Hydrochloric Acid → HCID 68459790, compound

Participants

Reaction Steps

Following the procedure of Example 2, but substituting tert-butyl 2-(bromomethyl)morpholine-4-carboxylate for 4-(2-chloroethyl)morpholine, tert-butyl 2-((5-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-1H-indazol-1-yl)methyl)morpholine-4-carboxylate (134 mg, 33%) was prepared as a white powder. A solution of this compound (134 mg, 0.26 mmol) in CH2Cl2 (1 mL) was treated with trifluoroacetic acid (148 mg, 1.3 mmol). After stirring at room temperature for 16 h, the reaction mixture was diluted with CH2Cl2 (50 mL) and washed with 1N NaOH (50 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 (0.3 mL) and treated with 1 equivalent of 1 M HCl in Et2O and the mixture was filtrated to provide the title compound (68.2 mg, 58%) as a yellow solid: melting point (mp) 221-223° C. dec; 1H NMR (500 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.18 (s, 1H), 7.75-7.70 (m, 2H), 7.62 (d, J=7.6 Hz, 1H), 7.49-7.40 (m, 4H), 7.39-7.35 (m, 2H), 6.11 (dd, J=7.6, 2.7 Hz, 1H), 5.99 (d, J=2.7 Hz, 1H), 5.15 (s, 2H), 4.64-4.60 (m, 2H), 4.20-4.15 (m, 1H), 3.93-3.88 (dd, J=12.6, 3.3 Hz, 1H), 3.68-3.60 (m, 1H), 3.36-3.32 (m, 1H), 3.15 (d, J=12.6 Hz, 1H), 2.96-2.84 (m, 2H); ESI MS m/z 417 [M+H]+.

Provenance & Evidence