Hydrochloric Acid → HCID 68458454, compound

Participants

Reaction Steps

Following the procedure of Example 2, but substituting (R)-tert-butyl 2-(bromomethyl)pyrrolidine-1-carboxylate for 4-(2-chloroethyl)morpholine, (R)-tert-butyl 2-((5-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-1H-indazol-1-yl)methyl)pyrrolidine-1-carboxylate (22 mg, 8%) was prepared as a yellow powder. A solution of this compound (22 mg, 0.044 mmol) in CH2Cl2 (2 mL) was treated with trifluoroacetic acid (25 mg, 0.22 mmol). After stirring at room temperature for 16 h, the reaction mixture was diluted with EtOAc (10 mL) and washed with 1N NaOH (10 mL). The organics were dried (Na2SO4), filtered and concentrated. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH/NH4OH, 40:1:0.1 to 20:1:0.2) provided the free base. This was dissolved in ethyl acetate (0.4 mL) and treated with 1 equivalent of 1 M HCl in Et2O and the mixture was filtered to provide the title compound (14.8 mg, 77%) as a yellow solid: 1H NMR (500 MHz, DMSO-d6) δ 9.25 (s, 1H), 9.01 (s, 1H), 8.25 (s, 1H), 7.86 (d, J=8.9 Hz, 1H), 7.79 (d, J=17 Hz, 1H), 7.60 (d, J=7.6 Hz, 1H), 7.49-7.35 (m, 6H), 6.12 (dd, J=7.6, 2.6 Hz, 1H), 5.99 (d, J=2.7 Hz, 1H), 5.16 (s, 2H), 4.85-4.71 (m, 2H), 4.02-3.92 (m, 1H), 3.32-3.22 (m, 1H), 3.20-3.11 (m, 1H), 2.14-2.05 (m, 1H), 2.02-1.92 (m, 1H), 1.91-1.85 (m, 1H), 1.78-1.68 (m, 1H); ESI MS m/z 401 [M+H]+.

Provenance & Evidence