Acetic Acid → HCID 178474560, Verbindung

HRID 75876

Reaktionsgleichung

[NH2:1][CH2:2][C:3]1[C:4]([NH:20][C@H:21]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH3:22])=[N:5][C:6]([NH:10][C:11]2[CH:15]=[C:14]([O:16][CH:17]([CH3:19])[CH3:18])[NH:13][N:12]=2)=[C:7]([F:9])[CH:8]=1.[C:30](O)(=[O:32])[CH3:31]>C1COCC1.C(Cl)Cl>[F:9][C:7]1[CH:8]=[C:3]([CH2:2][NH:1][C:30](=[O:32])[CH3:31])[C:4]([NH:20][C@H:21]([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[CH3:22])=[N:5][C:6]=1[NH:10][C:11]1[CH:15]=[C:14]([O:16][CH:17]([CH3:18])[CH3:19])[NH:13][N:12]=1

Komponenten

Reaktionsbedingungen

Temperatur: 0 °C

Versuchsvorschrift

(S)-3-(Aminomethyl)-5-fluoro-N2-(1-(4-fluorophenyl)ethyl)-N6-(5-isopropoxy-1H-pyrazol-3-yl)pyridine-2,6-diamine (Example 18; 0.20 g, 0.49 mmol) and acetic acid loaded TFP resin (1.4 mmol/g loading, 0.49 mmol) were placed in a THF-DCM solution (1:1, 6 ml) at 0° C. The resulting solution was shaken vigorously at 0° C. for 45 min and filtered. 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 (0.010 g, 49%). 1H NMR (400 MHz, CD3OD) δ 7.37-7.34 (m, 2H), 7.14 (d, J=10.9 Hz, 1H), 7.02-6.98 (m, 2H), 5.25 (s, 1H), 4.96-4.95 (m, 1H), 4.55-4.52 (m, 1H), 4.30 (d, J=14.8 Hz, 1H), 4.21 (d, J=14.8 Hz, 1H), 2.01 (s, 3H), 1.51 (d, J=6.8 Hz, 3H), 1.31 (d, J=6.0 Hz, 6H). MS: Calcd.: 444. Found: [M+H]+ 445.

Aufarbeitung

filtrationfiltered
washThe resulting resin was washed with a THF-DCM solution (1:1, 3×5 ml for 30 min. each)
concentrationconcentrated
customThe resulting solid was purified by reverse-phase column chromatography (5-50% CH3CN in H2O over 400 ml)

Quellen und Nachweise

ORD-Eintrag: ord-9ea7d69e3c7e44c4ae2960e2c674b0f9
Quelldatensatz: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08835465B2

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