Triethylamine → (2S,4S)-1-[[N-benzyloxycarbonyl-[4-(4-fluoropiperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

HRID 227949

反応式

HRID 227949 の反応式
Cl.[F:2][CH:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.C(N(CC)CC)C.[CH2:16]([O:23][C:24]([N:26]([CH2:47][C:48]([N:50]1[CH2:54][C@@H:53]([F:55])[CH2:52][C@H:51]1[C:56]#[N:57])=[O:49])[C:27]12[CH2:34][CH2:33][C:30]([C:35](ON3C4C=CC=CC=4N=N3)=[O:36])([CH2:31][CH2:32]1)[CH2:29][CH2:28]2)=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>O1CCCC1.ClCCl>[CH2:16]([O:23][C:24]([N:26]([CH2:47][C:48]([N:50]1[CH2:54][C@@H:53]([F:55])[CH2:52][C@H:51]1[C:56]#[N:57])=[O:49])[C:27]12[CH2:34][CH2:33][C:30]([C:35]([N:6]3[CH2:7][CH2:8][CH:3]([F:2])[CH2:4][CH2:5]3)=[O:36])([CH2:31][CH2:32]1)[CH2:29][CH2:28]2)=[O:25])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

参加物

6

反応物 3

HCID 8471TriethylamineHCID 27591584-Fluoropiperidine hydrochlorideHCID 57756828(2S,4S)-1-[(N-benzyloxycarbonyl-N-[4-(benzotriazol-1-yl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

生成物 1

HCID 68843336(2S,4S)-1-[[N-benzyloxycarbonyl-[4-(4-fluoropiperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile収率 78.4%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

4-Fluoropiperidine hydrochloride (18.2 mg) was suspended in tetrahydrofuran (0.87 mL). While this suspension was chilled in an ice bath, triethylamine (18.2 μL) was added and the mixture was stirred at the same temperature for 35 minutes. Subsequently, (2S,4S)-1-[[N-benzyloxycarbonyl-N-[4-(benzotriazol-1-yl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (50.0 mg) was added and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and washed sequentially with 0.1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine. The organic layer was dried over anhydrous sodium sulfate and was concentrated under reduced pressure. The resulting residue was purified by column chromatography (eluant:ethyl acetate:methanol=20:1) to give (2S,4S)-1-[[N-benzyloxycarbonyl-[4-(4-fluoropiperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (37.0 mg).

後処理

  1. temperatureWhile this suspension was chilled in an ice bath
  2. stirringthe mixture was stirred at room temperature overnight
  3. washwashed sequentially with 0.1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationwas concentrated under reduced pressure
  6. customThe resulting residue was purified by column chromatography (eluant:ethyl acetate:methanol=20:1)

出典と根拠

ORDレコード
ord-0b0f2c9c65124fed9eab8aa98b339649
出典データセット
uspto-grants-2009_07
特許番号
US07560569B2

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