Reaktion #163048

Reaktionsgleichung

(R)-2-(3-(Aminomethyl)-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoropyridin-2-ylamino)-2-(4-fluorophenyl)ethanol

acetic acid

→

title compound

Ausbeute 48.0%

(R)—N-((6-(5-Cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)-2-hydroxyethylamino)pyridin-3-yl)methyl)acetamide

Ausbeute 48.0%

Lösungsmittel

THF DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe reaction was filtered
2. 2
   Waschenthe resulting resin was washed with a THF-DCM solution (1:1, 3×5 ml for 30 min. each)
3. 3
   Einengenconcentrated
4. 4
   SonstigeThe resulting solid was purified by reverse-phase column chromatography (5-50% CH3CN in H2O over 400 ml)

Vorschrift

(R)-2-(3-(Aminomethyl)-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoropyridin-2-ylamino)-2-(4-fluorophenyl)ethanol (Example 8; 0.034 g, 0.085 mmol) and acetic acid loaded TFP resin (1.4 mmol/g loading, 0.085 mmol) were placed in a THF-DCM solution (1:1, 3 ml) at 0° C. The resulting suspension was shaken vigorously at 0° C. for 45 min. The reaction was filtered and the resulting resin was washed with a THF-DCM solution (1:1, 3×5 ml for 30 min. each). The resulting organic layers were combined and concentrated. The resulting solid was purified by reverse-phase column chromatography (5-50% CH3CN in H2O over 400 ml) to give the title compound (0.018 g, 48%). 1H NMR (400 MHz, CD3OD) δ 7.42-7.36 (m, 2H), 7.12 (d, J=9.6 Hz, 1H), 7.04-6.99 (m, 2H), 6.09 (br s, 1H), 5.19-5.02 (m, 1H), 4.36-4.17 (m, 2H), 3.83-3.71 (m, 2H), 1.99 (s, 3H), 1.88-1.83 (m, 1H), 0.98-0.87 (m, 2H), 0.72-0.66 (m, 2H). MS: Calcd.: 442. Found: [M+H]+ 443.

Quelle