反应详情

para-Toluenesulphonic acid (38 mg/0.20 mmol) and 3,4-dihydro-2H-pyran (2.75 mL/30.1 mmol) are added successively to a solution of 1-benzyl-6-[4-fluoro-3-(methoxycarbonyl)phenyl]-3-iodo-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (4.43 g/10.0 mmol) in 50 mL of DCM. The solution is stirred at ambient temperature for 12 hours. The reaction medium is run into a solution of KHSO4 (1 M) and extracted with EtOAc. The organic phase is washed with water and with a saturated aqueous solution of NaCl, dried over sodium sulphate, filtered and concentrated to dryness. The brown gum obtained is dissolved in 75 mL of DCM and added to the TEA scavenger resin (FL-TEA, Polymerlab, Variant, 3.53 mmol/g) (3.3 g/11 mmol). After stirring at ambient temperature for 2 h, the resin is filtered and washed with DCM. After drying under vacuum, the resin is then stirred for 20 minutes in a solution of triethylamine (2.6 mL/18 mmol) in 90 mL of DCM and then filtered and rinsed with DCM. The filtrate is acidified with a solution of KHSO4 (1 M). After extraction with EtOAc, the organic phase is washed with water and with a saturated aqueous solution of NaCl, dried over sodium sulphate, filtered and concentrated to dryness to give 4.3 g of an orange powder (yield: 82%).

1. extractionextracted with EtOAc
2. washThe organic phase is washed with water and with a saturated aqueous solution of NaCl
3. dry with materialdried over sodium sulphate
4. filtrationfiltered
5. concentrationconcentrated to dryness
6. customThe brown gum obtained
7. stirringAfter stirring at ambient temperature for 2 h
8. filtrationthe resin is filtered
9. washwashed with DCM
10. customAfter drying under vacuum
11. filtrationfiltered
12. washrinsed with DCM
13. extractionAfter extraction with EtOAc
14. washthe organic phase is washed with water and with a saturated aqueous solution of NaCl
15. dry with materialdried over sodium sulphate
16. filtrationfiltered
17. concentrationconcentrated to dryness