Hydrogen Peroxide → 2-Oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-phenyl)-amide

HRID 417261노트

반응식

HRID 417261 반응식
Cl[C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:43])[C@:10]3([C@@H:14](C4C=CC=C(Cl)C=4F)[C@H:13]([C:23](=[O:33])[NH:24][C:25]4[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][CH:26]=4)[NH:12][C@H:11]3CC(C)(C)COC(=O)C)[C:5]2=[CH:4][CH:3]=1.[OH:44]O.[OH-].[Na+]>CS(C)=O>[C:31]([C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:23]([CH:13]2[NH:12][CH2:11][C:10]3([C:5]4[C:6](=[CH:7][CH:2]=[CH:3][CH:4]=4)[NH:8][C:9]3=[O:43])[CH2:14]2)=[O:33])=[CH:26][CH:27]=1)(=[O:44])[NH2:32]

참가 물질

5

반응물 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 53239123acetic acid rac-3-[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-5'-(4-cyano-phenylcarbamoyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidin]-2'-yl]-2,2-dimethyl-propyl ester

생성물 1

HCID 1236048552-Oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-phenyl)-amide수율 160.3%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

실험 절차

To the solution of acetic acid rac-3-[(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-5′-(4-cyano-phenylcarbamoyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidin]-2′-yl]-2,2-dimethyl-propyl ester prepared in Example 104 (80 mg, 0.13 mmol) in DMSO (0.5 mL) at 0° C. was added an aqueous solution (30% Aldrich) of H2O2 (0.22 g, 1.9 mmol), then aqueous solution (1N) of NaOH (0.64 mL, 0.64 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 5 h. The mixture was partitioned between ethyl acetate and saturated aqueous Na2SO3 solution. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (50 to 100% EtOAc in CH2Cl2) to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′43-hydroxy-2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-carbamoyl-phenyl)-amide as a white solid (Yield 73 mg, 95%)

후처리

  1. customThe mixture was partitioned between ethyl acetate and saturated aqueous Na2SO3 solution
  2. customThe organic layer was separated
  3. washwashed with water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (50 to 100% EtOAc in CH2Cl2)

출처 및 근거

ORD 기록
ord-f7747d3f5947432aab5ef575c385aceb
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08088815B2

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