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

反応式

HRID 1171964 の反応式
[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

参加物

6

反応物 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

生成物 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-carboxylate収率 84%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

(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.

後処理

  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)

出典と根拠

ORDレコード
ord-81cb13ee9041467ca41ed5aff498425c
出典データセット
uspto-grants-2010_11
特許番号
US07829665B2

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