2-AMINO-4,5,6,7-TETRAHYDRO-BENZO[B]THIOPHENE-3-CARBOXYLIC ACID

2M Aqueous NaOH solution (91 mL, 182 mmol) was added to a suspension of 2-amino-4, 5, 6, 7- tetrahydro-benzo[B]thiophene-3-carboxylic acid methyl ester [108354-78-5] (13.1 g, 60.8 mmol) in EtOH (100 mL). The reaction mixture was heated to 60 C and stirred for 4 h. The temperature was raised to 80 C (reflux) and the reaction was stirred overnight. The reaction was left stirring at 80 C for a further 7 h and was then cooled to r.t. and stirred overnight. The reaction mixture was concentrated in vacuo to remove the EtOH. The aqueous solution was washed with DCM (3 x 200 mL) and then acidified to pH 2 with concentrated hydrochloric acid. A brown solid was formed which was filtered off, washed with water, then hexane and dried to afford the title compound (7.55 g, 63%) as a dark brown solid. dH (400 MHz, DMSO -d6) 11.8 (br. s, 1H), 7.16 (s, 2H), 2.57 - 2.61 (m, 2H), 2.40 - 2.44 (m, 2H), 1.63 - 1.72 (m, 4H).EDCI (5.0 g, 26 mmol) was added to a solution of intermediate 112 (4 g, 20.28 mmol), 1- hydroxybenzotriazole hydrate (3.52 g, 22.3 mmol), DIPEA (14.5 mL, 83.2 mmol) and 2M solution of methylamine in THF (31 mL, 62 mmol) in DMF (100 mL) and the reaction was stirred overnight. The reaction mixture was concentrated in vacuo and the residue was partitioned between EtOAc (100 mL) and water (100 mL) and the organic layer was separated. The organic layer was washed with brine (2 x 100 mL), filtered to remove an insoluble dark brown solid, dried (Na SC> ), filtered and concentrated in vacuo. The crude product was dissolved in DCM and purified by flash column chromatography on silica (gradient elution with 10% - 40% EtOAc in /so-hexane). The product was recrystallised from EtOAc/ /so-hexane to afford the title compound (1.32 g, 31%) as a brown solid. 6H (300 MHz, DMSO -d6) 6.67 - 6.73 (m, 1H), 6.64 (s, 2H), 2.68 (d, J 4.6 Hz, 3H), 2.53 - 2.58 (m, 2H), 2.42 - 2.47 (m, 2H), 1.62 - 1.74 (m, 4H).

Molecular Weight:197.26
XLogP3:2.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:197.05104977
Monoisotopic Mass:197.05104977
Topological Polar Surface Area:91.6
Heavy Atom Count:13
Complexity:222
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes