2-CHLORO-6-FLUOROBENZYL BROMIDE

Colorless to dark yellow liquid

At room temperature, compound 26-d (300 mg, 1.03 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL), zinc powder (203 mg, 3.1 mmol) and 6-chloro-2-fluorobenzyl bromide (693 mg, 3.1 mmol) were added into the reaction solution. The reaction mixture was heated to 55C and stirred for 1 hour. After cooling down to room temperature, saturated ammonium chloride solution (20 mL) was added to quench the reaction. After extraction with EtOAc (50 mL*2), the organic phases were combined and washed successively by water (50 mL) and saturated brine (50 mL), dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (PE:EtOAc=5:1) to give a white solid 31-c (325 mg, yield: 81%). LC-MS (ESI): m/z = 389[M+1]+.At room temperature, To a stirred solution of methyl-2-methyl-3-oxo-i, 2, 3, 4-tetrahydroquinoxaline-6- carboxylate (Preparation 5) (0.2 g, 0.91 mmol) in dry DMF (5.0 mL) was added K2C03 (0.25 g, 1.82 mmol) followed by To a stirred solution of methyl-i, 2-dimethyl-3-oxo-i, 2, 3, 4-tetrahydrobenzo- [e][i, 2, 4]triazine-6-carboxylate (Preparation 1) (0.045 g , 0.19 mmol) in DMF (1.5 mL) was added NaH (4.82 mg, 0.20 mmol, 60% suspension in oil) at 0-5 C under an inert atmosphere and the whole allowed to stir for 20-30 min., before 2-chloro-6- fluorobenzyl bromide (0.02 mL, 0.21 mmol) was added dropwise with cooling and the reaction mass was then stirred at room temperature for 2 h. The course of the reaction was monitored by TLC and/ or LCMS. After completion of the reaction the mixture was quenched with a saturated solution of NH4Cl, diluted with water and extracted with EtOAc. The combined organics were washed with brine twice, dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to give the title compound methyl-4-(2-chloro-6-fluorobenzyl)-i, 2-dimethyl-3-oxo-i, 2, 3, 4-tetrahydrobenzo[e] [i, 2, 4]triazine-6 carboxylate (0.07 g, 97% yield, purity >95%) as an off white solid. The product was used in the next step without any further purification. LCMS m/z: 378.09 (M+H).General procedure: Dichloromethane (10 mL) and triethylamine (1.1 mmol) wereadded to 100mL round-bottom flask. Then 23 (1.0 mmol) indichloromethane (20 mL) was added dropwise. The mixture wasstirred for 15 min at room temperature, then 1-(bromomethyl)-3-chlorobenzene (1.0 mM) was added. The reaction was stirred atroom temperature overnight. Then the mixture was poured into50 mL of brine and was extracted with dichloromethane. Theorganic layer was dried over anhydrous sodium sulfate, and thecrude compound was purified by column chromatography to givethe desired compound 24a.

Molecular Weight:223.47
XLogP3:3.2
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:221.92472
Monoisotopic Mass:221.92472
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes