Synthesis of N-(2-Aminophenyl)-4-(thiophen-2-yl)benzamide

Example 15

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Step 1:

Compound 1 (100 mg, 0.62 mmol), tert-butyl 2-amino-4-(thiophen-2-yl)phenylcarbamate (151 mg, 0.52 mmol), HOAt (141 mg, 1.04 mmol), EDCI (200 mg, 1.04 mmol), and Et₃N (0.2 mL) were combined in THE (5 mL), and the reaction was stirred at rt overnight. After completed, the mixture was concentrated and the crude was carried over for next step (300 mg, crude).

Step 2:

The crude Compound 2 (300 mg, crude) and TFA (3 mL) were combined in DCM (6 mL). The reaction was stirred at rt for 2 h. The mixture was purified by Prep-HPLC (base method). White solid was afforded to obtain compound 018 (130 mg, 43%, 2 steps). LCMS: m/z=334.8 (M+H)⁺. ¹H NMR (400 MHz, DMSO) δ 9.77 (s, 1H), 8.39 (d, J=33.4 Hz, 2H), 7.90 (d, J=7.6 Hz, 1H), 7.71 (s, 1H), 7.51 (s, 1H), 7.39-7.21 (m, 3H), 7.07 (dd, J=13.2, 9.0 Hz, 1H), 6.83 (d, J=8.2 Hz, 1H).