Trifluoroacetic acid → (2S,4S,5S)-5-Amino-6-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid isobutylamide hemifumarate

HRID 1694950노트

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HRID 1694950 반응식
FC(F)(F)C(O)=O.C(OC(=O)[NH:14][C@@H:15]([CH2:30][N:31]1[CH2:36][C:35](=[O:37])[N:34]([C:38]2[CH:43]=[C:42]([F:44])[CH:41]=[CH:40][C:39]=2[CH3:45])[CH2:33][C:32]1([CH3:47])[CH3:46])[C@@H:16]([OH:29])[CH2:17][C@H:18]([C:22](=[O:28])[NH:23][CH2:24][CH:25]([CH3:27])[CH3:26])[CH:19]([CH3:21])[CH3:20])(C)(C)C.[C:49]([OH:56])(=[O:55])/[CH:50]=[CH:51]/[C:52]([OH:54])=[O:53].[CH2:57]([NH:61][C:62](=[O:90])[C@H:63]([CH:87]([CH3:89])[CH3:88])[CH2:64][C@H:65]([OH:86])[C@@H:66]([NH2:85])[CH2:67][N:68]1[CH2:73][C:72](=[O:74])[N:71]([C:75]2[CH:80]=[C:79]([F:81])[CH:78]=[CH:77][C:76]=2[CH3:82])[CH2:70][C:69]1([CH3:84])[CH3:83])[CH:58]([CH3:60])[CH3:59]>C(Cl)Cl.CO>[C:49]([OH:56])(=[O:55])/[CH:50]=[CH:51]/[C:52]([OH:54])=[O:53].[CH2:24]([NH:23][C:22](=[O:28])[C@H:18]([CH:19]([CH3:21])[CH3:20])[CH2:17][C@H:16]([OH:29])[C@@H:15]([NH2:14])[CH2:30][N:31]1[CH2:36][C:35](=[O:37])[N:34]([C:38]2[CH:43]=[C:42]([F:44])[CH:41]=[CH:40][C:39]=2[CH3:45])[CH2:33][C:32]1([CH3:46])[CH3:47])[CH:25]([CH3:27])[CH3:26].[NH2:85][C@@H:66]([CH2:67][N:68]1[CH2:73][C:72](=[O:74])[N:71]([C:75]2[CH:80]=[C:79]([F:81])[CH:78]=[CH:77][C:76]=2[CH3:82])[CH2:70][C:69]1([CH3:84])[CH3:83])[C@@H:65]([OH:86])[CH2:64][C@@H:63]([CH:87]([CH3:88])[CH3:89])[C:62]([NH:61][CH2:57][CH:58]([CH3:60])[CH3:59])=[O:90]

참가 물질

7

반응물 4

HCID 6422Trifluoroacetic acidHCID 444972Fumaric AcidHCID 24966887(2s,4s,5s)-5-Amino-6-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid isobutylamideHCID 66645880{(1S,2S,4S)-4-Isobutylcarbamoyl-1-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester

생성물 1

HCID 131729638(2S,4S,5S)-5-Amino-6-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid isobutylamide hemifumarate수율 80%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

0.95 ml of trifluoroacetic acid (12.33 mmol) was added to a solution of 238 mg of {(1S,2S,4S)-4-isobutylcarbamoyl-1-[4-(5-fluoro-2-methylphenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester obtained in Example (71a) (0.411 mmol) in methylene chloride (2 ml) at room temperature, and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure and diluted with a saturated sodium bicarbonate aqueous solution, followed by extraction with methylene chloride. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent: methylene chloride/methanol=20/1-10/1). 20.8 mg of fumaric acid (0.179 mmol) was added to a solution of 172 mg of (2S,4S,5S)-5-amino-6-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid isobutylamide obtained above (0.35 mmol) in methanol (2 ml), and the mixture was stirred at room temperature for five minutes. The solvent was evaporated under reduced pressure to obtain 152 mg of the title compound (yield: 80%).

후처리

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with a saturated sodium bicarbonate aqueous solution
  3. extractionfollowed by extraction with methylene chloride
  4. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
  5. filtrationAfter filtration
  6. customthe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (elution solvent: methylene chloride/methanol=20/1-10/1)
  8. stirringthe mixture was stirred at room temperature for five minutes
  9. customThe solvent was evaporated under reduced pressure

출처 및 근거

ORD 기록
ord-d2b0275f4e09475bb6e6836256d9b357
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08158790B2

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