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

HRID 246155

Reaktionsgleichung

Reaktionsgleichung von HRID 246155
[OH:1][CH2:2][C@@H:3]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])[CH3:4].C(O)(C(F)(F)F)=O.C(N)CN>ClCCl>[OH:1][CH2:2][C@@H:3]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])[CH3:4]

Komponenten

5

Edukt 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712861022-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide

Produkt 1

HCID 712879172-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amideAusbeute 36 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In a sealed 25 mL round-bottom flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide (41 mg, 0.080 mmol) and TFA (0.6 ml, 7.8 mmol) were combined with dichloromethane (2 ml) to give an orange solution. The reaction mixture was stirred at room temperature until the consumption of starting material (2.5 h). The reaction mixture was then concentrated under reduced pressure. The resultant crude solid was dissolved in dichloromethane (2 mL) and ethylenediamine (400 μl, 5.9 mmol) was added. The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated and the residue was precipitated with water. The suspension was stirred for 1 h and the crude solid collected by filtration. The crude solid was purified by trituration (9:1 dichloromethane/MeOH) to afford 11 mg (36%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide as an off-white solid. MS: [M+H]+=385; 1H NMR (300 MHz, DMSO-d6) δ: 12.84 (br. s., 1H), 9.13 (s, 1H), 8.66 (d, J=8.7 Hz, 1H), 8.43 (s, 1H), 8.21 (d, J=8.3 Hz, 1H), 7.91-8.04 (m, 1H), 7.32 (dd, J=8.7, 1.5 Hz, 1H), 5.09 (t, J=5.1 Hz, 1H), 4.18 (s, 3H), 4.08-4.33 (m, 1H), 3.58 (t, J=4.7 Hz, 2H), 1.28 (d, J=6.8 Hz, 3H).

Aufarbeitung

  1. customto give an orange solution
  2. concentrationThe reaction mixture was then concentrated under reduced pressure
  3. dissolutionThe resultant crude solid was dissolved in dichloromethane (2 mL)
  4. stirringThe reaction mixture was stirred at room temperature for 18 h
  5. concentrationThe reaction mixture was concentrated
  6. customthe residue was precipitated with water
  7. stirringThe suspension was stirred for 1 h
  8. filtrationthe crude solid collected by filtration
  9. customThe crude solid was purified by trituration (9:1 dichloromethane/MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-8e4817a8b4de47798602365a5234cc4a
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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