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HCID 72548394, 화합물 → (S)-2-[2-(4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoyloxy)-acetylamino]-pentanedioic acid

HRID 2206434
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HRID 2206434 반응식
C([O:8][C:9](=[O:69])[C@@H:10]([NH:23][C:24](=[O:68])[CH2:25][O:26][C:27](=[O:67])[C:28]1[CH:33]=[CH:32][C:31]([NH:34][C:35]([C@H:37]2[C@H:41]([C:42]3[CH:47]=[CH:46][CH:45]=[C:44]([Cl:48])[C:43]=3[F:49])[C@:40]([C:52]3[CH:57]=[CH:56][C:55]([Cl:58])=[CH:54][C:53]=3[F:59])([C:50]#[N:51])[C@H:39]([CH2:60][C:61]([CH3:64])([CH3:63])[CH3:62])[NH:38]2)=[O:36])=[C:30]([O:65][CH3:66])[CH:29]=1)[CH2:11][CH2:12][C:13]([O:15]CC1C=CC=CC=1)=[O:14])C1C=CC=CC=1>[Pd].C(O)(C)C>[Cl:58][C:55]1[CH:56]=[CH:57][C:52]([C@@:40]2([C:50]#[N:51])[C@H:39]([CH2:60][C:61]([CH3:62])([CH3:64])[CH3:63])[NH:38][C@@H:37]([C:35]([NH:34][C:31]3[CH:32]=[CH:33][C:28]([C:27]([O:26][CH2:25][C:24]([NH:23][C@@H:10]([CH2:11][CH2:12][C:13]([OH:15])=[O:14])[C:9]([OH:69])=[O:8])=[O:68])=[O:67])=[CH:29][C:30]=3[O:65][CH3:66])=[O:36])[C@@H:41]2[C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([Cl:48])[C:43]=2[F:49])=[C:53]([F:59])[CH:54]=1
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참가 물질

4

반응물 1

HCID 72548394HCID 72548394, 화합물

생성물 1

HCID 86704085(S)-2-[2-(4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoyloxy)-acetylamino]-pentanedioic acid

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 3776Isopropanol용매

실험 절차

In a 25 mL three-necked flask, (S)-dibenzyl 2-(2-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoyloxy)acetamido)pentanedioate (Example 70, 61 mg, 62.0 μmol) was combined with isopropanol (5 mL) at room temperature. Then palladium on carbon (33.0 mg, 31.0 μmol) was added. The flask was flushed with nitrogen, and then replaced with hydrogen. It was stirred at room temperature under hydrogen balloon. After 30 min, the reaction mix was filtered through a Celite cake to remove the catalyst. The Celite cake was washed thoroughly with isopropanol. The filtrate and washing solutions were combined and concentrated to give a crude product, which was purified with reverse phase high-performance liquid chromatography. The pure fractions were concentrated and lyophilized to give (S)-2-[2-(4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoyloxy)-acetylamino]-pentanedioic acid as a white product (20 mg, 33% yield). LCMS (ES+) m/z calcd. for C38H39Cl2F2N4O9 [(M+H)+]: 803. found: 803.

후처리

  1. customThe flask was flushed with nitrogen
  2. additionthe reaction mix
  3. filtrationwas filtered through a Celite cake
  4. customto remove the catalyst
  5. washThe Celite cake was washed thoroughly with isopropanol
  6. washThe filtrate and washing solutions
  7. concentrationconcentrated
  8. customto give a crude product, which
  9. customwas purified with reverse phase high-performance liquid chromatography
  10. concentrationThe pure fractions were concentrated

출처 및 근거

ORD 기록
ord-0407842751eb4909b8e950f862114025
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09371280B2

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