetate (gradient 4:1-2:1)

Quellen und Nachweise

ORD-Eintrag: ord-b129f796158b41c2b10fb2ee0dcb23b6
Quelldatensatz: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09447051B2

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