Water → 2-((2-benzyloxycarbonylamino-3-(4-fluorophenyl)propionyl)-N-methylamino)-3-methylbutyric acid 2-(3-t-butyl-4-hydroxyphenyl)-1-methanesulfonylmethylethylamide

HRID 1988257노트

반응식

HRID 1988257 반응식
[C:1]([C:5]1[CH:6]=[C:7]([CH2:12][CH:13]([NH:19][C:20](=[O:37])[CH:21]([NH:25][CH2:26]C(OCC2C=CC=CC=2)=O)[CH:22]([CH3:24])[CH3:23])[CH2:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:8]=[CH:9][C:10]=1[OH:11])([CH3:4])([CH3:3])[CH3:2].[H][H].[NH:40]([C:53]([O:55][CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)=[O:54])[C@H:41]([C:50]([OH:52])=O)[CH2:42][C:43]1[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=1.O>CO.C1COCC1.[C].[Pd]>[C:1]([C:5]1[CH:6]=[C:7]([CH2:12][CH:13]([NH:19][C:20](=[O:37])[CH:21]([N:25]([C:50](=[O:52])[CH:41]([NH:40][C:53]([O:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)=[O:54])[CH2:42][C:43]2[CH:44]=[CH:45][C:46]([F:49])=[CH:47][CH:48]=2)[CH3:26])[CH:22]([CH3:23])[CH3:24])[CH2:14][S:15]([CH3:18])(=[O:16])=[O:17])[CH:8]=[CH:9][C:10]=1[OH:11])([CH3:2])([CH3:4])[CH3:3]

참가 물질

8

반응물 4

HCID 962WaterHCID 7020267(S)-2-(((Benzyloxy)carbonyl)amino)-3-(4-fluorophenyl)propanoic acidHCID 876061162-(Benzyloxycarbonyl)methylamino-3-methylbutyric acid 2-(3-t-butyl-4-hydroxyphenyl)-1-methanesulfonylmethylethylamideHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 876058792-((2-benzyloxycarbonylamino-3-(4-fluorophenyl)propionyl)-N-methylamino)-3-methylbutyric acid 2-(3-t-butyl-4-hydroxyphenyl)-1-methanesulfonylmethylethylamide수율 57%

시약·촉매·용매 3

HCID 178418390HCID 178418390, 화합물촉매HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 2-(benzyloxycarbonyl)methylamino-3-methylbutyric acid 2-(3-t-butyl-4-hydroxyphenyl)-1-methanesulfonylmethylethylamide (0.65 g, 1.22 mmol) in methanol (10 ml), 10% palladium carbon (130 mg) was added and stirred in a hydrogen atmosphere at room temperature for 30 min. After filtration, the filtrate was concentrated under reduced pressure. To a solution of the thus obtained residue, Z-Phe(4-F)-OH (465 mg, 1.47 mmol) and CMPI (375 mg, 1.47 mmol) in THF (15 ml), TEA (0.41 ml, 2.93 mmol) was added under cooling with ice and stirred at room temperature overnight. The reaction mixture was mixed with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated to remove the solvent under reduced pressure; the thus obtained residue was subjected to silica gel column chromatography (developing solvent:n-hexane:ethyl acetate=1:1) to give 2-((2-benzyloxycarbonylamino-3-(4-fluorophenyl)propionyl)-N-methylamino)-3-methylbutyric acid 2-(3-t-butyl-4-hydroxyphenyl)-1-methanesulfonylmethylethylamide (484 mg, 57%). A mixture of the above compound (424 mg, 0.609 mmol) and 10% palladium carbon (43 mg) in methanol (16 ml) was stirred at room temperature in a hydrogen atmosphere for 2 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure; the thus obtained residue was subjected to silica gel column chromatography (developing solvent: methylene chloride:methanol=15:1), giving the titled compound (239 mg, 70%).

후처리

  1. filtrationAfter filtration
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. temperatureunder cooling with ice
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated
  8. customto remove the solvent under reduced pressure

출처 및 근거

ORD 기록
ord-cb2ea9d146994c48bb181b0470aecbbb
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07553969B1

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