5-Bromothiophene-3-carboxamide → HCID 59022988, Verbindung

HRID 1921769Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1921769
C(OC(=O)[N:7]([C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)=[CH:32][CH:31]=1)[C:8]1[C:9]2[N:10]([CH:27]=[CH:28][N:29]=2)[C:11]([Sn](CCCC)(CCCC)CCCC)=[CH:12][N:13]=1)(C)(C)C.Br[C:45]1[S:49][CH:48]=[C:47]([C:50]([NH2:52])=[O:51])[CH:46]=1>CN(C=O)C.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>[NH3:7].[CH3:42][N:39]1[CH2:40][CH2:41][N:36]([C:33]2[CH:34]=[CH:35][C:30]([NH:7][C:8]3[C:9]4[N:10]([CH:27]=[CH:28][N:29]=4)[C:11]([C:45]4[S:49][CH:48]=[C:47]([C:50]([NH2:52])=[O:51])[CH:46]=4)=[CH:12][N:13]=3)=[CH:31][CH:32]=2)[CH2:37][CH2:38]1

Komponenten

6

Edukt 2

HCID 189380635-Bromothiophene-3-carboxamideHCID 67117498HCID 67117498, Verbindung

Produkt 2

HCID 222AmmoniaHCID 59022988HCID 59022988, VerbindungAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a solution of [4-(4-methyl-piperazin-1-yl)-phenyl]-(5-tributylstannanyl-imidazo[1,2-a]pyrazin-8-yl)-carbamic acid tert-butyl ester (0.106 g, 0.15 mmol) in DMF (3 mL) is added 5-bromo-thiophene-3-carboxylic acid amide (0.062 g, 0.3 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.018 g, 0.015 mmol). The solution is degassed and heated at 85° C. for 18 hours. The reaction mixture is diluted with ethyl acetate and washed with water (3×) and brine. The aqueous layers are backwashed with ethyl acetate and the organic layers are combined, dried (MgSO4), and concentrated. The crude mixture is then stirred in (1:1) TFA: dichloromethane (3 mL) for 2 hours at room temperature. The resulting solution is diluted with ethyl acetate and washed with water, sat. NaHCO3 and brine. The aqueous layers are backwashed with ethyl acetate and the organic layers are combined, dried (MgSO4), and concentrated. The crude material is purified by flash column chromatography using 99:1 and 95:5 DCM:NH3 (7M in MeOH), to give 5-{8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-thiophene-3-carboxylic acid amide (0.013 g, 20%) as a yellow solid. LCMS: Rt 2.79 min, (93.3%), m/z (APCI) 434 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.26 (3H, s), 2.48-2.53 (4H, m), 3.14 (4H, m), 6.96 (2H, d), 7.42 (1H, br s), 7.61 (1H, s), 7.78 (1H, s), 7.82 (2H, d), 7.92 (1H, s), 7.99 (1H, br s), 8.21 (1H, s), 8.31 (1H, s), 9.61 (1H, s).

Aufarbeitung

  1. customThe solution is degassed
  2. additionThe reaction mixture is diluted with ethyl acetate
  3. washwashed with water (3×) and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. additionThe resulting solution is diluted with ethyl acetate
  7. washwashed with water, sat. NaHCO3 and brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe crude material is purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-49001583ede645a59eb5f4d1bca218ba
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173656B2

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