5-Isocyanato-1,3-dioxaindane → N-({1-[4-(3-Benzo[1,3]dioxol-5-yl-ureido)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

HRID 2188584노트

반응식

HRID 2188584 반응식
[N:1]([C:4]1[CH:12]=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)=[C:2]=[O:3].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>CN(C=O)C>[O:8]1[C:7]2[CH:11]=[CH:12][C:4]([NH:1][C:2](=[O:3])[NH:20][CH:21]3[CH2:22][CH2:23][CH:24]([N:27]4[CH2:30][CH:29]([NH:31][C:32]([CH2:34][NH:35][C:36](=[O:47])[C:37]5[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:44])([F:45])[F:46])[CH:38]=5)=[O:33])[CH2:28]4)[CH2:25][CH2:26]3)=[CH:5][C:6]=2[O:10][CH2:9]1

참가 물질

4

반응물 2

HCID 52232135-Isocyanato-1,3-dioxaindaneHCID 86646662N-{[1-(4-Amino-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide TFA salt

생성물 1

HCID 49763338N-({1-[4-(3-Benzo[1,3]dioxol-5-yl-ureido)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

5-Isocyanato-benzo[1,3]dioxole (Aldrich, 50 mg, 0.302 mmol) was added into a solution of N-{[1-(4-amino-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide TFA salt (150 mg, 0.302 mmol) and TEA (127 μL, 0.906 mmol) in DMF (3 mL) at room temperature. The reaction was stirred overnight 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 layers were 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 layers were 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-c420370e899d4d12ac1be46e9aea3e48
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08324186B2

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