Diisopropylethylamine → (2S,4S)-1-[[N-[4-(2-tetrahydropyranyl)oxycarbonylbicyclo[2,2,2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

HRID 2109489노트

반응식

HRID 2109489 반응식
[NH2:1][C:2]12[CH2:9][CH2:8][C:5]([C:10]([O:12][CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][O:14]3)=[O:11])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.C(N(C(C)C)CC)(C)C.Br[CH2:29][C:30]([N:32]1[CH2:36][C@@H:35]([F:37])[CH2:34][C@H:33]1[C:38]#[N:39])=[O:31]>C(#N)C>[O:14]1[CH2:15][CH2:16][CH2:17][CH2:18][CH:13]1[O:12][C:10]([C:5]12[CH2:6][CH2:7][C:2]([NH:1][CH2:29][C:30]([N:32]3[CH2:36][C@@H:35]([F:37])[CH2:34][C@H:33]3[C:38]#[N:39])=[O:31])([CH2:9][CH2:8]1)[CH2:3][CH2:4]2)=[O:11]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 21090395(2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrileHCID 231496982-Tetrahydropyranyl 4-aminobicyclo[2,2,2]octane-1-carboxylate

생성물 1

HCID 59383132(2S,4S)-1-[[N-[4-(2-tetrahydropyranyl)oxycarbonylbicyclo[2,2,2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile수율 79.6%

시약·촉매·용매 1

HCID 6342Acetonitrile용매2회

실험 절차

2-Tetrahydropyranyl 4-aminobicyclo[2,2,2]octane-1-carboxylate (62.9 mg) was suspended in acetonitrile (1 mL). To this suspension, diisopropylethylamine (47 μL) was added. With the solution chilled in an ice bath, (2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile (53.1 mg) in acetonitrile (0.8 mL) was added and the mixture was stirred for 4 hours. Subsequently, the reaction mixture was concentrated, and ethyl acetate and water were added to dissolve the residue. To this solution, an aqueous sodium bicarbonate solution was added to make the solution basic and the solution 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 resulting residue was purified by silica gel column chromatography (eluant: dichloromethane: methanol=10:1) to obtain (2S,4S)-1-[[N-[4-(2-tetrahydropyranyl)oxycarbonylbicyclo[2,2,2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (73.3 mg).

후처리

  1. temperatureWith the solution chilled in an ice bath
  2. concentrationSubsequently, the reaction mixture was concentrated
  3. additionethyl acetate and water were added
  4. dissolutionto dissolve the residue
  5. additionTo this solution, an aqueous sodium bicarbonate solution was added
  6. extractionthe solution was extracted with ethyl acetate
  7. washThe ethyl acetate layer was washed with saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by silica gel column chromatography (eluant: dichloromethane: methanol=10:1)

출처 및 근거

ORD 기록
ord-de444184e7f946ecb15bbd9aa35be9ea
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07514571B2

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