4-(2-BroMoethyl)Morpholine HydrobroMide

Treat a solution of triphenylphosphine dibromide (124 g, 293 mmol) in DCM (2.44 L) with a solution of 4-morpholineethanol (32 g, 244 mmol) in DCM (60 mL) dropwise over one hour while maintaining the reaction temperature below 25° C. Stir the mixture overnight at room temperature. Conduct an additional reaction as above starting with 4-morpholineethanol (10 g, 76 mmol), scaling the reagents appropriately. Combine the reaction mixtures and collect the solids by vacuum filtration to give the title compound 76.7 g (84percent). Under nitrogen, at 0 ° to a solution of 2-morpholino ethanol (4g, 30.49mmol) in dichloromethane (80mL) was added portionwise dibromo-triphenylphosphine (15.45g, 36.59mmol). The mixture was stirred for 18 hours at 15 degreesTime. After completion of the reaction, the reaction mixture was filtered, the filter cake washed with dichloromethane and dried under reduced pressure to give off white solid (5.1g, 60.8percent).Under the protection of argon, Compound 87-1 (55 mg, 0.152 mmol) Soluble in anhydrous N, N-dimethylformamide (6mL), Add sodium tert-butoxide (44 mg, 0.457 mmol), 4- (2-Bromoethyl) morpholine hydrobromide (51 mg, 0.183 mmol) was dissolved in anhydrous N, N-dimethylformamide (1 mL), Added dropwise to the above system, Stir for 1.5 hours at room temperature. After the reaction is complete, Add water (15ml) to the system, The aqueous phase was extracted with ethyl acetate (10 mL x 2), Combined organic phases, The organic phase was washed with water (10 mL x 3) and saturated brine (10 mL x 1). Dried over anhydrous sodium sulfate, The solvent was distilled off under reduced pressure, The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate / dichloromethane = 2: 1: 1-1: 2: 2), Compound 87 (yellow solid, 50 mg) was obtained:Under the protection of argon, Compound 54 (50 mg, 0.145 mmol) was dissolved in anhydrous N, N-dimethylformamide (7 mL), Add sodium tert-butoxide (42 mg, 0.434 mmol), 4- (2-Bromoethyl) morpholine hydrobromide (48 mg, 0.174 mmol) was dissolved in anhydrous N, N-dimethylformamide (1 mL), Added dropwise to the above system, Stir for 1.5 hours at room temperature. After the reaction was completed, water (15 ml) was added to the system, and the aqueous phase was extracted with ethyl acetate (10 mL x 2). The organic phases were combined. The organic phases were washed with water (10 mL x 3) and saturated brine (10 mL x 1). Dry over anhydrous sodium sulfate and evaporate the solvent under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate / dichloromethane = 2: 1: 1-1: 2: 2) to obtain compound 86 (yellow solid, 28 mg):To a rt solution of 7-(l-(tetrahydro-2H-pyran-2-yl)-lH-pyrazol-5-yl)-2H- pyrazolo[3, 4-c]quinolin-4-amine (16.3 mg, 0.049 mmol) in DMF (162 pl) was added cesium carbonate (47.6 mg, 0.146 mmol) followed by 4-(2-bromoethyl)morpholine, hydrobromide (14.7 mg, 0.054 mmol). The suspension was stirred at rt for 16 h. The reaction was diluted with H2O (2 mL) and extracted with EtOAc (3 x 2 mL). The combined organic layers were concentrated. The crude material was mixed with CH2CI2 (200 pL) and TFA (200 pL) and stirred at rt for 1.5 h. The reaction was concentrated in vacuo. The crude material was dissolved in DMF (2 mL), filtered (syringe filter), and purified via preparative LC/MS with the following conditions: Column: XBridge C18, 200 mm x 19 mm, 5-pm particles; Mobile Phase A: 5:95 acetonitrile: water with l0-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with l0-mM ammonium acetate; Gradient: a 0-minute hold at 6% B, 6-46% B over 20 minutes, then a 4-minute hold at 100% B; Flow Rate: 20 mL/min; Column Temperature: 25 C. Fraction collection was triggered by MS signals. Fractions containing the desired product (the more polar of the two observedCompound 7-1 (250 mg, 1.13 mmol), 4- (2-bromoethyl) morpholine hydrobromide (372 mg, 1.35 mmol), Cesium carbonate (1.1g, 3.38mmol) is dissolved in 5ml DMF, Stir overnight at room temperature. The next day, after the reaction was detected by TLC, water was added for extraction, and the organic layer was washed with water and saturated brine in that order, and dried over anhydrous sodium sulfate. Suction filtration, the filtrate was concentrated under reduced pressure, the crude product was separated by column chromatography, 340 mg of colorless oil was obtained, Yield 90%.Cool a mixture of 2-(2-chloropyrimidin-4-yl)-6, 6-dimethyl-5H-thieno[2, 3- c]pyrrol-4-one hydrochloride (10 g, 32 mmol) and tetrabutylammonium iodide (1.17 g, 3.16 mmol) in N-methylpyrrolidone (211 mL) to 0 C using an ice water bath. Add sodium hydride (60 wt% in mineral oil, 5.06 g, 126.5 mmol) in portions. Stir the mixture at 0 C for 10 minutes and then add

Molecular Weight:274.98
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:274.93434
Monoisotopic Mass:272.93639
Topological Polar Surface Area:12.5
Heavy Atom Count:10
Complexity:73.5
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes