(+)-Glycidol → [4-((S)-2,3-dihydroxy-propyl)-piperazin-1-yl]-methanone

HRID 1894349노트

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HRID 1894349 반응식
C(C1N=C(OCC)C(C2N([C:35]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[O:36])C(C3C=CC(Cl)=CC=3)(C)C(C3C=CC(Cl)=CC=3)(C)N=2)=CN=1)(C)(C)C.[CH2:43]1[O:45][C@@H:44]1[CH2:46][OH:47]>C(O)C>[OH:45][C@H:44]([CH2:46][OH:47])[CH2:43][N:40]1[CH2:39][CH2:38][N:37]([CH:35]=[O:36])[CH2:42][CH2:41]1

참가 물질

4

반응물 2

HCID 5460455(+)-GlycidolHCID 67205751[2-(2-tert-Butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone

생성물 1

HCID 94253171[4-((S)-2,3-dihydroxy-propyl)-piperazin-1-yl]-methanone수율 185.9%

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
120 °C

실험 절차

The mixture of [2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (170 mg, 0.28 mmol) and R-glycidol (63 mg, 0.84 mmol) in ethanol (1 mL) was heated in the microwave at 120° C. for 10 min. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure. Purification of the crude residue by flash column chromatography (silica gel, eluting with 0-20% methanol in ethyl acetate) gave cis-2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-[4-((S)-2,3-dihydroxy-propyl)-piperazin-1-yl]-methanone (98 mg). The diastereomers were then separated by supercritical fluid chromatography (Berger Instrument Multi-Gram II, Daicel ChiralPak OD-H 3×25 cm, 35° C. at 100 bar, eluting with 25% ethanol in carbon dioxide) to give the title compound (post peak, 40 mg). HR-MS (ES, m/z) calculated for C35H45N6O4Cl2 [(M+H)+] 683.2874, observed 683.2871.

후처리

  1. temperatureUpon cooling to room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customPurification of the crude residue
  4. washby flash column chromatography (silica gel, eluting with 0-20% methanol in ethyl acetate)

출처 및 근거

ORD 기록
ord-76fcb015f9c84e778430dae66a92801d
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08513239B2

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