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Toluene → (2S,4S)-benzyl 2-(5-(4'-(2-((2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methylthio)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate

HRID 1751652
ノート
印刷プレビュー

反応式

HRID 1751652 の反応式
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:57]([CH3:59])[CH3:58])[C:7]([N:9]1[CH2:13][C@@H:12]([S:14][CH3:15])[CH2:11][C@H:10]1[C:16]([NH:18][CH2:19][C:20]([C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][C:31]([C:34]3[NH:38][C:37]([C@@H:39]4[CH2:43][C@H:42]([CH2:44][O:45][CH3:46])[CH2:41][N:40]4C(OCC4C=CC=CC=4)=O)=[N:36][CH:35]=3)=[CH:30][CH:29]=2)=[CH:24][CH:23]=1)=O)=O)=[O:8])=[O:4].[C:60]1(C)C=[CH:64][CH:63]=[CH:62][CH:61]=1.C([O-])(=O)C.[NH4+:71].[CH3:72][CH2:73][O:74][C:75](C)=[O:76]>>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:57]([CH3:59])[CH3:58])[C:7]([N:9]1[CH2:13][C@@H:12]([S:14][CH3:15])[CH2:11][C@H:10]1[C:16]1[NH:71][C:20]([C:22]2[CH:23]=[CH:24][C:25]([C:28]3[CH:29]=[CH:30][C:31]([C:34]4[NH:38][C:37]([C@@H:39]5[CH2:43][C@H:42]([CH2:44][O:45][CH3:46])[CH2:41][N:40]5[C:75]([O:74][CH2:73][C:72]5[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=5)=[O:76])=[N:36][CH:35]=4)=[CH:32][CH:33]=3)=[CH:26][CH:27]=2)=[CH:19][N:18]=1)=[O:8])=[O:4]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 4

HCID 1140TolueneHCID 8857Ethyl AcetateHCID 517165Ammonium AcetateHCID 67682446(2S,4S)-benzyl 2-(5-(4'-(2-((2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methylthio)pyrrolidine-2-carboxamido)acetyl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate

生成物 1

HCID 86708800
(2S,4S)-benzyl 2-(5-(4'-(2-((2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methylthio)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate
収率 58%

反応条件

温度
110 °C

実験手順

To (2S,4S)-benzyl 2-(5-(4′-(2-((2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methylthio)pyrrolidine-2-carboxamido)acetyl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (487 mg, 0.59 mmol) was added PhMe (6 mL), MeOEtOH (1 mL), and ammonium acetate (0.91 g, 11.8 mmol) and the solution was heated to 110° C. The solution was stirred for 3 h and then cooled to rt and was diluted with EtOAc and washed successively with water, saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc) to afford (2S,4S)-benzyl 2-(5-(4′-(2-((2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methylthio)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (276 mg, 58%).

後処理

  1. temperaturecooled to rt
  2. washwashed successively with water, saturated aqueous NaHCO3 and brine
  3. dry with materialThe organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc)

出典と根拠

ORDレコード
ord-ad0eeb52b5914788954c7d7278698658
出典データセット
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09156823B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート