5-BROMO-1H-PYRROLO[2 , 3-B]PYRIDIN-2(3H)-ONE

Pink powder

To a solution of compound 25 (5.64 g, 15.2 mmol) in Acetic acid (AcOH, 100 mL) Zn power (9.88 g, 0.15 mmol) was added. [0105] Zinc dust (24.7 g, 377.73 mmol) was added in portions to a stirred solution of 3, 3, 5-tribromo-1, 3-dihydro-2H-pyrrolo[2, 3-b]pyridin-2-one (Preparation 1a, 14 g, 37.75 mmol) in 288 ml acetic acid and the reaction was stirred overnight at room temperature. Solvent was removed and crude was basified with saturated aqueous sodium hydrogencarbonate solution and it was extracted with chloroform/methanol 9:1, organic layer was dried (Na5-Bromo-1, 3-dihydro-pyrrolo [2, 3-b] pyridin-2-one (4) Zinc dust (34.0 g, 0.52 mol) was added in small portion to a stirred suspension of 3 (40.85 g, 0.111 mol) in glacial acetic acid (1000 mL) at such a rate that the temperature was maintained between 20-25 °C (strongly exothermic reaction; external ice bath cooling). Addition took about 20 min. Cooling bath was removed and stirring was continued at r. t. for 2 h. The solid was filtered off, washed with toluene (50 mL) and triturated with CH2Cl2 : MeOH=4: 1 (2.5 L). The solution was decanted off and treated with 1.0 M aqueous Na2C03 solution (170 mL). After stirring for 1 h the two layers were separated. The organic layer was washed again with 1.0 M aqueous Na2C03 solution (50 mL). The combined aqueous layers were extracted with CH2Cl2 : MeOH=4: 1 (10x100 mL). Combined organic solutions were dried with MgS04 (200 g) and concentrated. The residual solid was dissolved in THF (2000 mL) and insoluble material was filtered off. The filtrate was concentrated to dryness in vacuum to afford 4 (16.93 g, 72percent) as tan solid. 1H NMR (400 MHz, DMSO-d6) 8 3.57 (s, 2H), 7.75 (m, 1H), 8. 14 (m, 1H), 11.13 (bs, 1H).5-Bromo-1, 3-dihydro-pyrrolo [2, 3-b] pyridin-2-one (4); Zinc dust (34.0 g, 0.52 mol) was added in small portion to a stirred suspension of 3 (40.85 g, 0.111 mol) in glacial acetic acid (1000 mL) at such a rate that the temperature was maintained between 20-25 °C (strongly exothermic reaction; external ice bath cooling). Addition took about 20 min. Cooling bath was removed and stirring was continued at r. t. for 2 h. The solid was filtered off, washed with toluene (50 mL) and triturated with CH2Cl2 : MeOH=4: 1 (2.5 L). The solution was decanted off and treated with 1.0 M aqueous Na2CO3 solution (170 mL). After stirring for 1 h the two layers were separated. The organic layer was washed again with 1.0 M aqueous Na2CO3 solution (50 mL). The combined aqueous layers were extracted with CH2Cl2 : MeOH=4: 1 (10x100 mL). Combined organic solutions were dried with MgS04 (200 g) and concentrated. The residual solid was dissolved in THF (2000 mL) and insoluble material was filtered off. The filtrate was concentrated to dryness in vacuum to afford 4 (16.93 g, 72percent) as tan solid. 1H NMR (400 MHz, DMSO-d6) 8 3.57 (s, 2H), 7.75 (m, 1H), 8.14 (m, 1H), 11.13 (bs, 1H).To a solution of 3, 3, 5-tribromo-lH-pyrrolo[2, 3-b]pyridin-2(3H)-one (5 g, 13.48 mmol) in HOAc (100 mL) was added Zn (8.82 g, 134.8 mmol) under 2 atmosphere. The reaction was stirred at rt for 5 h, then filtered through a pad of Celite, which was washed with DCM/MeOH (10/1 (v/v), 55 mL). The filtrate was washed with HUnder nitrogen protection, A solution of 3, 3, 5-tribromo-1H-pyrrolo [2, 3-b] pyridine-2 (3H) -one (5 g, 13.48 mmol)Was dissolved in acetic acid (100 mL)To this was added zinc dust (8.82 g, 134.8 mmol).The reaction solution was stirred at room temperature for 5 hours and then filtered through celite, The filter cake was washed with a mixture of dichloromethane / methanol (10/1 (v / v), 55 mL).The filtrate was collected, washed with water (50 mL)The aqueous phase was extracted with a mixture of dichloromethane / methanol (10/1 (v / v), 55 mL x3). The combined organic phases were dried with anhydrous sodium sulfateDried, filtered and concentrated under reduced pressure. The residue was washed with dichloromethane (20 mL x 3) to give the title compound as a red solid (1.62 g, 56.4percent).To a solution of 3, 3, 5-tribromo-lH-pyrrolo[2, 3-b]pyridin-2(3H)-one (20 g, 53.93 mmol) in acetic acid (150 mL) was added zinc dust (17.64 g, 269.67 mmol). The reaction mixture was stirred at RT for 5 h and subsequently concentrated to dryness in vacuo. The residue was diluted with ethyl acetate (200 mL) and washed with water. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to dryness in vacuo to afford 5-bromo-lH-pyrrolo[2, 3-b]pyridin-2(3H)-one (4.6 g, 40percent): NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 8.16 (s, 1H), 7.77 (s, 1H), 3.58 (s, 2H).Step 2: 5-bromo-lH-pyrrolo[2, 3-b]pyridin-2(3H)-one To a solution of 3, 3, 5-tribromo-lH-pyrrolo[2, 3-b]pyridin-2(3H)-one (20 g, 53.93 mmol) in acetic acid (150 mL) was added zinc dust (17.64 g, 269.67 mmol). The reaction mixture was stirred at RT for 5 h and subsequently concentrated to dryness in vacuo. The residue was diluted with ethyl acetate (200 mL) and washed with water. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to dryness in vacuo to afford 5-bromo-lH-pyrrolo[2, 3-b]pyridin-2(3H)- one (4.6 g, 40percent): H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 8.16 (s, 1H), 7.77 (s, 1H), 3.58 (s, 2H).To a solution of 3, 3, 5-tribromo-1, 3-dihydro-pyrrolo[2, 3-b]pyridin-2-one (25 gm, 67.4 mmol) in AcOH (500 ml-purged with nitrogen for 40 min) was added zinc (43.91 gm, 675.5 mmol). In 1000 ml flask is added in 200 ml ethanol, the 1H - pyrrolo [2, 3 - the b] pyridine (5.9 g, 50 mmol) dissolved wherein adding 30percent ofHb) General procedure: To a screw cap vial was added osylhydrazone (1.0 mmol) in 1, 4 Dioxane (5.0 mL). Thencharged etraethylammonium bromide (1.0 mmol) followed by the addition of DBU (2.5 mmol)and Mo(CO)6 (1.0 mmol) at room temperature. The mixture was heated to 110°C for 1.0 h. Thereaction progress was monitored by using TLC. After consumption of starting material thereaction mixture was filtered through celite bed and washed with ethyl acetate. The ethyl acetatelayer was washed with water and brine. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure to afford crude compound. The crudecompound was purified by flash column chromatography on Biotage instrument using 4.0 g snapcartridge and eluted with ethyl acetate in hexane to give oxindole.

Molecular Weight:213.03
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:211.95853
Monoisotopic Mass:211.95853
Topological Polar Surface Area:42
Heavy Atom Count:11
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes