1-Butanol → HCID 178458666, Verbindung

HRID 2189831Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2189831
C1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:18]([F:19])=[CH:17][C:13]([C:14]([NH2:16])=O)=[C:12](N[C@H](C4C=CC(F)=CC=4)C)[N:11]=3)[CH:5]=2)CC1.[NH2:30][C@H:31]([C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)[CH2:32][OH:33].CCN(C(C)C)[CH:44]([CH3:46])[CH3:45].CCCC[OH:54]>>[F:19][C:18]1[C:10]([NH:9][C:6]2[CH:5]=[C:4]([O:54][CH:44]([CH3:46])[CH3:45])[NH:8][N:7]=2)=[N:11][C:12]([NH:30][C@H:31]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[CH2:32][OH:33])=[C:13]([CH:17]=1)[C:14]#[N:16]

Komponenten

5

Edukt 4

HCID 2631-ButanolHCID 81531DiisopropylethylamineHCID 10583003(R)-2-Amino-2-(4-fluorophenyl)ethanolHCID 67455185(S)-6-(5-Cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)nicotinamide

Produkt 1

HCID 178458666HCID 178458666, VerbindungAusbeute 31 %

Reaktionsbedingungen

Temperatur
135 °C

Versuchsvorschrift

2-Chloro-5-fluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)nicotinonitrile (Method 2; 1.6 g, 5.0 mmol) and (R)-2-amino-2-(4-fluorophenyl)ethanol (2.0 g, 11.0 mmol) were added to a solution of n-BuOH (8 ml) and DIEA (0.8 g, 6.0 mmol) in a sealed tube. The reaction was heated to 135° C. for 72 hrs, cooled to 25° C., and concentrated. The resulting residue was purified by column chromatography (DCM-MeOH=50:1) to give the title compound (0.7 g, 31%). 1H NMR (400 MHz, CD3OD) δ 7.49 (d, J=9.5 Hz, 1H), 7.41-7.38 (m, 2H), 7.07-7.02 (m, 2H), 5.40 (s, 1H), 5.10-5.01 (m, 1H), 4.62-4.55 (m, 1H), 3.91-3.79 (m, 2H), 1.33-1.31 (m, 6H). MS: Calcd.: 414. Found: [M+H]+ 415.

Aufarbeitung

  1. temperaturecooled to 25° C.
  2. concentrationconcentrated
  3. customThe resulting residue was purified by column chromatography (DCM-MeOH=50:1)

Quellen und Nachweise

ORD-Eintrag
ord-11af05461baa455084bb8ed9627ff5b4
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08324252B2

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