Diisopropylethylamine → (S)-N2-(5-Cyclopropyl-1H-pyrazol-3-yl)-3-fluoro-N6-(1-(4-fluorophenyl)ethyl)-5-nitropyridine-2,6-diamine

HRID 75887

Reaktionsgleichung

Reaktionsgleichung von HRID 75887
[F:1][C:2]1[CH:3]=[C:4]([N+:19]([O-:21])=[O:20])[C:5]([NH:9][C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH3:11])=[N:6][C:7]=1F.[CH:22]1([C:25]2[NH:29][N:28]=[C:27]([NH2:30])[CH:26]=2)[CH2:24][CH2:23]1.CCN(C(C)C)C(C)C>C1COCC1>[CH:22]1([C:25]2[NH:29][N:28]=[C:27]([NH:30][C:7]3[C:2]([F:1])=[CH:3][C:4]([N+:19]([O-:21])=[O:20])=[C:5]([NH:9][C@H:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)[CH3:11])[N:6]=3)[CH:26]=2)[CH2:24][CH2:23]1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 27580143-cyclopropyl-1H-pyrazol-5-amineHCID 67452698(S)-5,6-difluoro-N-(1-(4-fluorophenyl)ethyl)-3-nitropyridin-2-amine

Produkt 1

HCID 67454027(S)-N2-(5-Cyclopropyl-1H-pyrazol-3-yl)-3-fluoro-N6-(1-(4-fluorophenyl)ethyl)-5-nitropyridine-2,6-diamineAusbeute 66,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

To a solution of (S)-5,6-difluoro-N-(1-(4-fluorophenyl)ethyl)-3-nitropyridin-2-amine (Method 23, 0.60 g, 2.0 mmol) in THF (10 ml) at room temperature was added 5-cyclopropyl-1H-pyrazol-3-amine (0.50 g, 4.0 mmol), and DIEA (0.26 g, 2.0 mmol). The reaction was then heated to 55° C. for 24 hours, cooled to room temperature, and quenched with water. The reaction was then extracted with DCM (2×75 ml), and the combined organic fractions were dried over Na2SO4, filtered, and then concentrated. The resulting oil was purified by column chromatography (DCM-MeOH=100:1) to give the title compound (0.53 g, 66%). 1H NMR (400 MHz, CD3OD) δ 8.00 (d, J=11.1 Hz, 1H), 7.38-7.35 (m, 2H), 7.07-7.02 (m, 2H), 6.17 (s, 1H), 5.41-5.39 (m, 1H), 1.93-1.87 (m, 1H), 1.61 (d, J=7.0 Hz, 3), 1.02-1.00 (m, 2H), 0.69-0.66 (m, 2H). MS: Calcd.: 400. Found: [M+H]+ 401.

Aufarbeitung

  1. temperaturecooled to room temperature
  2. customquenched with water
  3. extractionThe reaction was then extracted with DCM (2×75 ml)
  4. dry with materialthe combined organic fractions were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting oil was purified by column chromatography (DCM-MeOH=100:1)

Quellen und Nachweise

ORD-Eintrag
ord-9c2a28e7f4ea41ffaf0f6496383203e8
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835465B2

Verknüpfte Notizen

Wird geladen…