4-(N,N-DIMETHYLSULPHONAMIDO)BENZENEBORONIC ACID

To a stirring solution of N, N-dimethyl-4-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2- yl)benzenesulfonamide (1.00 g, 2.25 mmol) in THF (20 mL) and water (5 mL) at 0 C was added sodium periodate (2.06 g, 9.64 mmol). The mixture was stirred for 5 min at this temperature and then allowed to warm to rt and stirred for a further 30 min. Aqueous HCl (1 M; 1.57 mL, 1.57 mmol) was added and the resulting mixture stirred at rt for a further 1 h. The reaction mixture was diluted with water (30 mL) and extracted with EtOAc (20 mL x 3). The organic layers were then combined and washed (brine), dried (Na2SO4) and concentrated in vacuo. The crude material was purified by flash column, eluting with 50% EtOAc/hexane followed by 10% MeOH in 50% EtOAc/hexane to afford (4-(N, N-dimethylsulfamoyl)phenyl)boronic acid (470 mg, 91%) as a brown solid.1H-NMR (300 MHz; CD3OD) d ppm: 2.69 (6H, s), 7.75 (2H, d, J = 8.2 Hz), 7.88-7.98 (2H, m).To a stirring solution of (Z)-tert-butyl (3-fluoro-4-((2-hydroxyphenyl)thio)but-2-en-1- yl)carbamate (150 mg, 0.48 mmol), Hi) Preparation of ethyl 3-[4-(dimethylsulfamoyl)phenyl]-7-isopropyl- 1 H-indole-2-carboxylate (1182) [00196] A mixture of ethyl 3-iodo-7-isopropyl-1 H-indole-2-carboxylate (250 mg, 0.7 mmol), [4- (dimethylsulfamoyl)phenyl]boronic acid (192.39 mg, 0.84 mmol), 2M Na2C03 (1 .4 ml) and Pd(dppf)CI2 (25.61 mg, 0.03 mmol) in dioxane (6.2 mL) was purged with argon then subjected to microwave irradiation at 100 C for 2 h. The resulting mixture was filtered over celite, rinsing with EtOAc and water. The filtrate was partitioned between EtOAc and 1 M HCI and the aqueous phase further extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (Telos 12 g, EtOAc in heptane, 0-50%) to give the title compound. (1183) [00197] NMR (400 MHz, CHLOROFORM-d) delta ppm 9.01 (1 H, br. s.) 7.88 (2 H, d, J=8.28 Hz) 7.75 (2 H, d, J=8.28 Hz) 7.44 (1 H, d, J=8.03 Hz) 7.26 - 7.33 (3 H, m) 7.14 - 7.24 (1 H, m) 4.33 (2 H, q, J=7.19 Hz) 3.35 (1 H, dquin, J=13.74, 6.92, 6.92, 6.92, 6.92 Hz) 2.70 - 2.88 (6 H, m) 1 .41 - 1 .53 (6 H, m) 1 .18 - 1 .32 (3H, m).To a stirred solution of 16 (150mg, 0.347mmo1) and 182 (79.5mg, 0.347mmo1) in acetonitrile (5mL), degassed and purged with nitrogen for 10mm, was added cesium carbonate (226mg, 0.695mmo1) and Pd(dppf)C12 (14mg, 0.0173mmo1), again degassed and purged with nitrogen for 15mm and the RM heated to 85C for 4hr in a sealed tube. After completion of the reaction the RIVI was cooled to rt and diluted with chloroform and filtered through celite bed. The organic layer was completely distilled off to get the crude product, which was passed through 100-200 mesh silica gel eluting the pure compound at 5% ethyl aceate in hexane as off white colored solid compound 183.

Molecular Weight:229.07
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:229.0580092
Monoisotopic Mass:229.0580092
Topological Polar Surface Area:86.2
Heavy Atom Count:15
Complexity:290
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes