Potassium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(4-(1-methyl-2-oxoindolin-6-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216950

반응식

HRID 216950 반응식
[NH2:1][C:2](=[O:37])[C@@H:3]([NH:20][C:21]([C:23]1([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH:6]=1.Br[C:39]1[CH:47]=[C:46]2[C:42]([CH2:43][C:44](=[O:49])[N:45]2[CH3:48])=[CH:41][CH:40]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[NH2:1][C:2](=[O:37])[C@@H:3]([NH:20][C:21]([C:23]1([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:39]2[CH:47]=[C:46]3[C:42]([CH2:43][C:44](=[O:49])[N:45]3[CH3:48])=[CH:41][CH:40]=2)=[CH:7][CH:6]=1

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 580060486-Bromo-1-methylindolin-2-oneHCID 59568592(S)-tert-Butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

생성물 1

HCID 59568615(S)-tert-Butyl 4-(1-amino-3-(4-(1-methyl-2-oxoindolin-6-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate수율 21.8%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

A solution of (S)-tert-butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 16, step (i), 200 mg) and 6-bromo-1-methylindolin-2-one (87 mg) in acetonitrile (5 mL) was treated with potassium carbonate (107 mg) and purged with nitrogen. 1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (15 mg) was added and the reaction stirred is under reflux under nitrogen for 4 h and then evaporated in vacuo. The residue was partitioned between water (40 mL) and ethyl acetate (40 mL). The aqueous was further extracted with ethyl acetate (40 mL) and the combined organic extracts were dried over magnesium sulfate and evaporated in vacuo. The crude product was purified by flash silica chromatography eluting with ethyl acetate. Pure fractions were evaporated to dryness to afford the sub-titled compound (45 mg).

후처리

  1. custompurged with nitrogen
  2. addition1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (15 mg) was added
  3. temperatureunder reflux under nitrogen for 4 h
  4. customevaporated in vacuo
  5. customThe residue was partitioned between water (40 mL) and ethyl acetate (40 mL)
  6. extractionThe aqueous was further extracted with ethyl acetate (40 mL)
  7. dry with materialthe combined organic extracts were dried over magnesium sulfate
  8. customevaporated in vacuo
  9. customThe crude product was purified by flash silica chromatography
  10. washeluting with ethyl acetate
  11. customPure fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-280a24705fce4a63a39b00de3ffbce0a
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193239B2

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