反应详情

4-{[(2,4-Dimethoxybenzyl)(1,3-thiazol-2-yl)amino]sulfonyl}benzoic acid (Preparation 99, 1.30E3 mg, 0.00300 mol), HBTU (1400.8 mg, 0.0031671 mol) and Et3N (1.07 mL, 0.00766 mol) were mixed in methylene chloride (10 mL, 0.2 mol). 4-tert-butylbenzylamine (424.1 mg, 0.002598 mol) was added and the reaction stirred overnight. The reaction was washed with saturated sodium bicarbonate (aq) followed by 0.5N HCl. The organic phase was separated and dried over magnesium sulfate, then treated with activated carbon and filtered through a Celite pad. The solvent was removed in vacuo to give an oily residue. The residue was triturated with DCM and the solid collected by filtration. LCMS analysis of the solid revealed cleavage of the dimethoxybenzyl protection group had occurred. The gray solid was saved. The filtrate was purified by column chromatography, chloroform to 10% MeOH in chloroform gradient eluent. Product fractions were combined and evaporated to an oily residue. The residue was triturated with methylene chloride and beige solid collected. The solid products from steps 4 and 5 were combined and dissolved in 1N NaOH (aq). The solution was washed 3× with diethyl ether. The basic aqueous phase was treated with activated carbon and filtered through a Celite pad. The pale yellow filtrate was slowly acidified to pH 2-3 with 6N HCl (aq). The resultant precipitate was collected by filtration. Vacuum drying yielded 511 mg of product as a white powder.

1. washThe reaction was washed with saturated sodium bicarbonate (aq)
2. customThe organic phase was separated
3. dry with materialdried over magnesium sulfate
4. additiontreated with activated carbon
5. filtrationfiltered through a Celite pad
6. customThe solvent was removed in vacuo
7. customto give an oily residue
8. customThe residue was triturated with DCM
9. filtrationthe solid collected by filtration
10. customThe filtrate was purified by column chromatography, chloroform to 10% MeOH in chloroform gradient eluent
11. customevaporated to an oily residue
12. customThe residue was triturated with methylene chloride and beige solid
13. customcollected
14. dissolutiondissolved in 1N NaOH (aq)
15. washThe solution was washed 3× with diethyl ether
16. additionThe basic aqueous phase was treated with activated carbon
17. filtrationfiltered through a Celite pad
18. filtrationThe resultant precipitate was collected by filtration
19. customVacuum drying