Potassium Carbonate → 5-(2-Amino-5-bromo-pyridin-3-yl)-3-[1-(2-chloro-phenyl)-ethoxy]-thiophene-2-carboxylic acid methyl ester

HRID 533229Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 533229
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7](B2OC(C)(C)C(C)(C)O2)=[CH:8][C:9]=1[O:10][CH:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19])[CH3:12])=[O:4].[Br:29][C:30]1[CH:31]=[C:32](I)[C:33]([NH2:36])=[N:34][CH:35]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:32]2[C:33]([NH2:36])=[N:34][CH:35]=[C:30]([Br:29])[CH:31]=2)=[CH:8][C:9]=1[O:10][CH:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19])[CH3:12])=[O:4]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 15165082-Amino-5-bromo-3-iodopyridineHCID 58970492HCID 58970492, Verbindung

Produkt 1

HCID 596673595-(2-Amino-5-bromo-pyridin-3-yl)-3-[1-(2-chloro-phenyl)-ethoxy]-thiophene-2-carboxylic acid methyl esterAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittel

Versuchsvorschrift

3-[1-(2-Chloro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiophene-2-carboxylic acid methyl ester (150 mg, 0.37 mmol, 1.1 Eq.), 5-Bromo-3-iodo-pyridin-2-ylamine (100 mg, 0.34 mmol, 1.0 Eq.) and Pd(PPh3)4 (39 mg, 0.04 mmol, 0.1 Eq.) were dissolved in toluene (1.6 mL) and EtOH (0.4 mL). 2M K2CO3 (0.5 mL, 1.0 mmol, 3.0 Eq) and the reaction heated under microwave conditions at 140° C. for 15 minutes. The reaction was partitioned between EtOAc (10 mL) and water (10 mL) and the aqueous phase extracted with EtOAc (3×10 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (40% EtOAc/petroleum Ether) to give the sub-title compound as an off-white solid (125 mg, 0.27 mmol, 80%); 1H NMR (400 MHz, CDCl3) δ 1.74 (3H, d), 3.92 (3H, s), 4.71 (2H, br s), 5.81 (1H, q), 6.81 (1H, s), 7.24-7.32 (2H, m), 7.38 (1H, dd), 7.54 (1H, d), 7.66 (1H, dd), 8.10 (1H, d)

Aufarbeitung

  1. customThe reaction was partitioned between EtOAc (10 mL) and water (10 mL)
  2. extractionthe aqueous phase extracted with EtOAc (3×10 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography (40% EtOAc/petroleum Ether)

Quellen und Nachweise

ORD-Eintrag
ord-293bf07016e7404692a59422e6d6118d
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08853244B2

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