6-(Phenylmethyl)-5H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione

Off-White Solid

General procedure: These compounds were prepared using the same procedure as reported above, but at 150°C for 18–26h. Following work up, the crude products were purified on 15cm×2.5cm silica gel columns eluted with 60–80percent EtOAc in hexanes. The isolated yields are given in Table 3. Note: Saturated NHIn a flask 120g2, 3- pyridinedicarboxylic acid, 110g of acetic anhydride, heated up with stirring, the solid is gradually dissolved, and when the internal temperature reached 92 deg.] C, all the solid had dissolved, 92 ~ 95 temperature control for 2 to 3 hours to 2, 3-pyridyl acid ≤0.1percent, the reaction was completed, cooling to 50 ~ 60 , evaporated under reduced pressure, heated to 80 ~ 85 , no flow to continue evaporated under reduced pressure, cooling to 50 ~ 60 , toluene was added 40g , mixing temperature, the toluene was evaporated to dryness under reduced pressure, 40g of toluene and then once with the above-described method, steaming complete, 169g of toluene was added, heated to 40 ~ 50 stir, cooled to 30 ~ 40 benzylamine was slowly added dropwise 92.3g dropping process control temperature does not exceed 55 , 2 hours drop end, at a temperature of 40 ~ 50 for 3 to 4 hours to pyridine-2, 3-dicarboxylic acid anhydride ≤0.1percent, the reaction was completed, water bath heating, external temperature control 85 evaporated to dryness under reduced pressure, the residue was added 110g acetic anhydride, heated up with stirring, the temperature control 92 ~ 95 for 1 to 2 hours to precipitate solid, and stirring was continued for 1 to 2 hours to ring-opened product ≤0.1percent, the reaction was completed, cooling to 50 ~ 60 distilled off under reduced pressure dry, warmed to 80 ~ 85 , no flow to continue distilled off under reduced pressure, temperature lowered to room temperature, was added 200mL95percent ethanol, cooled to 0 stirred for 5 hours, filtered, cooled to 5 cake was washed with 95percent ethanol and washed 28mLx3 three times, drained, dried in vacuo to give an off-white solid 6-benzyl-pyrrolo [3, 4-b] pyridine-5, 7-dione 150g, yield 88 ~ 90percentPreparation 646-Benzyl-5H-pyrrolo[3, 4-blpyridine-5, 7(6H)-dione; To 2-(benzylcarbamoyl)nicotinic acid (Preparation 63) (202.7 g, 0.789 mol) was added acetic anhydride (30OmL), toluene (30OmL) and trifluoro-acetic acid (3OmL) successively. Then the mixture was heated to 100-110To 1000 ml three-necked flask were added 148 g pyrrolo[3, 4-b]pyridine-5, 7-dione (1.0 mol) and 500 ml of N, N-dimethylformamide was dissolved, 110 g of triethylamine was added (1.1 mol) was heated to 40 °C, was slowly added dropwise 188 g of benzyl bromide (1.1 mol), stirred at 40 °C incubated for 2 hours, the reaction compound into a dark brown liquid, TLC tracking reaction when raw pyrrolo[3, 4-b]pyridine-5, 7-dione completion of the reaction, the reaction mixturewas cooled to room temperature with stirring, the reaction mixture was cooled as slowly poured into 500 ml of cold water, alarge number of off-white solid immediately precipitated, was filtered, The filter cake was washed with cold water, and driedovernight at 60 °C under vacuum to give 214 g white powder in a yield of 90percent.Preparation 31 : 6-Benzyl-5H-pyrrolo[3, 4-b]pyridine-5, 7(6H)-dione.Benzylamine (3.85 ml, 35.2 mmol) was added to a suspension of 2, 3-pyridinedicarboxylic anhydride (5 g, 33.5 mmol), in acetic acid (50 ml), and the mixture was heated under reflux for 18 hours. It was then cooled to room temperature, concentrated in vacuo and the residue was triturated with diethyl ether to afford the title compound as a white solid in 57percent yield, 4.52 g. 1HNMR(400MHz, CDCI3) δ: 4.79(s, 2H), 7.27(m, 1H), 7.32(m, 4H), 7.78(dd, 1H), 8.29(d, 1H), 8.96(d, 1H); LRMS APCI m/z 239 [M+H]+A solution of compound 6a (5.0 g, 33.6 mol) and compound 6b (3.9 g, 36.9 mmol) in AcOH (60 ml) was refluxed overnight. The reaction was concentrated and purified by silica gel chromatography (eluting with petroleum ether/EtOAc=10:1~3:1) to give compound 6c (4.5 g, yield:56percent). 1H NMR (400MHz, CHLOROFORM-d) δ= 8.16 (dd, J=1.3, 7.7 Hz, 1H), 7.61 (dd, J=5.0, 7.7 Hz, 1H), 7.46 (d, J=6.8 Hz, 2H), 7.36 - 7.31 (m, 3H), 7.29 (d, J=6.6 Hz, 2H), 4.92 (s, 2H)Pyridine-2, 3-dicarboxylic acid (10.0 g, 59.9 mmol) and acetic anhydride (15 mL) were added successively to toluene (20 mL) in the three-necked flask and the mixture was stirred at 110 °C for 3 h. After cooling to room temperature, sodium acetate (0.1 g) was added and benzylamine (7.05 g, 65.9 mmol) was dropped in below 45 °C with stirring. The mixture was retained at 45 °C for 1 h and acetic anhydride (10 mL) was poured in with stirring for 2 h under reflux. The solvent was removed under vacuum and water (40 mL) was added with stirring for 30 min. After filtration, the precipitate was washed with water (3×20 mL) and ethanol (3×10 mL) respectively and it was dried at 50 °C under vacuum to give the title compound (12.0 g, 84.2percent yield)

Molecular Weight:238.24
XLogP3:1.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:238.074227566
Monoisotopic Mass:238.074227566
Topological Polar Surface Area:50.3
Heavy Atom Count:18
Complexity:350
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes