8-Bromoisoquinoline

Yellow powder

A mixture of 2-bromobenzaldehyde (50 g, 270 mmol) , aminoacetaldehyde dimethyl acetal (28.4 g, 270 mmol) and toluene (400 mL) was refluxed under argon. Dehydration was carried out using dean stark for 2.0 hours. After removal of calculated amount of water, the reflux was continued for 1.0 hour. The toluene was evaporated under reduced pressure, the residue was dissolved in dichloromethane (600 mL) , and the solution was cooled to 0°C. To the cooled solution was slowly added aluminium chloride (118.9 g, 891.7 mmol) under argon. The reaction mixture was stirred at 45°C for 2.0 hours. After the completion of the reaction was confirmed by TLC, the mixture was cooled to room temperature and slowly poured into an ice water. The mixture was basified with 10percent sodium hydroxide solution, and the dichloromethane layer was separated. The aqueous layer was re-extracted with dichloromethane (2 x 100 mL) . The combined dichloromethane layers were washed with brine, and dried over sodium sulfate. The dichloromethane was evaporated, and the residue was purified by silica gel (100-200 mesh) column chromatography 5 with 8-12percent. ethyl acetate in hexane as a mobile phase to give the title compound as an off-white solid (28 g, 49.8percent). MS(ESI)m/z: 208 [M (A solution of Example 8; To a cold (0 0C), stirred solution of 18 (3.34 g) in CHCI3 (35 ml_) was added mCPBA (5.54 g of 77percent) in one portion. The cold bath was removed and the mixture was stirred at RT for 3 h before being quenched with a saturated aqueous solution of Na2CO3. The organic layer was separated and the aqueous layer was extracted with CH2CI2 (2 x 30 ml_). The combined organic layers were dried over Mg2SO4, filtered, and concentrated under vacuum to yield A/-oxide 19 which was directly used in the next step without further purification.Preparation of S1. Prepare 8 g of Compound 17 (30 mg, 0.085 mmol), General procedure: A suspension of intermediate 15(104.0 mg, 0.4 mmol), 7-bromoquinoline (124.8 mg, 0.6 mmol), t-BuONa (96.0 mg, 1.0 mmol), Pd2(dba)3 (18.0 mg, 0.019 mmol) andX-phos (9.6 mg, 0.02 mmol) in PhMe (2.8 ml) was degassed under astream of nitrogen over 10 min. The mixture was heated to 110 Cand stirred overnight. The resulting mixturewas filtered off and thesolution was concentrated under vacuum. The crude product waspurified by column chromatography on silica using a solvent of 60%ethyl acetate in hexanes. Compound 3l was obtained as a lightgreen solid (Yield: 60.0 mg, 38.8%).

Molecular Weight:208.05
XLogP3:2.8
Hydrogen Bond Acceptor Count:1
Exact Mass:206.96836
Monoisotopic Mass:206.96836
Topological Polar Surface Area:12.9
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes