Trifluoroacetic acid → N-((1R,2S)-2-aminocyclohexyl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246401

Reaktionsgleichung

Reaktionsgleichung von HRID 246401
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[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][CH:25]=[C:26]([O:29][CH3:30])[CH:27]=4)[N:22]([CH3:31])[N:21]=3)[N:18]=2)[N:13](COCC[Si](C)(C)C)[CH:12]=1)=[O:10].C(O)(C(F)(F)F)=O>ClCCl>[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[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][CH:25]=[C:26]([O:29][CH3:30])[CH:27]=4)[N:22]([CH3:31])[N:21]=3)[N:18]=2)[NH:13][CH:12]=1)=[O:10]

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acidHCID 71280458N-((1R,2S)-2-aminocyclohexyl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Produkt 1

HCID 71280500N-((1R,2S)-2-aminocyclohexyl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideAusbeute 56,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

To a pale yellow solution of N-((1R,2S)-2-aminocyclohexyl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (21 mg, 38.2 μmol) in dichloromethane (3.00 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmol, Eq: 340), the reaction mixture turned dark red and was stirred at 25° C. overnight then concentrated. The residue was re-dissolved in 5 mL of a solution of (dichloromethane/MeOH/ammonium hydroxide; 60:10:1) and stirred at 25° C. for 3 h, then evaporated to a light yellow solid, dissolved in dichloromethane (added few drops MeOH and heating) and purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 10% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane. The pure product dissolved in hot MeOH and allowed to stand overnight for solid formation. The solid was separated by decantation and dried under high vacuum to give N-((1R,2S)-2-aminocyclohexyl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (9 mg, 21.5 μmol, 56.2%) as a white solid. MS (M+H)+=420 (100% purity); 1H NMR (DMSO-d6) δ: 9.02 (s, 1H), 8.34-8.45 (m, 2H), 8.07 (d, J=2.3 Hz, 1H), 7.69 (d, J=9.4 Hz, 1H), 7.29 (dd, J=9.3, 2.5 Hz, 1H), 4.14 (s, 3H), 4.01-4.10 (m, 1H), 3.88 (s, 3H), 3.05 (d, J=3.8 Hz, 1H), 1.50-1.82 (m, 6H), 1.40 (br. s., 2H).

Aufarbeitung

  1. concentrationthen concentrated
  2. dissolutionThe residue was re-dissolved in 5 mL of a solution of (dichloromethane/MeOH/ammonium hydroxide; 60:10:1)
  3. stirringstirred at 25° C. for 3 h
  4. customevaporated to a light yellow solid
  5. dissolutiondissolved in dichloromethane (added few drops MeOH and heating)
  6. custompurified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
  7. washeluting with 0 to 10% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane
  8. dissolutionThe pure product dissolved in hot MeOH
  9. waitto stand overnight for solid formation
  10. customThe solid was separated by decantation
  11. customdried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-6f97487b57994b1e9b95b7a682668184
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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