Hydrochloric Acid → 3,4-Dihydro-1H-isoquinoline-2-carboxylic Acid [4-(2-amino-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amide

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A 2 mL aliquot of tert-butyl {2-[4-({[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}amino)-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]ethyl}carbamate in dimethylformamide (60.0 μmol) was added to 1,2,3,4-tetrahydroisoquinoline (9.59 mg, 1.2 eq) and stirred at room temperature for 18 hr. To this was added 2.0M hydrochloric acid in ether (150 μL, 5 eq) and the reaction was stirred at room temperature for 60 hr. Some of the deprotections were incomplete so 2-3 drops of concentrated hydrochloric acid was added to these and they were stirred for another 24 hr. The ether and hydrochloric acid were evaporated under a stream of nitrogen and it was purified by HPLC. The proper fractions were collected and lyophilized to afford the title compound as a white solid in 42.9% yield. LCMS m/z (%)=392 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.85 (t, J=5.81 Hz, 2H), 3.09-3.17 (m, 2H), 3.69 (t, J=5.6 Hz, 2H), 3.69 (s, 3H), 4.12 (t, J=5.56 Hz, 2H), 4.63 (s, 2H), 6.32 (d, J=2.02 Hz, 1H), 7.13 (d, J=9.09 Hz, 1H), 7.19 (s, 3H), 7.43 (d, J=2.53 Hz, 1H), 7.47 (d, J=1.52 Hz, 1H), 7.57 (dd, J=9.09, 3.03 Hz, 1H), 7.87 (s, 2H), 8.60 (s, 1H).

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