Boron trifluoride etherate → HCID 178517054, compound

Participants

Reaction Conditions

Reaction Steps

A dry-round bottom was charged with (E)-3-((3-((E)-2-(pyridin-4-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)methylene)indolin-2-one (906 mg, 1.83 mmol), and CH2Cl2 (100 mL) under an atmosphere of N2. Boron trifluoride etherate (2.3 mL, 18.3 mmol) was added dropwise and the reaction was stirred for 4 hours at which time LC-MS indicated complete conversion to the partially de-protected material (E)-3-((1-(hydroxymethyl)-3-((E)-2-(pyridin-4-yl)vinyl)-1H-indazol-6-yl)methylene)-indolin-2-one. The CH2Cl2 was removed in vacuo, and then 150 mL of a 2:1 mixture of EtOH/2M HCl was added and the reaction heated to 50° C. for 3 hours at which time LC-MS indicated complete conversion to the title compound. The reaction was cooled with an ice-bath and neutralized with NH4OH to pH˜8, the EtOH was removed and the suspension filtered washing with water. The dried solid was collected and then titurated and filtered several times with 90:10 CH2Cl2/MeOH which gave, after drying, the title compound (353 mg, 53%) as an orange solid. 1H NMR (400 MHz, d6-DMSO) δ 13.57 (s, 1H), 10.64 (s, 1H), 8.57 (d, J=5.16 Hz, 2H), 8.38 (d, J=8.13 Hz, 1H), 7.92 (s, 1H), 7.87 (d, J=16.7 Hz, 1H), 7.80 (s, 1H), 7.71 (d, J=5.16 Hz, 2H), 7.62-7.53 (m, 3H), 7.23 (t, J=8.29 Hz, 1H), 6.91-6.82 (m, 2H); MS ESI 365.1 [M+H]+, calcd for [C23H16N4O+H]+ 365.14.

Provenance & Evidence