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2-{6-[(E)-2-(4-fluoro-phenyl)-vinyl]-pyrazin-2-yl}-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide → 2-{6-[2-(4-Fluoro-phenyl)-ethyl]-pyrazin-2-yl}-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide

HRID 1879167
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1879167
[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:14][C:13]([C:15]3[CH:20]=[N:19][CH:18]=[C:17](/[CH:21]=[CH:22]/[C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[N:16]=3)=[N:12][C:11]=2[CH3:30])=[O:9])=[CH:4][CH:3]=1>C(OCC)(=O)C.C(O)C.[Pd]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:14][C:13]([C:15]3[CH:20]=[N:19][CH:18]=[C:17]([CH2:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[N:16]=3)=[N:12][C:11]=2[CH3:30])=[O:9])=[CH:31][CH:32]=1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

4

Edukt 1

HCID 684900412-{6-[(E)-2-(4-fluoro-phenyl)-vinyl]-pyrazin-2-yl}-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide

Produkt 1

HCID 249550612-{6-[2-(4-Fluoro-phenyl)-ethyl]-pyrazin-2-yl}-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamideAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 21584252Ethanol ethylacetateLösungsmittel

Versuchsvorschrift

Part B. To a solution of 2-{6-[(E)-2-(4-fluoro-phenyl)-vinyl]-pyrazin-2-yl}-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide (150 mg, 0.33 mmol, 1.0 equiv) in ethyl acetate/ethanol (1:1) was added Pd/C (70 mg, 10%). The flask was first purged with nitrogen, then with hydrogen in a Parr apparatus. The reaction mixture was stirred at ambient temperature for 12 hr at 50 psi. Upon completion by LCMS, the reaction mixture was diluted with ethyl acetate, filtered through Celite and concentrated in vacuo. The crude product was purified by preparative HPLC (acetonitrile/water, 0.1% trifluoroacetic acid) to afford 2-{6-[2-(4-fluoro-phenyl)-ethyl]-pyrazin-2-yl}-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide (113 mg, 75%). 1H NMR (400 MHz, CD2Cl2) δ 9.15 (s, 1H), 8.36 (s, 1H), 7.33-7.37 (m, 2H), 7.13-7.16 (m, 2H), 7.03-7.08 (m, 2H), 6.92-6.96 (m, 2H), 6.20 (bs, 1H), 4.56 (d, J=4.0 Hz, 2H), 3.08-3.14 (m, 4H), 2.72 (s, 3H); HRMS (M+H)+=451.15.

Aufarbeitung

  1. customThe flask was first purged with nitrogen
  2. additionUpon completion by LCMS, the reaction mixture was diluted with ethyl acetate
  3. filtrationfiltered through Celite
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by preparative HPLC (acetonitrile/water, 0.1% trifluoroacetic acid)

Quellen und Nachweise

ORD-Eintrag
ord-e0587eb4fa0f4d7ca8d5e50ccc32798f
Quelldatensatz
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08314138B2

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