General procedure for the preparation of benzamides 2, 4, and 21–2step three: To a mixture of the appropriate acid (1 equiv) and 20 (1 equiv) in CH2Cl2 (5 mL mmol ?1 ) was added HATU (1.2 equiv) and DIPEA (3 equiv) at 0 °C and after which it was stirred at 29 °C for 8 h. The combined organic layers were dried over anhydrous Na2SO4 and filtered. The EtOAc was evaporated under reduced pressure and the resulting crude product was purified by column chromatography over SiO2 (hexane/EtOAc as eluent) to afford the desired amides 2, 4, 21–23.
The newest solvent was evaporated lower than faster stress together with resulting crude device filtered by the column chromatography on SiO
Ethyl 3-(3,4-dimethoxy-benzamido)benzoate (2): Compound 2 was synthesized according to the general procedure by using 19 (0.05 g, 0.twenty-eight mmol) and was obtained as a yellow solid (0.63 g, 0.21 mmol, 76 %). 1 H NMR (400 MHz, CDCl3): ?=8.19–8.00 (m, 3H), 7.80 (d, J=7.5 Hz, 1H), 7.49 (s, 1H), 7.47–7.37 (m, 2H), 6.87 (d, J=8.4 Hz, 1H), 4.35 (q, J=7.1 Hz, 2H), 3.92 (s, 6H), 1.37 (t, J=7.0 Hz, 3H). 13 C NMR (101 MHz, CDCl3): ?=, , , , , , , , , , , , , , , , ; HRMS (ESI + ) [M+H] + C18NO5 calculated Da, found: m/z.
H20
Ethyl 3-(2-(3,4-dimethoxyphenyl)acetamido)benzoate (4): Compound 4 was synthesized according to the general procedure (but extracted with CH2Cl2 instead of EtOAc), using 2-(3,4-dimethoxyphenyl)acetic acid (0.20 g, 1.02 mmol) and was obtained as a yellow solid (0.28 g, 0.83 mmol, 81 %). 1 H NMR (500 MHz, CDCl3): ?=7.91–7.84 (m, 2H), 7.74 (d, J=7.7 Hz, 1H), 7.49 (d, J=7.2 Hz, 1H), 7.35 (t, J=7.8 Hz, 1H), 6.89–6.84 (m, 2H), 6.83 (s, 1H), 4.33 (q, J=7.1 Hz, 2H), 3.88 (s, 3H), 3.87 (s, 3H), 3.68 (s, 2H), 1.35 (t, J=7.1 Hz, 3H); 13 C NMR (126 MHz, CDCl3): ?=, , , , , , , , , , , , , , , , , ; HRMS (ESI + ) [M+H] + C19Htwenty-twoNO5 calculated Da, found: m/z.
Ethyl 3-(2,4-bis-(benzyloxy)benzamido)benzoate (21): Compound 21 was synthesized according to the general procedure, using 16 (0.06 g, 0.18 mmol) and was obtained as a brown solid (0.02 g, 0.04 mmol, 20 %). 1 H NMR (400 MHz, CDCl3): ?=9.92 (s, 1H), 8.30 (d, J=8.7 Hz, 1H), 7.94 (s, 1H), 7.71 (d, J=7.7 Hz, 1H), 7.61–7.21 (m, 12H), 6.77 (d, J=9.0 Hz, 1H) matchocean nedir, 6.73 (s, 1H), 5.19 (s, 2H), 5.14 (s, 2H), 4.37 (q, J=7.1 Hz, 2H), 1.39 (t, J=7.1 Hz, 3H).
Ethyl 3-(3,4-bis-(benzyloxy)benzamido)benzoate (22): Compound 22 was synthesized according to the general procedure using 17 (0.10 g, 0.30 mmol), but was not extracted. Instead the solvent of the reaction mixture was evaporated under reduced pressure and the residue directly purified by column chromatography. The desired product was obtained as a yellow solid (0.14 g, 0.28 mmol, 93 %). 1 H NMR (400 MHz, CDCl3): ?=8.09 (s, 1H), 8.03 (d, J=8.1 Hz, 1H), 7.99 (s, 1H), 7.80 (d, J=7.7 Hz, 1H), 7.55 (d, J=2.0 Hz, 1H), 7.48–7.27 (m, 12H), 6.93 (d, J=8.4 Hz, 1H), 5.21 (s, 2H), 5.19 (s, 2H), 4.36 (q, J=7.1 Hz, 2H), 1.38 (t, J=7.1 Hz, 3H).
Ethyl 3-(3,5-bis-(benzyloxy)benzamido)benzoate (23): Compound 23 was synthesized according to the general procedure (but extracted with CH2Cl2 instead of EtOAc), using 18 (0.17 g, 0.50 mmol) and was obtained as a white solid (0.09 g, 0.02 mmol, 36 %). m/z (ESI + ) [M+H] + C30H28NO5 calculated 482.2 Da, found: 482.8 m/z.
General procedure for the preparation of compounds 1,3, and 6 via O-benzyl-deprotection: To a mixture of the respective O-benzyl-protected compounds in THF/MeOH (1 : 1 v/v, 30 mL mmol ?1 ) was added palladium on active carbon (20 w%). The resulting suspension was stirred at room temperature for 8 h under H2 atmosphere (1 bar) and then filtered over Celite. 2 (hexane/EtOAc as eluent) to afford the desired compounds 1, 3 and 6.
