Water → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (S)-N-(tetrahydro-pyran-3-yl)-amide

HRID 246134Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246134
[O:1]1[CH2:6][CH2:5][CH2:4][C@H:3]([NH:7][C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[C:27]5[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=5)[N:21]([CH3:29])[N:20]=4)[N:17]=3)[N:12](COCC[Si](C)(C)C)[CH:11]=2)=[O:9])[CH2:2]1.FC(F)(F)C(O)=O.C(N)CN.O>ClCCl.C(OCC)(=O)C>[O:1]1[CH2:6][CH2:5][CH2:4][C@H:3]([NH:7][C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[C:27]5[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=5)[N:21]([CH3:29])[N:20]=4)[N:17]=3)[NH:12][CH:11]=2)=[O:9])[CH2:2]1

Komponenten

7

Edukt 4

HCID 962WaterHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712860382-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (S)-N-(tetrahydro-pyran-3-yl)-amide

Produkt 1

HCID 712884072-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (S)-N-(tetrahydro-pyran-3-yl)-amideAusbeute 73 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (S)—N-(tetrahydro-pyran-3-yl)-amide (55 mg, 0.10 mmol) was dissolved in dichloromethane (1.2 ml) and cooled in ice bath. Trifluoroacetic acid (0.6 ml) was slowly added and the reaction was stirred at room temperature for 3 h. The reaction was evaporated and the residue was dissolved in dichloromethane (1 ml). Ethylenediamine (0.41 ml, 6.1 mmol) was added and the mixture was stirred for 18 h. Water and then ethyl acetate were added to the mixture. The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with sodium chloride solution, dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography (methanol/dichloromethane) to give 30 mg (71%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (S)—N-(tetrahydro-pyran-3-yl)-amide. MS: (M+H)+=411; mp=320-323° C. 1H NMR (300 MHz, DMSO-d6) δ: 9.10 (s, 1H), 8.50 (d, J=8.7 Hz, 1H), 8.44 (s, 1H), 8.16 (d, J=7.6 Hz, 1H), 7.96 (d, J=1.9 Hz, 1H), 7.24 (dd, J=8.5, 1.7 Hz, 1H), 4.16 (s, 3H), 4.04-4.14 (m, 1H), 3.86-3.94 (m, 1H), 3.62-3.73 (m, 2H), 3.46-3.55 (m, 1H), 1.93-2.08 (m, 1H), 1.69-1.89 (m, 2H), 1.50-1.68 (m, 1H).

Aufarbeitung

  1. temperaturecooled in ice bath
  2. customThe reaction was evaporated
  3. dissolutionthe residue was dissolved in dichloromethane (1 ml)
  4. stirringthe mixture was stirred for 18 h
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted twice with ethyl acetate
  7. washThe combined organic layers were washed with sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. customevaporated
  10. customThe residue was purified by silica gel chromatography (methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-d8b65bac5dda4559bb6d7f4d5f6c47e7
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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