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 (2,2-dimethylpropyl)amide hemifumarate

HRID 1694948노트

반응식

HRID 1694948 반응식
FC(F)(F)C(O)=O.C(OC(=O)[NH:14][C@@H:15]([CH2:31][N:32]1[CH2:37][C:36](=[O:38])[N:35]([C:39]2[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=2[CH3:46])[CH2:34][C:33]1([CH3:48])[CH3:47])[C@@H:16]([OH:30])[CH2:17][C@H:18]([C:22](=[O:29])[NH:23][CH2:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH:19]([CH3:21])[CH3:20])(C)(C)C.[C:50]([OH:57])(=[O:56])/[CH:51]=[CH:52]/[C:53]([OH:55])=[O:54].[CH3:58][C:59]([CH3:92])([CH3:91])[CH2:60][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]>C(Cl)Cl.CO>[C:50]([OH:57])(=[O:56])/[CH:51]=[CH:52]/[C:53]([OH:55])=[O:54].[CH3:28][C:25]([CH3:26])([CH3:27])[CH2:24][NH:23][C:22](=[O:29])[C@H:18]([CH:19]([CH3:20])[CH3:21])[CH2:17][C@H:16]([OH:30])[C@@H:15]([NH2:14])[CH2:31][N:32]1[CH2:37][C:36](=[O:38])[N:35]([C:39]2[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=2[CH3:46])[CH2:34][C:33]1([CH3:47])[CH3:48].[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([CH3:83])[CH3:84])[C@@H:65]([OH:86])[CH2:64][C@@H:63]([CH:87]([CH3:88])[CH3:89])[C:62]([NH:61][CH2:60][C:59]([CH3:92])([CH3:91])[CH3:58])=[O:90]

참가 물질

7

반응물 4

HCID 6422Trifluoroacetic acidHCID 444972Fumaric AcidHCID 24966888(2s,4s,5s)-5-Amino-6-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid (2,2-dimethylpropyl)amideHCID 66645581{(1S,2S,4S)-4-(2,2-Dimethylpropylcarbamoyl)-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 131729637(2S,4S,5S)-5-Amino-6-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid (2,2-dimethylpropyl)amide hemifumarate수율 75.7%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

0.69 ml of trifluoroacetic acid (8.96 mmol) was added to a solution of 177 mg of {(1S,2S,4S)-4-(2,2-dimethylpropylcarbamoyl)-1-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester obtained in Example (70g) (0.30 mmol) in methylene chloride (1.4 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/triethylamine=100/10/1). 14 mg of fumaric acid (0.12 mmol) was added to a solution of 122 mg of the resulting (2S,4S,5S)-5-amino-6-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid (2,2-dimethylpropyl)amide (0.25 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 100 mg of the title compound (yield: 74%).

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/triethylamine=100/10/1)
  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-e6eafca11eb041ee92ab4094c1f3c185
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08158790B2

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