Triethylamine → rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-butoxy-4-carbamoyl-phenyl)-amide

HRID 417307Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 417307
[CH2:1]([O:5][C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][C:14]=1[NH:15][C:16]([C@@H:18]1[NH:22][C@@H:21]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C@:20]2([C:35]3[C:30](=[CH:31][C:32]([Cl:36])=[CH:33][CH:34]=3)[NH:29][C:28]2=[O:37])[C@H:19]1[C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[C:39]=1[F:45])=[O:17])[C:9]([OH:11])=O)[CH2:2][CH2:3][CH3:4].CC[N:48]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH4+].[Cl-].C(N(CC)CC)C>CN(C=O)C>[CH2:1]([O:5][C:6]1[CH:7]=[C:8]([C:9](=[O:11])[NH2:48])[CH:12]=[CH:13][C:14]=1[NH:15][C:16]([CH:18]1[NH:22][CH:21]([CH2:23][C:24]([CH3:25])([CH3:27])[CH3:26])[C:20]2([C:35]3[C:30](=[CH:31][C:32]([Cl:36])=[CH:33][CH:34]=3)[NH:29][C:28]2=[O:37])[CH:19]1[C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[C:39]=1[F:45])=[O:17])[CH2:2][CH2:3][CH3:4]

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 53237755rac-3-butoxy-4-{[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carbonyl]amino}-benzoic acid

Produkt 1

HCID 75985950rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-butoxy-4-carbamoyl-phenyl)-amideAusbeute 89,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of rac-3-butoxy-4-{[(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carbonyl]-amino}-benzoic acid (0.1 g, 0.15 mmol) prepared in Example 151 in anhydrous DMF (2 mL) were added EDCI (59 mg, 0.31 mmol), HOBt (41 mg, 0.31 mmol), NH4Cl (81 mg, 1.5 mmol), and triethylamine (31 mg, 0.31 mmol) sequentially. The reaction mixture was heated at 80° C. for 1 h. The mixture was cooled to room temperature, then partitioned between ethyl acetate and water. The organic layer was separated, and aqueous layer was extracted with ethyl acetate twice. The combined organic extract was washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (25-100% EtOAc in hexanes) to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (2-butoxy-4-carbamoyl-phenyl)-amide as a white solid (88 mg, 89%).

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. extractionaqueous layer was extracted with ethyl acetate twice
  5. extractionThe combined organic extract
  6. washwas washed with water, brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography (25-100% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-962a6f86669a45f1acfa53be683d063d
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08088815B2

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