1,1'-Carbonyldiimidazole → (3R,5S)-1-((S)-4-(N-(but-3-enyl)-2-nitrophenylsulfonamido)-2-(tert-butoxycarbonylamino) butanoyl)-5-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylate

HRID 1171964

Reaktionsgleichung

Reaktionsgleichung von HRID 1171964
[CH2:1]([N:5]([CH2:18][CH2:19][C@H:20]([NH:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[C:21]([N:23]1[CH2:27][C@H:26]([OH:28])[CH2:25][C@H:24]1[C:29]([NH:31][C@:32]1([C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:34][C@H:33]1[CH:35]=[CH2:36])=[O:30])=[O:22])[S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16])(=[O:8])=[O:7])[CH2:2][CH:3]=[CH2:4].N1([C:55]([N:57]2[CH:61]=[CH:60]N=[CH:58]2)=[O:56])C=CN=C1.C(N(C(C)C)C(C)C)C.Cl.[F:72][C:73]1C=[CH:80][CH:79]=[C:78]2[C:74]=1CNC2>C1(C)C=CC=CC=1>[F:72][C:73]1[CH:74]=[CH:78][CH:79]=[C:80]2[C:60]=1[CH2:61][N:57]([C:55]([O:28][C@@H:26]1[CH2:25][C@@H:24]([C:29](=[O:30])[NH:31][C@:32]3([C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:34][C@H:33]3[CH:35]=[CH2:36])[N:23]([C:21](=[O:22])[C@@H:20]([NH:42][C:43]([O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[O:44])[CH2:19][CH2:18][N:5]([CH2:1][CH2:2][CH:3]=[CH2:4])[S:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N+:15]([O-:17])=[O:16])(=[O:8])=[O:7])[CH2:27]1)=[O:56])[CH2:58]2

Komponenten

6

Edukt 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 426096434-Fluoro-1H-isoindoline hydrochlorideHCID 59554237(1R,2S)-ethyl 1-((2S,4R)-1-((S)-4-(N-(but-3-enyl)-2-nitrophenylsulfonamido)-2-(tert-butoxycarbonylamino)butanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate

Produkt 1

HCID 59554077(3R,5S)-1-((S)-4-(N-(but-3-enyl)-2-nitrophenylsulfonamido)-2-(tert-butoxycarbonylamino) butanoyl)-5-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylateAusbeute 84 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Versuchsvorschrift

(1R,2S)-ethyl 1-((2S,4R)-1-((S)-4-(N-(but-3-enyl)-2-nitrophenylsulfonamido)-2-(tert-butoxycarbonylamino)butanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate (1.60 g, 2.26 mmol) in toluene (20 mL) was added di(1H-imidazol-1-yl)methanone (0.48 g, 2.94 mmol) in one portion. The reaction was stirred at rt for 3 hrs. To the reaction was then added the N-ethyl-N-isopropylpropan-2-amine (1.97 ml, 11.30 mmol), followed by 4-Fluoroisoindoline hydrochloride (1.27 g, 4.52 mmol). The reaction was stirred at 60° C. for 3 hrs. The solvent was removed. The residue was partitioned between ethyl acetate (30 mL) and saturated sodium bicarbonate solution. The organic layer was separated and dried over sodium sulfate. After removal of solvent, the residue was purified by chromatography (Hexane:Ethyl acetate=1:2) to give (3R,5S)-1-((S)-4-(N-(but-3-enyl)-2-nitrophenylsulfonamido)-2-(tert-butoxycarbonylamino)butanoyl)-5-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylate as white solid (1.65 g, 84%). MS: Calcd.: 870; Found: [M+H]+ 871.

Aufarbeitung

  1. stirringThe reaction was stirred at 60° C. for 3 hrs
  2. customThe solvent was removed
  3. customThe residue was partitioned between ethyl acetate (30 mL) and saturated sodium bicarbonate solution
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. customAfter removal of solvent
  7. customthe residue was purified by chromatography (Hexane:Ethyl acetate=1:2)

Quellen und Nachweise

ORD-Eintrag
ord-81cb13ee9041467ca41ed5aff498425c
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07829665B2

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