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Cyanogen Bromide → 3-[(S)-(3-{(1S)-1-[3-(5-amino-1,3,4-oxadiazol-2-yl)-5-fluorophenyl]-2-fluoro-2-methylpropyl}azetidin-1-yl)(4-chlorophenyl)methyl]benzonitrile

HRID 602998
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HRID 602998 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([O-])(O)=O.[Na+].[N:42]#[C:43]Br>O1CCOCC1.O>[NH2:42][C:43]1[O:22][C:21]([C:20]2[CH:19]=[C:18]([C@H:13]([CH:11]3[CH2:12][N:9]([C@@H:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[C:29]4[CH:30]=[C:31]([CH:32]=[CH:33][CH:34]=4)[C:35]#[N:36])[CH2:10]3)[C:14]([F:17])([CH3:16])[CH3:15])[CH:27]=[C:26]([F:28])[CH:25]=2)=[N:23][N:24]=1
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참가 물질

6

반응물 3

HCID 10476Cyanogen BromideHCID 516892Sodium BicarbonateHCID 670553323-((1S)-1-{1-[(S)-(4-chlorophenyl)(3-cyanophenyl)methyl]azetidin-3-yl}-2-fluoro-2-methylpropyl)-5-fluorobenzohydrazide

생성물 1

HCID 667056803-[(S)-(3-{(1S)-1-[3-(5-amino-1,3,4-oxadiazol-2-yl)-5-fluorophenyl]-2-fluoro-2-methylpropyl}azetidin-1-yl)(4-chlorophenyl)methyl]benzonitrile

시약·촉매·용매 2

HCID 962
Water
용매
HCID 312751,4-Dioxane용매

실험 절차

To a mixture of 53 mg (0.104 mmol) of 3-((1S)-1-{1-[(S)-(4-chlorophenyl)(3-cyanophenyl) methyl]azetidin-3-yl}-2-fluoro-2-methylpropyl)-5-fluorobenzohydrazide in 3 mL of dioxane, 11.4 mg (0.135 mmol) of NaHCO3 in 1 mL of water was added 13 mg (0.125 mmol) cyanogen bromide and the solution was stirred at rt. After 2.5 h, it was concentrated to remove solvents. The residue was dissolved in 20 mL of CH2Cl2 and 5 mL of water and the pH was adjusted to 7-8 with aq NaHCO3. The aqueous layer was extracted with CH2Cl2, and the combined organic layer was concentrated. 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), 2.34 (br, 1H) 2.88 (br, 1H), 2.96 (m, 1H), 3.10 (dr, 1H), 3.24 (m, 1H), 3.63 (br, 1H), 4.27 (s, 1H), 5.50(s, 2H), 7.01-7.66 (m, 11H); Mass Spectrum: m/e=534 (M+1, 35Cl), 536 (M+1, 37Cl).

후처리

  1. concentrationit was concentrated
  2. customto remove solvents
  3. dissolutionThe residue was dissolved in 20 mL of CH2Cl2
  4. extractionThe aqueous layer was extracted with CH2Cl2
  5. concentrationthe combined organic layer was concentrated
  6. customThe residue was purified by silica gel chromatography with CH2Cl2/acetone

출처 및 근거

ORD 기록
ord-0cfabaf554cd443b8a058e0d2d1cade3
출처 데이터셋
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07906652B2

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