반응 #2275765

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Benzo[1,3]dioxole-5-carbonyl chloride

N-{[1-(4-amino-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide TFA salt

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title compound

Benzo[1,3]dioxole-5-carboxylic acid (4-{3-[2-(3-trifluoromethyl-benzoylamino)-acetylamino]-azetidin-1-yl}-cyclohexyl)-amide

용매

DCM

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후처리

1. 1
   기타quenched with saturated sodium bicarbonate
2. 2
   기타The reaction was then partitioned between DCM and water
3. 3
   기타The organic layer was separated
4. 4
   추출the aqueous layer was extracted 3 times with a chloroform/IPA “cocktail” (˜3:1
5. 5
   건조The combined organic layer was dried over anhydrous Na2SO4
6. 6
   여과filtered
7. 7
   농축concentrated
8. 8
   기타to give the crude product, which
9. 9
   기타was then purified by a CombiFlash® system

실험 절차

Benzo[1,3]dioxole-5-carbonyl chloride (Aldrich, 74 mg, 0.404 mmol) was added into a solution of N-{[1-(4-amino-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide TFA salt (as prepared in the previous step 200 mg, 0.404 mmol) and TEA (170 μL, 1.21 mmol) in DCM (5 mL) at 0° C. The reaction was stirred for an additional 2 hours and quenched with saturated sodium bicarbonate. The reaction was then partitioned between DCM and water. The organic layer was separated and the aqueous layer was extracted 3 times with a chloroform/IPA “cocktail” (˜3:1, v/v). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was then purified by a CombiFlash® system using ethyl acetate and 7N NH3 in MeOH as eluent (from pure ethyl acetate to 5% 7N NH3 in MeOH in ethyl acetate) to afford the title compound as white solid.

출처