Trifluoroacetic acid → 2-(2-methyl-3-(piperidin-4-ylamino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1055884Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1055884
[CH3:1][C:2]1[C:3]([NH:22][CH:23]2[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[C:12]1[NH:20][C:19]2[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=2[CH:13]=1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:1][C:2]1[C:3]([NH:22][CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[N:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][C:6]=2[C:12]2[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=2)[N:11]=1

Komponenten

5

Edukt 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 89793635tert-butyl 4-((3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxalin-2-yl)amino)piperidine-1-carboxylate

Produkt 1

HCID 897834662-(2-methyl-3-(piperidin-4-ylamino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneAusbeute 6,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of tert-butyl 4-((3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxalin-2-yl)amino)piperidine-1-carboxylate (Ex. 47, 80 mg, 0.168 mmol) in DCM (1.7 mL) was stirred at 25° C. before adding TFA (12.47 μl, 0.168 mmol, Sigma Aldrich). The resulting solution was stirred for 30 min before carefully adding saturated aq. NaHCO3 (10 mL) and stirring for an additional 30 min. The reaction mixture was then concentrating under reduced pressure, and the residue was taken up in DMSO and purified by reverse-phase preparative HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 80%). The product-containing fractions were concentrated under reduced pressure, and the residue was loaded onto a pre-washed (MeOH, 1 volume) functionalized Si-carbonate column (Silicyle) and allowed to percolate through, providing 2-(2-methyl-3-(piperidin-4-ylamino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (4.3 mg, 6.8%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.92 (1H, s) 7.83-7.91 (1H, m) 7.52-7.58 (2H, m) 7.28-7.35 (1H, m) 7.11-7.16 (1H, m) 3.98-4.11 (3H, m) 3.41-3.49 (2H, m) 2.97-3.06 (2H, m) 2.89 (2H, s) 2.59-2.71 (2H, m) 2.54 (3H, s) 1.93-2.04 (2H, m) 1.43-1.59 (2H, m). m/z (ESI, +ve) 377.1 (M+H)+.

Aufarbeitung

  1. concentrationThe reaction mixture was then concentrating under reduced pressure
  2. custompurified by reverse-phase preparative HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 80%)
  3. concentrationThe product-containing fractions were concentrated under reduced pressure
  4. washa pre-washed (MeOH, 1 volume) functionalized Si-carbonate column (Silicyle)

Quellen und Nachweise

ORD-Eintrag
ord-043b9d277f1a44a8a6392e26ad46e03b
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394297B2

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