6-BROMO-2-HYDROXY-3-METHOXYBENZALDEHYDE

NSC95682 is an IRE-1α inhibitor with an IC50 of 0.08 μM, extracted from patent WO 2008154484 A1, IRE-lα inhibitor compound 3-5.

2-Acetoxy-3-methoxy-6-bromo-benzaldehyde (48.2 g, 176.5 mmol)Soluble in methanol (500mL), Slowly add 6N hydrochloric acid (500 mL), The reaction was stirred at room temperature overnight and suction filtered.After washing the filter cake with petroleum ether (100×3), The filter cake was sucked dry in vacuo to give a yellow solid (40.4g, 99percent).2-Hydroxy-3-methoxy-6bromo-benzaldehyde (12). Compound 11 (11.44g, 41 . 89mmol) is dissolved in the methanol aqueous solution (84 ml), by adding NaHCOThe compound of formula 11 (11.44 g, 41.89 mmol) was dissolved in aqueous methanol (84 mL) and NaHCO3 (4.93 g, 58.64 mmol)The resulting cloudy solution was stirred at room temperature for 2 hours, the plate was detected until the reaction was complete, acidified with hydrochloric acid, The mixture was extracted with dichloromethane (3 × 80 mL). The organic phases were combined, washed with saturated NaCl solution, dried over anhydrous sodium sulfate, filtered, The solvent was distilled off under reduced pressure. Recrystallization from ethyl acetate and n-hexane gave 8.23 g of the compound of formula 12 as yellow crystals with a yield of 85percent.Take a 100 mL clean round bottom flask.Add 10mL of water, In the fume hood, With a gas mask, Carefully add bromine (0.99 g, 6.18 mmol), Potassium bromide (1.23 g, 10.30 mmol) was then added.Stir for 5min, After stirring evenly, 12 (1.0 g, 5.15 mmol) was added in small portions.Be careful to add 12 slowly.Allow the ingredients to mix evenly in the solution, An orange-red insoluble matter was formed, and the reaction was carried out at 20 ° C, and the reaction was monitored by TLC. After 24 h, the solution was reddish brown insoluble and the reaction continued. After 48 hours, the TLC test has basically completed the reaction. The insoluble precipitate was filtered, and the precipitate was washed with water (10 mL×3). After the reddish brown solid was dried, 1.2 g of crude product was obtained, and the residue was crystallized from ethyl acetate (1 mL).93.5percent.

Molecular Weight:231.04
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:229.95786
Monoisotopic Mass:229.95786
Topological Polar Surface Area:46.5
Heavy Atom Count:12
Complexity:162
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes