4,5-DICHLOROTHIOPHENE-2-CARBOXYLIC ACID

Compound 4(190 g, 0.9 mol) was dissolved in THF (1200 mL). Then 4 M LiOHaqueous solution (250 mL) was added celite, and concentrated giving4, 5-dichlorothiophene-2-carboxylic acid (170 g, 96percent) as to themixture. The solution was stirred 30 min at room temperature andthen THF was removed under reduced pressure. The residual aqueoussolution was acidified with 1 N hydrochloric acid and extracted threetimes with ethyl acetate. The combined organic phase was dried overMgSO4, decoloured with activated carbon, filtered through a whitesolid; m.p. 196–197 °C (lit.23 194–195 °C) IR (KBr): 1689 cm–1 (C=O).1H NMR (DMSO-d6): 13.48 (br s, 1H, COOH), 7.68 (s, 1H, H‑3).13C NMR (DMSO-d6): 161.5, 132.5, 132.3, 130.1, 124.6. Anal. calcd forC5H2C12O2S: C, 30.48; H, 1.02; found: C, 30.28; H, 1.15percent. MS (ESI):m/z 196.0 [M–H]–.A solution of i-Pr4, 5-Dichlorothiophene-2-carboxylic acid (162 mg, 0.82 mmol), EDC hydrochloric acid (157 mg, 0.82 mmol), HOBt (55 mg, 0.41 mmol) and DIPEA (0.23 mL, 1.26 mmol) were dissolved in DMF (5 mL). After 5 minutes of stirring, N1-(1-(5-bromo-1H-indol-2- yl)ethyl)propane- 1, 3 -diamine (120 mg, 0.41 mmol) was added, and it was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, and it was washed with 1N hydrochloric acid, 10% sodium hydroxide and brine. The organic layer was dried over sodium sulfate. The organic layer was concentrated under reduced pressure. The residue was purified on an ISCO chromatograph (0-10% methanol/dichloromethane + 0.1% NEEOH) to give the product as a white solid (63 mg, 32%);1H NMR (300 MHz) (CDCh) d 8.88 (bs, 1H), 7.64 (s, 1H), 7.26-7.12 (m, 3H), 7.06 (bs, 1H), 6.26 (s, 1H), 4.04-3.98 (m, 1H), 3.65-3.58 (m, 1H), 3.49-3.40 (m, 1H), 2.75-2.69 (m, 1H), 2.63-2.57 (m, 1H) 1.74-1.68 (m, 2H), 1.49 (d, J= 7 Hz, 3H); LC/MS RT = 3.05 (M+H+: 474/476/478).Weigh

Molecular Weight:197.04
XLogP3:3.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:195.9152559
Monoisotopic Mass:195.9152559
Topological Polar Surface Area:65.5
Heavy Atom Count:10
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes