4-Bromo-1-tosyl-1H-pyrrolo[2,3-b]pyridine

4-Bromo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2, 3-b]pyridine [D003] (0202) 4-Bromo-7-azaindole (3 g, 15.22 mmol) was weighed into a round bottom flask and dissolved in THF (50 mL) under nitrogen. The reaction mixture was cooled to 0° C. and treated portionwise with sodium hydride (60percent in mineral oil, 0.67 g, 16.75 mmol), the addition was accompanied by fizzing. After the addition the reaction mixture was allowed to stir for 30 minutes at room temperature and then treated with benzenesulfonyl chloride (2.14 mL, 16.75 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 2 hours. The reaction mixture was evaporated under reduced pressure and dissolved in DCM 30 mL, the organics were washed with 2×30 mL portions of 2M sodium carbonate, dried with MgSO4, filtered and evaporated to an orange oil. Purified by flash column chromatography eluting with 1:9 ethyl acetate:cyclohexane to provide the title compound as an off white solid (92percent). LCMS method: 5, RT 5.36 min, MI 337 [M+H]; NMR: (1H, 500 MHz, CDCld) Sodium hydroxide (31.4 ml, 188.35 mmol) was added to 4-bromo-1H-pyrrolo[2, 3-b]pyridine (10.03 g, 50.91 mmol), tosyl chloride (19.41 g, 101.81 mmol) and tetrabutylammonium hydrogensulfate (0.519 g, 1.53 mmol) in DCM (250 ml) at RT. The resulting mixture was stirred at RT for 1 hour. The reaction was quenched through the addition of saturated aqueous NHToluenesulfonyl chloride (219.0 g, 1.126 mol) and tetrabutylammonium hydrogen sulphate (9.8 g, 28.0 mmol) were added to a solution of 4-bromo-1 H-pyrrolo[2, 3-b]pyridine (which may be prepared as described in Org Letts, 2003, 5, 5023) (1 11.0 g, 0.563 mol) in DCM (2.8 L). To this was then added dropwise over 30 min a solution of sodium hydroxide (67.56 g, 1.59 mol) in water (281.2 mL), and the resultant reaction mixture was stirred at room temperature for 4 h. Water (562 mL) was then added, the organic phase was separated, washed with water (2 x 562 mL), dried (NaAqueous NaOH (6N, 5 mL) was added to a solution of 4-bromo-1H-pyrrolo[2, 3- jpyridine (1.6 g, 8.1 mmol), TsCI (3.1 g, 2.0 mmol) and BuAqueous NaOH (6N, 5 mL) was added to a solution of 4-bromo-1H-pyrrolo[2, 3-b]pyridine (1.6 g, 8.1 mmol), TsCl (3.1 g, 2.0 mmol) and BuStep A. 4-Bromo- 1 -tosyl- lH[2, 3-b]pyridine (A) was prepared by modification of the procedure described by Thibault, C. Org. Lett. 5(26):5023-5025, 2003, using tosyl choloride. Specifically, a solution of 4-bromo-lH-pyrrolo[2, 3-.pound.]pyridine (2.7g, 13.7 mmol)in DMF (40 mL) was treated with 60percent NaH (0.55g, 13.7 mmol) at OA solution of Intermediate lB-a (0.47 g, 1.49 mmol), Intermediate 40A (0.5 g, 1.42 mmol), Pd2(dba)3 (0.065 g, 0.071 mmol), XPhos (0.068 g, 0.142 mmol), potassium carbonate (0.59 g, 4.27 mmol) in toluene (10 mL) was stirred at 95C for 24 h. The reaction mixture was filtered through Celite. The solution, diluted with ethyl acetate (50 mL) was washed with water (50 mL). The product was extracted into ethyl acetate (2 x 50 mL). The combined extracts were dried (Na2S04) and evaporated. The residue was chromatographed on a 25 g Si cartridge eluting with 0-100% ethyl acetate in iso hexane to give Intermediate 40B (0.273 g). LCMS (Method 9): Rt = 1.70 min, m/z 584.3 [M+H]+To a solution of N, N-diisopropylamine (1.8 g, 18.222 mmol) in anhydrous tetrahydrofuran (40 mL) under at nitrogen atmosphere at -78C was added 2.5M n-butyllithium (7.3 mL, 18.2 mmol) in hexanes dropwise. Stirred for 5 minutes, then added 4-bromo-1-(p-tolylsulfonyl)pyrrolo[2, 3-b]pyridine (4 g, 11.4 mmol) dissolved in anhydrous tetrahydrofuran (20 mL). Stirred at -78C for 30 minutes. To the solution was then added 3-oxetanone (1.6 g, 22.8 mmol) and continued to stir at -78C for one hour. Allowed the solution to warm to ambient temperature and stirred there for 2 hours. Quenched with saturated ammonium chloride (50 mL). Attempted to extract with ethyl acetate, however a solid remained suspended in both layers. Filtered mixture through filter paper, separated organic layer, dried with Na2S04, filtered and concentrated onto silica. The mixture was purified by column chromatography eluting with a gradient of 0-40% ethyl acetate in hexanes. Pure fractions were combined and concentrated to yield the title compound (2.06 g, 43%).(R)-6-Methyl-3-(4-(isopropylsulfonyl)phenyl)-4, 5, 6, 7-tetrahydropyrazolo[1, 5-a]piperazine (307 mg , 0.96mmol),

Molecular Weight:351.22
XLogP3:3.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:349.97246
Monoisotopic Mass:349.97246
Topological Polar Surface Area:60.3
Heavy Atom Count:20
Complexity:443
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes