methyl 3-(aminomethyl)benzoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (R)-3-((6-(3-(2-ethoxyphenoxy)piperidin-1-yl)nicotinamido)methyl)benzoic acid was prepared from (R)-6-(3-(2-ethoxyphenoxy)piperidin-1-yl)nicotinic acid and methyl 3-(aminomethyl)benzoate using Amidation Method 1 (HATU) and Ester Hydrolysis Method 1 (LiOH). 1H NMR (500 MHz, CD3OD) δ 8.84 (app t, 1H), 8.58 (d, 1H), 8.02 (s, 1H), 7.92 (dd, 2H), 7.58 (d, 1H), 7.44 (t, 1H), 7.01 (d, 1H), 6.92 (m, 2H), 6.87 (m, 1H), 6.73 (d, 1H), 4.60 (m, 2H), 4.37 (m, 1H), 4.05 (dd, 1H), 3.93 (m, 2H), 3.72 (m, 3H), 2.07 (m, 1H), 1.95 (m, 2H), 1.59 (m, 1H), 1.28 (t, 3H). MS (ES+) 476.3 (M+H).

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (R)-3-((6-(3-(2-ethoxyphenoxy)piperidin-1-yl)nicotinamido)methyl)benzoic acid was prepared from (R)-6-(3-(2-ethoxyphenoxy)piperidin-1-yl)nicotinic acid and methyl 3-(aminomethyl)benzoate using Amidation Method 1 (HATU) and Ester Hydrolysis Method 1 (LiOH). 1H NMR (500 MHz, CD3OD) δ 8.84 (app t, 1H), 8.58 (d, 1H), 8.02 (s, 1H), 7.92 (dd, 2H), 7.58 (d, 1H), 7.44 (t, 1H), 7.01 (d, 1H), 6.92 (m, 2H), 6.87 (m, 1H), 6.73 (d, 1H), 4.60 (m, 2H), 4.37 (m, 1H), 4.05 (dd, 1H), 3.93 (m, 2H), 3.72 (m, 3H), 2.07 (m, 1H), 1.95 (m, 2H), 1.59 (m, 1H), 1.28 (t, 3H). MS (ES+) 476.3 (M+H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Phenyl-furan-2-carboxylic acid (6) (17 mg, 0.10 mmol) was coupled to 3-aminomethyl-benzoic acid methyl ester (19.4 mg, 0.10 mmol) using Method D to give the title compound

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 20% solution of piperidine in DMF (5 ml) was added to 3-[(9H-Fluoren-9-ylmethoxycarbonylamino)-methyl]-benzoic acid methyl ester (193 mg, 0.5 mmol) and the reaction was stirred at room temperature for 30 min. Water (10 ml) was added to the crude reaction mixture, followed by 1M HCl (10 ml). The aqueous layer was washed with EtOAc (3×10 ml) then basified to pH 9 with saturated NaHCO3. The basic layer was extracted with EtOAc (3×10 ml) and the aqueous layer was evaporated down to a small volume, then further extracted with EtOAc (5×10 ml). The combined organic layers were dried (MgSO4), filtered and the solvent evaporated in vacuo to give the title compound. reaction mixture The aqueous layer was washed with EtOAc (3×10 ml) The basic layer was extracted with EtOAc (3×10 ml) the aqueous layer was evaporated down to a small volume further extracted with EtOAc (5×10 ml) The combined organic layers were dried (MgSO4) filtered the solvent evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Phenyl-furan-2-carboxylic acid (6) (17 mg, 0.10 mmol) was coupled to 3-aminomethyl-benzoic acid methyl ester (19.4 mg, 0.10 mmol) using Method D to give the title compound

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 20% solution of piperidine in DMF (5 ml) was added to 3-[(9H-Fluoren-9-ylmethoxycarbonylamino)-methyl]-benzoic acid methyl ester (193 mg, 0.5 mmol) and the reaction was stirred at room temperature for 30 min. Water (10 ml) was added to the crude reaction mixture, followed by 1M HCl (10 ml). The aqueous layer was washed with EtOAc (3×10 ml) then basified to pH 9 with saturated NaHCO3. The basic layer was extracted with EtOAc (3×10 ml) and the aqueous layer was evaporated down to a small volume, then further extracted with EtOAc (5×10 ml). The combined organic layers were dried (MgSO4), filtered and the solvent evaporated in vacuo to give the title compound. reaction mixture The aqueous layer was washed with EtOAc (3×10 ml) The basic layer was extracted with EtOAc (3×10 ml) the aqueous layer was evaporated down to a small volume further extracted with EtOAc (5×10 ml) The combined organic layers were dried (MgSO4) filtered the solvent evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Phenyl-furan-2-carboxylic acid (6) (17 mg, 0.10 mmol) was coupled to 3-aminomethyl-benzoic acid methyl ester (19.4 mg, 0.10 mmol) using Method D to give the title compound

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 20% solution of piperidine in DMF (5 ml) was added to 3-[(9H-Fluoren-9-ylmethoxycarbonylamino)-methyl]-benzoic acid methyl ester (193 mg, 0.5 mmol) and the reaction was stirred at room temperature for 30 min. Water (10 ml) was added to the crude reaction mixture, followed by 1M HCl (10 ml). The aqueous layer was washed with EtOAc (3×10 ml) then basified to pH 9 with saturated NaHCO3. The basic layer was extracted with EtOAc (3×10 ml) and the aqueous layer was evaporated down to a small volume, then further extracted with EtOAc (5×10 ml). The combined organic layers were dried (MgSO4), filtered and the solvent evaporated in vacuo to give the title compound. reaction mixture The aqueous layer was washed with EtOAc (3×10 ml) The basic layer was extracted with EtOAc (3×10 ml) the aqueous layer was evaporated down to a small volume further extracted with EtOAc (5×10 ml) The combined organic layers were dried (MgSO4) filtered the solvent evaporated in vacuo