6-Chlorobenzo[b]thiophene-2-carboxylic acid

To a solution of 600 mg (3.23 mmol) of 4-chloro-2-nitro-benzaldehyde in DMF (7 ml) were added 559 mg (4.04 mmol) of potassium carbonate and 294 μl (3.23 mmol) of methyl thioglycolate at 0° C. The reaction mixture was stirred for 30 min at 0° C. and then for 24 h at RT. Then the mixture was poured into ice-water and the precipitate was collected by filtration and dissolved in ethyl acetate. The solution was dried (MgSOTo a solution of compound B-101 (10 g, 44 mmol) in tetrahydrofuran (200 mL) and water ( 10 mL) was added lithium hydroxide monohydrate (5.6 g, 0.13 mol). The reaction mixture was stirred at room temperature overnight. On completion, the reaction mixture was concentrated in vacuo to remove tetrahydrofuran and poured into water (400 mL). The pH was adjusted to 3 with 4M hydrochloric acid, resulting in formation of a solid. The solid was collected by filtration, washed with water and dried in vacuo to give compound B-102 (5.6 g, 60percent yield) as a white solid. LCMS: (ESTo a solution of ethyl 6-chlorobenzothiophene-2-carboxylate Xl-9a (9.00 g, 37.5 mmol) inEtOH was added 3 N NaOH (24.9 ml, 74.7 mmol) and the reaction mixture was stirred at20 room temperature for 16h. Progress of the reaction was monitored by TLC. Aftercompletion, the reaction mixture was concentrated under vacuum. The residue wasdiluted with H20 (200 ml), acidified with 2 N HCI and extracted with EtOAc (2 x 300 ml).The organic layer was separated, dried over anhydrous Na2S04 and concentrated undervacuum to afford 6-chlorobenzothiophene-2-carboxylic acid Xl-9b (6.1 0 g) as an off-whitesolid.This compound was used as such for the next reaction without further purification.Yield: 77percent5 1H NMR (400 MHz, DMSO-d5) o 8.00 (d, J=8.31 Hz, 2H) 8.10 (s, 1 H) 8.21 (s, 1 H) 13.52(brs, 1 H).To a solution of [000924] Compound 242C (420 mg, 1.98 mmol) and copper powder (63 mg, 0.99 mmol) were suspended in quinoline (10 mL) and the resulting mixture was heated at 185 C for 2 h. After cooling down to room temperature, ethyl acetate (25 mL) was added and the suspension was filtered. The filtered cake was washed with ethyl acetate (5 mL x 2) and the combined organic layers were washed with aqueous HC1 solution (2 N, 10 mL x 2). After drying over anhydrous sodium sulfate, the solution was filtered and evaporated in vacuo to give a residue. The crude product was purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, from 0% to 10% v/v) to afford Compound 242D.A representative list of such carboxylic acids includes: ... 4-(4-methoxy-phenyl)-benzoic acid 5-methoxy-indol-2-yl-carboxylic acid General procedure: To a solution of 3a-3o (1.94 mmol) in anhydrous dichloromethane(20.0 mL) and HATU (2.33 mmol) in the presence of DIEA(3.89 mmol), tert-butylpiperazine-1-carboxylate (2.14 mmol) wasadded and stirred for 12 h. After completion, dilute hydrochloricacid solution was added, extracted with dichloromethane andwashed with saturated sodium carbonate solution three times. Thecombined organic layers were washed with brine and dried with sodium sulfate, filtered, concentrated, and purified by silica gelchromatography with petroleum ether/ethyl acetate as eluent togive pure 4a-4o [34].

Molecular Weight:212.65
XLogP3:3.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:211.9698783
Monoisotopic Mass:211.9698783
Topological Polar Surface Area:65.5
Heavy Atom Count:13
Complexity:222
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes