Tetrabutylammonium Fluoride → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4,5-dihydro-oxazol-2-yl)-ethyl]-amide

HRID 245931Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245931
[O:1]1[CH2:5][CH2:4][N:3]=[C:2]1[C@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH3:30])[N:21]=3)[N:18]=2)[N:13](COCC[Si](C)(C)C)[CH:12]=1)=[O:10])[CH3:7].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>>[O:1]1[CH2:5][CH2:4][N:3]=[C:2]1[C@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH3:30])[N:21]=3)[N:18]=2)[NH:13][CH:12]=1)=[O:10])[CH3:7]

Komponenten

3

Edukt 2

HCID 2724141Tetrabutylammonium FluorideHCID 71288191HCID 71288191, Verbindung

Produkt 1

HCID 712882002-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4,5-dihydro-oxazol-2-yl)-ethyl]-amideAusbeute 41,4 %

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

In a small vial, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4,5-dihydro-oxazol-2-yl)-ethyl]-amide (85 mg, 0.16 mmol) was dissolved in tetrabutylammonium fluoride (1.0 M in THF, 1.6 ml, 1.6 mmol). The yellow reaction mixture was stirred at 60° C. overnight then cooled to room temperature, quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-5% MeOH) to afford 27 mg (40%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4,5-dihydro-oxazol-2-yl)-ethyl]-amide as an off-white solid. MS: (M+Na)+=430; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.93 (br. s., 1H), 9.14 (s, 1H), 8.69 (dd, J=9.1, 5.3 Hz, 1H), 8.57 (d, J=8.3 Hz, 1H), 8.49 (s, 1H), 7.69 (dd, J=9.8, 1.9 Hz, 1H), 7.14 (td, J=9.1, 2.3 Hz, 1H), 4.97 (quin, J=7.5 Hz, 1H), 4.27-4.39 (m, 2H), 4.16 (s, 3H), 3.79 (td, J=9.3, 4.3 Hz, 2H), 1.50 (d, J=7.2 Hz, 3H).

Aufarbeitung

  1. temperaturethen cooled to room temperature
  2. customquenched with water
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialthen dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-5% MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-00837e1f424e4e399121f62a0082d76c
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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