반응 #1779401

반응 방정식

formaldehyde

formaldehyde

Sodium triacetoxyborohydride

sodium triacetoxyborohydride

4-[2-(1-azetidin-3-yl-1H-pyrazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

dichloromethane

→

title compound

4-{4-Chloro-2-[1-(1-methylazetidin-3-yl)-1H-pyrazol-5-yl]phenoxy}-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

용매

methyl isobutyl ketone acetic acid water

ethyl acetate

반응 조건

후처리

1. 1
   기타at room temperature
2. 2
   기타for 15 minutes
3. 3
   workup.STIRRINGthe reaction stirred for 15 minutes
4. 4
   workup.STIRRINGstirred at room temperature for 3 hours
5. 5
   기타The mixture was evaporated
6. 6
   workup.DISSOLUTIONthe residue dissolved in ethyl acetate (20 mL)
7. 7
   세척washed with saturated aqueous sodium bicarbonate solution (2×10 ml) and saturated aqueous sodium chloride solution (2×10 ml)
8. 8
   기타The organic layer was separated
9. 9
   건조dried over sodium sulphate
10. 10
    여과filtered
11. 11
    기타evaporated
12. 12
    기타to give a solid
13. 13
    세척eluted through a silica column (5 g) with methyl isobutyl ketone:acetic acid:water 2:1:1
14. 14
    농축concentrated in vacuo
15. 15
    기타to give a film
16. 16
    건조diethyl ether and dried in vacuo

실험 절차

4-[2-(1-azetidin-3-yl-1H-pyrazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide (Example 801, 54 mg, 0.1 mmol) was stirred with dichloromethane (2 mL) methanol (0.2 mL) and 37% w/v aqueous formaldehyde solution (0.025 mL, 0.34 mmol) at room temperature for 15 minutes. Sodium triacetoxyborohydride (68 mg, 0.32 mmol) was added at the reaction stirred at room temperature for 18 hours. 37% wt/vol aqueous formaldehyde solution (0.025 mL, 0.34 mmol) was added and the reaction stirred for 15 minutes then sodium triacetoxyborohydride (68 mg, 0.32 mmol) was added at the reaction stirred at room temperature for 3 hours. The mixture was evaporated and the residue dissolved in ethyl acetate (20 mL) and washed with saturated aqueous sodium bicarbonate solution (2×10 ml) and saturated aqueous sodium chloride solution (2×10 ml). The organic layer was separated, dried over sodium sulphate, filtered and evaporated to give a solid. The solid was suspended in methyl isobutyl ketone:acetic acid:water 2:1:1 and eluted through a silica column (5 g) with methyl isobutyl ketone:acetic acid:water 2:1:1. The appropriate fractions were combined and concentrated in vacuo to give a film. This was scratched with ethyl acetate then diethyl ether and dried in vacuo to give the title compound as a white solid. Yield 30 mg. 54%.

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