Hydrazine → 2-[4-(4-Amino-phenylethynyl)-1H-pyrazol-3-yl]-4-chloro-phenol

HRID 2075768

Reaktionsgleichung

Reaktionsgleichung von HRID 2075768
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]=[C:6](I)[C:5]2=O.[C:14]([C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1)#[CH:15].C(N(C(C)C)CC)(C)C.[NH2:32][NH2:33]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CC#N>[NH2:20][C:19]1[CH:21]=[CH:22][C:16]([C:14]#[C:15][C:6]2[C:5]([C:4]3[CH:3]=[C:2]([Cl:1])[CH:11]=[CH:10][C:9]=3[OH:8])=[N:32][NH:33][CH:7]=2)=[CH:17][CH:18]=1

Komponenten

8

Edukt 4

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 37600254-EthynylanilineHCID 116666776-Chloro-3-iodochromone2×

Produkt 1

HCID 1785075482-[4-(4-Amino-phenylethynyl)-1H-pyrazol-3-yl]-4-chloro-phenolAusbeute 48,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a mixture of 6-chloro-3-iodo-chromone (1A, 6.12 g, 20 mmol) and 4-ethynylaniline (2.32 g, 24 mmol) and PdCl2(PPh3)2 (0.28 g, 0.4 mmol) and CuI (38 mg, 0.2 mmol) was added anhydrous CH3CN (200 mL). Upon stirring, diisopropylethylamine (DIPEA, 14 mL, 80 mmol) was added slowly to the above mixture. The reaction mixture was stirred at rt for 7 h. LCMS indicated all of 1A was consumed. Anhydrous hydrazine (5.3 mL, 80 mmol) was then added. The mixture was stirred at rt overnight. Solvent was removed. The residua was dissolved in dichloromethane and loaded onto a silica column eluting with dichloromethane/ethyl acetate (v/v 6/1, 2/1, 1/1, 1/2, 1/5) to afford the title compound 24A (3.02 g) as a yellowish solid in 48.7% yield. 1H NMR (CDCl3, 500 MHz) δ 10.05 (br s, 1H), 8.75 (d, 1H, J=2.0 Hz), 7.84 (s, 1H), 7.42 (d, 2H, J=8.5 Hz), 7.20 (dd, 1H, J=9.0, 2.0 Hz), 6.98 (d, 1H, J=8.5 Hz), 6.68 (d, 2H, J=8.0 Hz), 3.86 (s, 2H). LCMS (ESI) m/z 310.07 (MH+, 100); HPLC: tR=3.78 min.

Aufarbeitung

  1. stirringThe reaction mixture was stirred at rt for 7 h
  2. customwas consumed
  3. stirringThe mixture was stirred at rt overnight
  4. customSolvent was removed
  5. dissolutionThe residua was dissolved in dichloromethane
  6. washeluting with dichloromethane/ethyl acetate (v/v 6/1, 2/1, 1/1, 1/2, 1/5)

Quellen und Nachweise

ORD-Eintrag
ord-50644a70c6b9424a914ffc83f100fa34
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07923004B2

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