The fresh new solvent is eliminated not as much as quicker tension, drinking water is additional plus the resulting mix is extracted that have EtOAc

General procedure for the preparation of benzamides 2, cuatro, and 21–23: 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.

This new solvent is actually evaporated lower than smaller stress therefore the ensuing rough unit refined because of the line chromatography for the SiO

Ethyl 3-(3,4-dimethoxy-benzamido)benzoate (2): Compound 2 was synthesized according to the general procedure by using 19 (0.05 g, 0.28 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), 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.