3-amino-5-(4-chlorophenyl)-2-thiophenecarboxylic acid

EPO 6-(4-Chlorophenyl)-3-[2-(dimethyIamino)-l-methyl-lET-benzimidazol-6-yl]thieno[3, 2- d\ [l, 2, 3]triazin-4(3H)-one; a) 3-Amino-5-(4-chIorophenyI)thiophene-2-carboxylic acid; Methyl 3-armno-5-(4-chlorophenyl)thiophene-2-carboxylate (2.00 g, 7.47 mmol) was refluxed in a solution of potassium hydroxide (2.0 g, 36 mmol) in 50 mL of water and 50 mL of methanol for 2 h. Methanol was evaporated and the residue was diluted to the double volume with water and washed with ethyl acetate. The aqueous layer was acidified with NaHSO6(4-Chlorophenyl)-3-{4-[2-(3-hydroxypyrrolidin-l-yI)ethoxy]-3- methoxyphenyl}thieno[3, 2-rf][l, 2, 3]triazin-4(3i)-one; a) 3-Amino-5-(4-chIorophenyl)thiophene-2-carboxylic acid; Methyl 3-amino-5-(4-chlorophenyl)thiophene-2-carboxylate (2.00 g, 7.47 rnmol) was refluxed in a solution of potassium hydroxide (2.0 g, 36 mmol) in 50 mL of water and 50 mL of methanol for 2 h. Methanol was evaporated and the residue was diluted to the double volume with water and washed with ethyl acetate. The aqueous layer was acidified with NaHSO EPO 6-(4-Chlorophenyl)-3-[2-(dimethyIamino)-l-methyl-lET-benzimidazol-6-yl]thieno[3, 2- d\ [l, 2, 3]triazin-4(3H)-one; a) 3-Amino-5-(4-chIorophenyI)thiophene-2-carboxylic acid; Methyl 3-armno-5-(4-chlorophenyl)thiophene-2-carboxylate (2.00 g, 7.47 mmol) was refluxed in a solution of potassium hydroxide (2.0 g, 36 mmol) in 50 mL of water and 50 mL of methanol for 2 h. Methanol was evaporated and the residue was diluted to the double volume with water and washed with ethyl acetate. The aqueous layer was acidified with NaHSO6(4-Chlorophenyl)-3-{4-[2-(3-hydroxypyrrolidin-l-yI)ethoxy]-3- methoxyphenyl}thieno[3, 2-rf][l, 2, 3]triazin-4(3i)-one; a) 3-Amino-5-(4-chIorophenyl)thiophene-2-carboxylic acid; Methyl 3-amino-5-(4-chlorophenyl)thiophene-2-carboxylate (2.00 g, 7.47 rnmol) was refluxed in a solution of potassium hydroxide (2.0 g, 36 mmol) in 50 mL of water and 50 mL of methanol for 2 h. Methanol was evaporated and the residue was diluted to the double volume with water and washed with ethyl acetate. The aqueous layer was acidified with NaHSOGeneral procedure: To a solution of the 5-aryl-3-amino-2-carboxylicacid (III) (5.28 mmol) in THF (50 mL) a solution of phosgene (6.10 mL, 20 wt% in toluene, 11.6 mmol) was added dropwise over a period of 30 min. The reaction mixture was stirred for 2 h at room temperature, followed by the addition of saturated aqueous solution of NaHCO3 (30 mL) and H2O (50 mL). The resulting mixture was extracted with EtOAc/THF (1:1, 3 100 mL). The organic layer was washed with saturated aqueous NaCl (100 mL), dried (MgSO4) and concentrated. The crude material was suspended in a mixture of n-hexane/EtOAc (2:1, 50 mL) heated to 50 C and after cooling to room temperature separated via filtration.

Molecular Weight:253.71
XLogP3:3.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:252.9964274
Monoisotopic Mass:252.9964274
Topological Polar Surface Area:91.6
Heavy Atom Count:16
Complexity:269
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes