* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With sodium hydroxide In water at 35℃; for 1.5 h; Heating / reflux
Stage 1 - 1 ,3-Dibromo-5-methoxy-2-methylbenzeneDimethyl sulfate (4.6 mL, 48 mmol) was added dropwise to a suspension of 3,5- dibromo-4-methylphenol (10.64 g, 40 mmol) and NaOH (2.08 g, 52 mmol) in water (50 mL) at such a rate as to maintain the temperature of the reaction mixture below 35 0C. After completion of the addition the reaction mixture wax refluxed for 1.5 hours. The reaction mixture was allowed to cool to room temperature and extracted with EtOAc (3x50 mL). The combined organic extracts were washed with a 2N NaOH solution (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated under reduced pressure to leave a yellow solid. Purification by column chromatography (10 percent EtOAc in heptane) afforded the title compound as a white solid (9.35 g, 83 percent yield). 1H NMR (300 MHz, CDCI3) 7.11 (2H1 s), 3.78 (3H, s), 2.51 (3H, s).
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; hexanes-Et2O;
Step A: 2,6-Dibromo-4-methoxy-benzyl bromide To a suspension of 5.0 g of <strong>[14542-71-3]2,6-dibromo-4-methoxytoluene</strong> in 90 mL of CCl4 was added N-bromosuccinimide and benzoyl peroxide. The resulting mixture was heated to reflux and stirred at the refluxing temperature while irradiating with a sunlamp for 2 h, then cooled and concentrated. The resulting residue was dissolved in 1:1 hexanes-Et2O and filtered through a pad of silica gel, then purified by flash chromatography on a Biotage 40M column, eluding with 98:2 hexanes-Et2O, to yield 2,6-Dibromo-4-methoxy-benzyl bromide as a pale yellow solid. IH NMR (500 MHz, 2,6-Dibromo-4-methoxy-benzyl bromide as a pale yellow solid. 1H NMR (500 MHz,
7-(1-<i>tert</i>-butyl-1,2,3,6-tetrahydro-pyridin-4-yl)-5-(2-chloro-4-fluoro-phenyl)-1-(2,6-dichloro-phenyl)-3,4-dihydro-1<i>H</i>-quinazolin-2-one[ No CAS ]
4-[5-(2-chloro-phenyl)-1-(2,6-dichloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-quinazolin-7-yl]-3,6-dihydro-2<i>H</i>-pyridine-1-carboxylic acid <i>tert</i>-butyl ester[ No CAS ]
4-[5-(2-chloro-phenyl)-1-(2,6-dichloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-quinazolin-7-yl]-piperidine-1-carboxylic acid <i>tert</i>-butyl ester[ No CAS ]
4-[5-(2-chloro-4-fluoro-phenyl)-1-(2,6-dichloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-7-yl]-piperidine-1-carboxylic acid <i>tert</i>-butyl ester[ No CAS ]
4-[1-(2,6-dichloro-phenyl)-5-(2,4-difluoro-phenyl)-2-oxo-1,2,3,4-tetrahydro-quinazolin-7-yl]-piperidine-1-carboxylic acid <i>tert</i>-butyl ester[ No CAS ]
4-[5-(2-chloro-4-fluoro-phenyl)-1-(2,6-dichloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-quinazolin-7-yl]-piperidine-1-carboxylic acid <i>tert</i>-butyl ester[ No CAS ]
4-[5-(2-chloro-4-fluoro-phenyl)-1-(2,6-dichloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-quinazolin-7-yl]-3,6-dihydro-2<i>H</i>-pyridine-1-carboxylic acid <i>tert</i>-butyl ester[ No CAS ]
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane;
Intermediate 19 To a solution of 1,3-dibromo-5-methoxy-2-methyl-benzene (16.50 g, 58.9 mmol) in 300 mL of anhydrous CCl4 under a nitrogen atmosphere was added N-bromosuccinimide (12.59 g, 70.7 mmol) and benzoyl peroxide (1.57 g, 6.5 mmol). The solution was then heated to reflux. Once the solution reached reflux it was irradiated with a 250 W sun lamp. After 3.5 h the solution was cooled to RT and concentrated. To the residue was added ca. 50 mL DCM and the resulting suspension filtered. The filtrate was purified by silica gel chromatography (450 g SiO2) using 5% DCM in hexanes as the eluent to give 2-bromomethyl-1,3-dibromo-5-methoxy-benzene. 1H NMR(CDCl3, 500 MHz): delta3.81 (s, 3 H), 4.83 (s, 2 H), 7.13 (s, 2 H). MS(ES) 277 (M-Br); LC 1: 3.93 min.
With sodium hydroxide; In water; at 35.0℃; for 1.5h;Heating / reflux;
Stage 1 - 1 ,3-Dibromo-5-methoxy-2-methylbenzeneDimethyl sulfate (4.6 mL, 48 mmol) was added dropwise to a suspension of 3,5- dibromo-4-methylphenol (10.64 g, 40 mmol) and NaOH (2.08 g, 52 mmol) in water (50 mL) at such a rate as to maintain the temperature of the reaction mixture below 35 0C. After completion of the addition the reaction mixture wax refluxed for 1.5 hours. The reaction mixture was allowed to cool to room temperature and extracted with EtOAc (3x50 mL). The combined organic extracts were washed with a 2N NaOH solution (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated under reduced pressure to leave a yellow solid. Purification by column chromatography (10 % EtOAc in heptane) afforded the title compound as a white solid (9.35 g, 83 % yield). 1H NMR (300 MHz, CDCI3) 7.11 (2H1 s), 3.78 (3H, s), 2.51 (3H, s).