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

HRID 2188583

반응식

HRID 2188583 반응식
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10](Cl)=[O:11])=[CH:9][C:4]=2[O:3][CH2:2]1.OC(C(F)(F)F)=O.[NH2:20][CH:21]1[CH2:26][CH2:25][CH:24]([N:27]2[CH2:30][CH:29]([NH:31][C:32]([CH2:34][NH:35][C:36](=[O:47])[C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[CH:38]=3)=[O:33])[CH2:28]2)[CH2:23][CH2:22]1>C(Cl)Cl>[F:46][C:43]([F:44])([F:45])[C:39]1[CH:38]=[C:37]([CH:42]=[CH:41][CH:40]=1)[C:36]([NH:35][CH2:34][C:32]([NH:31][CH:29]1[CH2:28][N:27]([CH:24]2[CH2:23][CH2:22][CH:21]([NH:20][C:10]([C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)=[O:11])[CH2:26][CH2:25]2)[CH2:30]1)=[O:33])=[O:47]

참가 물질

4

반응물 2

HCID 27347491,3-Benzodioxole-5-carbonyl chlorideHCID 86646662N-{[1-(4-Amino-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide TFA salt

생성물 1

HCID 49763337Benzo[1,3]dioxole-5-carboxylic acid (4-{3-[2-(3-trifluoromethyl-benzoylamino)-acetylamino]-azetidin-1-yl}-cyclohexyl)-amide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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.

후처리

  1. customquenched with saturated sodium bicarbonate
  2. customThe reaction was then partitioned between DCM and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted 3 times with a chloroform/IPA “cocktail” (˜3:1
  5. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas then purified by a CombiFlash® system

출처 및 근거

ORD 기록
ord-96d423cb081e4ff3b151feca3af765ac
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08324186B2

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