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

반응식

HRID 227949 반응식
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

참가 물질

6

반응물 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

생성물 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-carbonitrile수율 78.4%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-0b0f2c9c65124fed9eab8aa98b339649
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07560569B2

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