Reaktion #333601

Reaktionsgleichung

sodium triacetoxyborohydride

N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-oxopropyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

3,3-difluoroazetidine hydrochloride

→

N-tert-butyl-2-(1-(3-(3,3-difluoroazetidin-1-yl)propyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Ausbeute 98.8%

Lösungsmittel

NaHCO3

dichloroethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for 18 h
3. 3
   Extraktionextracted with dichloromethane (5×20 mL)
4. 4
   TrocknenThe organic layer was dried (MgSO4)
5. 5
   Einengenconcentrated in vacuo
6. 6
   SonstigeThe resultant residue was purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
7. 7
   Wascheneluting with 0 to 5% over 20 min (MeOH containing 10% ammonium hydroxide)/dichloromethane

Vorschrift

To a solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-oxopropyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (34 mg, 58.0 μmol) in dichloroethane (6 mL) was added 3,3-difluoroazetidine hydrochloride (9.76 mg, 75.3 μmol.30). The mixture was stirred at 25° C. for 15 min, then sodium triacetoxyborohydride (18.4 mg, 86.9 μmol0) was added and stirring was continued for 18 h. The reaction mixture was diluted with saturated NaHCO3 solution and extracted with dichloromethane (5×20 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 5% over 20 min (MeOH containing 10% ammonium hydroxide)/dichloromethane to give N-tert-butyl-2-(1-(3-(3,3-difluoroazetidin-1-yl)propyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (38 mg, 57.2 μmol, 98.8%) as an off-white solid. MS (M+Na)+=686; 1H NMR (CDCl3) δ: 9.22 (s, 1H), 8.36 (s, 1H), 8.32 (d, J=2.3 Hz, 1H), 8.05 (s, 1H), 7.59 (d, J=9.1 Hz, 1H), 7.36 (dd, J=9.1, 2.3 Hz, 1H), 6.55 (t, J=74.0 Hz, 1H), 5.75 (s, 2H), 4.61 (t, J=6.6 Hz, 2H), 3.53-3.72 (m, 6H), 2.64 (t, J=6.0 Hz, 2H), 2.14 (dq, J=6.8, 5.7 Hz, 2H), 1.64 (s, 9H), 0.91-1.08 (m, 2H), 0.00 (s, 9H).

Quelle