Water → Bisegliptin

HRID 555679

반응식

HRID 555679 반응식
[NH2:1][C:2]12[CH2:9][CH2:8][C:5]([C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.C(NC(C)C)(C)C.Br[CH2:23][C:24]([N:26]1[CH2:30][C@@H:29]([F:31])[CH2:28][C@H:27]1[C:32]#[N:33])=[O:25].O>C(#N)C>[CH2:13]([O:12][C:10]([C:5]12[CH2:4][CH2:3][C:2]([NH:1][CH2:23][C:24]([N:26]3[CH2:30][C@@H:29]([F:31])[CH2:28][C@H:27]3[C:32]#[N:33])=[O:25])([CH2:9][CH2:8]1)[CH2:7][CH2:6]2)=[O:11])[CH3:14]

참가 물질

6

반응물 4

HCID 962WaterHCID 7912DiisopropylamineHCID 21090395(2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrileHCID 23149693Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate

생성물 1

HCID 11688894Bisegliptin수율 88.3%

시약·촉매·용매 1

HCID 6342Acetonitrile용매2회

실험 절차

Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (92.0 mg) was dissolved in acetonitrile (2 mL) and diisopropylamine (100 μL) was added to the solution. While the mixture was chilled in an ice bath, (2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile (100 mg) in acetonitrile (1 mL) was added dropwise. The mixture was stirred for 1.5 hours while chilled in the ice bath. Subsequently, water was added and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluant:ethyl acetate:methanol=5:1) to give (2S,4S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (132 mg).

후처리

  1. temperatureWhile the mixture was chilled in an ice bath
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluant:ethyl acetate:methanol=5:1)

출처 및 근거

ORD 기록
ord-abd12d98ef3847688f3fd8778320c291
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08053465B2

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