1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid

4.2.23 4.2.23 1-(Phenylsulfonyl)-1H-pyrrolo[2, 3-b]pyridine-2-carboxylic acid (17) In a heat dried and nitrogen purged tricol round bottom flask, 5 (1.05 g, 4.07 mmol) was solubilized in dry THF (15 mL), cooled to -35 C then lithium diisopropylamide (5.1 mL, 10.16 mmol, 2 M) was added slowly. The mixture was then cooled to -55 C and dry ice was added slowly. The mixture was left to warm up to room temperature under stirring overnight. The reaction was quenched with water and extracted with EtOAC. The aqueous layer was acidified by the addition of a 6 N hydrochloric acid solution to pH = 1 and extracted with EtOAC. The latter organic layer was washed with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 1.09 g of the expected product as a beige solid in 88% yield. 1H NMR (300 MHz, DMSO-d6) delta (ppm): 13.87 (br, 1H), 8.51 (dd, J = 1.6, 4.7 Hz, 1H), 8.26 (d, J = 7.0 Hz, 2H), 8.13 (dd, J = 1.6, 7.9 Hz, 1H), 7.77 (dd, J = 7.2 Hz, 1H), 7.72-7.65 (m, 2H), 7.39 (dd, J = 4.7, 7.9 Hz, 1H), 7.28 (s, 1H). 13C NMR (75 MHz, DMSO-d6) delta (ppm): 164.4, 149.5, 147.3, 138.5, 135.1, 133.3, 132.1, 129.8 (2C), 128.3 (2C), 121.1, 120.7, 112.5.To a stirred solution of l -(phenylsulfonyl)-lH-pyrrolo[2, 3- )]pyridine-2-carboxylic acid (3.60 g, 11.9 mmol) in DMF (30 mL) was added DIPEA (6.24 mL, 35.7 mmol), HATU (6.79 g, 17.8 mmol) and dimethylamine (8.9 mL, 17.8 mmol). Resulting reaction mixture was allow to stir at room temperature for 16 h. The reaction mixture was poured in ice water (50 mL) and extracted with ethyl acetate (3 x 30 mL), organic layer washed with water (3 x 50 mL), brine (2 x 30 mL). The combined organic layer was dried over Na2S04 and concentrated to obtain the title compound (4 g) as an off white solid. LC-MS retention time = 0.64 min; m/z = 330.4 [M+H]+. Column: ACQUITY BEH C8 (2.1 x 50mm) 1.7 mu: Flow: 0.7 mL/min; Mobile Phase A: 0.1% TFA in water; Mobile Phase B: 0.1% TFA in ACN; 2% B to 98% B over 1.0 min., then hold a 0.6 min. at 98% B of flow rate 0.7 ml/min; Detection: UV at 220 nm.General procedure: (Method A) To a suspension of 18f (1.16 g, 5.74 mmol) in DMF (10 ml) was added CDI (973 mg, 6 mmol) and then the mixture was stirred at room temperature for 40 min. To the mixture was added sodium cyanamide (845 mg, 13.1 mmol), followed by stirring at room temperature for 1 h. The mixture was then diluted with H2O, and the pH was adjusted to 6.1 with 2 M/L hydrochloric acid, and the precipitated solid was filtered. The solid obtained was suspended in MeOH and the pH was adjusted to 6.1 with 1 M/L MeONa/MeOH, and then evaporated to give compound 19f (1.33 g, 93%) as a solid.

Molecular Weight:302.31
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:302.03612798
Monoisotopic Mass:302.03612798
Topological Polar Surface Area:97.6
Heavy Atom Count:21
Complexity:496
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes