Water → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-(3-cyano-pyrrolidin-1-yl)-1-methyl-ethyl]-amide

HRID 246106Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246106
[C:1]([CH:3]1[CH2:7][CH2:6][N:5]([CH2:8][CH:9]([NH:11][C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[C:31]5[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=5)[N:25]([CH3:33])[N:24]=4)[N:21]=3)[N:16](COCC[Si](C)(C)C)[CH:15]=2)=[O:13])[CH3:10])[CH2:4]1)#[N:2].FC(F)(F)C(O)=O.C(N)CN.O>ClCCl.C(OCC)(=O)C>[C:1]([CH:3]1[CH2:7][CH2:6][N:5]([CH2:8][CH:9]([NH:11][C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[C:31]5[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=5)[N:25]([CH3:33])[N:24]=4)[N:21]=3)[NH:16][CH:15]=2)=[O:13])[CH3:10])[CH2:4]1)#[N:2]

Komponenten

7

Edukt 4

HCID 962WaterHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712861852-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-(3-cyano-pyrrolidin-1-yl)-1-methyl-ethyl]-amide

Produkt 1

HCID 712860302-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-(3-cyano-pyrrolidin-1-yl)-1-methyl-ethyl]-amideAusbeute 52,3 %

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 [2-(3-cyano-pyrrolidin-1-yl)-1-methyl-ethyl]-amide (37 mg, 0.062 mmol) was dissolved in dichloromethane (0.8 ml) and cooled in ice bath. Trifluoroacetic acid (0.4 ml) was slowly added and the reaction was stirred at room temperature for 2 h. The reaction was evaporated and the residue was dissolved in dichloromethane (1.2 ml). Ethylenediamine (0.25 ml, 3.7 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 more with ethyl acetate. The combined organic layers were washed with sodium chloride solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) to afford 15 mg (52%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-(3-cyano-pyrrolidin-1-yl)-1-methyl-ethyl]-amide. MS: (M+H)+=463; mp=206-209° C. 1H NMR (300 MHz, DMSO-d6) δ: 12.83-12.94 (m, 1H), 9.10 (s, 1H), 8.38-8.51 (m, 2H), 8.04-8.13 (m, 1H), 7.99-8.04 (m, 1H), 7.30-7.39 (m, 1H), 4.20-4.36 (m, 1H), 4.18 (s, 3H), 3.07-3.22 (m, 1H), 2.53-2.88 (m, 5H), 1.99-2.15 (m, 1H), 1.74-1.92 (m, 1H), 1.33 (d, J=6.4 Hz, 3H).

Aufarbeitung

  1. temperaturecooled in ice bath
  2. customThe reaction was evaporated
  3. dissolutionthe residue was dissolved in dichloromethane (1.2 ml)
  4. stirringthe mixture was stirred for 18 h
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted twice more with ethyl acetate
  7. washThe combined organic layers were washed with sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. customAfter evaporation
  10. customthe residue was purified by silica gel chromatography (methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-2da3519908db48a1968a0e1a2d25866f
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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