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Pyridine → HCID 23516247, Verbindung

HRID 2181430
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2181430
[Cl:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:18]([F:19])=[C:17]([F:20])[CH:16]=[CH:15][C:11]=1[C:12]([OH:14])=[O:13].N1C=CC=CC=1.FC(F)(F)C(O[C:32]1[C:37]([F:38])=[C:36]([F:39])[C:35]([F:40])=[C:34]([F:41])[C:33]=1[F:42])=O>CN(C)C=O.C(OCC)(=O)C>[F:38][C:37]1[C:32]([O:13][C:12](=[O:14])[C:11]2[CH:15]=[CH:16][C:17]([F:20])=[C:18]([F:19])[C:10]=2[NH:9][C:3]2[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=2[Cl:1])=[C:33]([F:42])[C:34]([F:41])=[C:35]([F:40])[C:36]=1[F:39]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 1049PyridineHCID 4327891Pentafluorophenyl TrifluoroacetateHCID 10112191Zapnometinib

Produkt 1

HCID 23516247HCID 23516247, VerbindungAusbeute 91,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel
HCID 8857
Ethyl Acetate
Lösungsmittel

Versuchsvorschrift

To a solution of the product of Example 2, Step A, 2-(2-chloro-4-iodophenylamino)-3,4-difluorobenzoic acid (10.0 g, 24.4 mmol), and pyridine (2.16 mL, 26.8 mmol) in anhydrous dimethylformamide (49 mL) was added pentafluorophenyl trifluoroacetate (5.35 mL, 30.5 mmol). The resultant solution was stirred at ambient temperature for 2 hours. The reaction mixture was diluted with ethyl acetate (600 mL) and washed with 0.1 M aqueous hydrochloric acid (2×240 mL), 25% saturated aqueous sodium bicarbonate (2×240 mL), and saturated brine (240 mL). The organics were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to afford an oil that was purified on silica gel. Elution with hexanes-ethyl acetate (19:1) afforded 2-(2-chloro-4-iodophenylamino)-3,4-difluorobenzoic acid pentafluorophenyl ester (12.8 g, 91%) as a pale-yellow powder: m.p. 108.5-110.0° C.; 1H-NMR (400 MHz, CDCl3) δ 8.77 (br s, 1H), 8.07 (br s, 1 H), 7.69 (br s, 1H), 7.48 (br d, J=7.0 Hz, 1H), 6.91 (br d, J=7.2 Hz, 1 H), 6.67 (br s, 1H); 19F-NMR (376 MHz, CDCl3) δ −123.74 (s, 1F), −139.17 (d, J=16.8 Hz, 1F), −152.35 (d, J=21.4 Hz, 2F), −156.96 (t, J=21.4 Hz, 1F), −161.81 (t, J=21.4 Hz, 2F). Anal. Calcd/found for C19H6NO2F7ClI: C, 39.65/39.32; H, 1.05/0.91; N, 2.43/2.35; F, 23.10/22.85; Cl, 6.16/6.92; I, 22.05/22.50. Step C: Preparation of 2-(2-chloro-4-iodo-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide

Aufarbeitung

  1. washwashed with 0.1 M aqueous hydrochloric acid (2×240 mL), 25% saturated aqueous sodium bicarbonate (2×240 mL), and saturated brine (240 mL)
  2. dry with materialThe organics were dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto afford an oil that
  5. customwas purified on silica gel
  6. washElution with hexanes-ethyl acetate (19:1)

Quellen und Nachweise

ORD-Eintrag
ord-8720b89759ac42c08ba504326e561cf0
Quelldatensatz
uspto-grants-2005_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US06891066B2

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