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Phosgene → 3-[(S)-(4-chlorophenyl)(3-{(1S)-2-fluoro-1-[3-fluoro-5-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)phenyl]-2-methylpropyl}azetidin-1-yl)methyl]benzonitrile

HRID 602996
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HRID 602996 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]#[N:36])[CH:30]=2)[N:9]2[CH2:12][CH:11]([C@@H:13]([C:18]3[CH:19]=[C:20]([CH:25]=[C:26]([F:28])[CH:27]=3)[C:21]([NH:23][NH2:24])=[O:22])[C:14]([F:17])([CH3:16])[CH3:15])[CH2:10]2)=[CH:4][CH:3]=1.[C:37](Cl)(Cl)=[O:38]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([N:9]2[CH2:12][CH:11]([C@@H:13]([C:18]3[CH:19]=[C:20]([C:21]4[O:22][C:37](=[O:38])[NH:24][N:23]=4)[CH:25]=[C:26]([F:28])[CH:27]=3)[C:14]([F:17])([CH3:16])[CH3:15])[CH2:10]2)[C:29]2[CH:30]=[C:31]([CH:32]=[CH:33][CH:34]=2)[C:35]#[N:36])=[CH:6][CH:7]=1
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참가 물질

4

반응물 2

HCID 6371PhosgeneHCID 670553323-((1S)-1-{1-[(S)-(4-chlorophenyl)(3-cyanophenyl)methyl]azetidin-3-yl}-2-fluoro-2-methylpropyl)-5-fluorobenzohydrazide

생성물 1

HCID 161137803-[(S)-(4-chlorophenyl)(3-{(1S)-2-fluoro-1-[3-fluoro-5-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)phenyl]-2-methylpropyl}azetidin-1-yl)methyl]benzonitrile

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 44 mg (0.86 mmol) of 3-((1S)-1-{1-[(S)-(4-chlorophenyl)(3-cyanophenyl) methyl]azetidin-3-yl}-2-fluoro-2-methylpropyl)-5-fluorobenzohydrazide (Preparation 19) in 2 mL CH2Cl2 was added 11.3 uL(0.215 mmol) of phosgene solution (20% in toluene) at 0° C., followed by stirring at rt. After 1.5 h, the solution was concentrated in vacuo to remove solvents and 2 mL of 2N NH3 in MeOH was added and the solution was concentrated again. The residue was purified by silica gel chromatography with CH2Cl2/acetone to afford the title compound as a white solid; 1H-NMR(CDCl3) δ 1.22(d, 3H, J=22 Hz), 1.28(d, 3H, J=22 Hz), 2.36 (t, 1H, J=8 Hz), 2.91 (t, 1H, J=8 Hz), 2.96 (m, 1H), 3.12 (t, 1H, J=7 Hz), 3.27 (m, 1H), 3.64 (t, 1H, J=6 Hz), 4.30 (s, 1H), 7.06-7.71 (m, 12H); Mass Spectrum: m/e=535 (M+1, 35Cl), 537 (M+1, 37Cl).

후처리

  1. concentrationthe solution was concentrated in vacuo
  2. customto remove solvents and 2 mL of 2N NH3 in MeOH
  3. additionwas added
  4. concentrationthe solution was concentrated again
  5. customThe residue was purified by silica gel chromatography with CH2Cl2/acetone

출처 및 근거

ORD 기록
ord-f789830e305c4316bbd37f7da6b8637e
출처 데이터셋
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07906652B2

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