HCID 72548394, compound → (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 2206434Notes

Reaction equation

HRID 2206434 reaction equation
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

Participants

4

Reactant 1

HCID 72548394HCID 72548394, compound

Product 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

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 3776IsopropanolSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-0407842751eb4909b8e950f862114025
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

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