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Isopropylamine → (R)-5-(6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl)-N-isopropyl-1,2,4-oxadiazole-3-carboxamide

HRID 2182912
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HRID 2182912 반응식
[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([O:22]CC)=O)[N:16]=2)[CH2:11][C:12]([OH:14])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:25]([NH2:28])([CH3:27])[CH3:26].CN1CCOCC1.ClC(OCC(C)C)=O.C[Si](C)(C)[O:46][NH2:47].FC(F)(F)C(O)=O>C(O)C.O>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([NH:28][CH:25]([CH3:27])[CH3:26])=[O:22])[N:16]=2)[CH2:11][C:12]([NH:47][OH:46])=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
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참가 물질

9

반응물 6

HCID 6363IsopropylamineHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 59909750(3R)-6-cyclohexyl-3-[3-(ethoxycarbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid

생성물 1

HCID 9947332
(R)-5-(6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl)-N-isopropyl-1,2,4-oxadiazole-3-carboxamide
수율 8%

시약·촉매·용매 2

HCID 702Ethanol용매2회HCID 962Water용매

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온도
80 °C

실험 절차

A solution of (3R)-6-cyclohexyl-3-[3-(ethoxycarbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid (Preparation 4) (500 mg, 1.47 mmol) in ethanol (13 ml) was treated with a solution of isopropylamine (434 mg, 7.35 mmol) in ethanol (2 ml) and the resulting mixture was heated at 80° C. under a nitrogen atmosphere for 10 hours. The solvent was removed under reduced pressure and the residue was dissolved in hydrochloric acid (1M, 10 ml) then extracted with ethyl acetate (×2). The combined organic layers were dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. This residue (531 mg) was then dissolved in dichloromethane (15 ml), cooled to 0° C. and treated sequentially with N-methylmorpholine (180 μ1.1.63 mmol) and isobutyl chloroformate (210 μl, 1.62 mmol). This mixture was stirred at 0° C. under a nitrogen atmosphere for 1 hour, then treated with O-(trimethylsilyl)hydroxylamine (220 μl, 1.80 mmol) and stirring continued for 10 minutes at 0° then for 17 hours at room temperature. The mixture was then treated with trifluoroacetic acid:water (5 ml, 9:1) and the solution stirred for 30 minutes. The solvent was removed under reduced pressure and the residue azeotroped from toluene (×2). The residue was purified by reverse phase HPLCa to afford the title compound as a foam (43 mg).

후처리

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in hydrochloric acid (1M, 10 ml)
  3. extractionthen extracted with ethyl acetate (×2)
  4. dry with materialThe combined organic layers were dried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. dissolutionThis residue (531 mg) was then dissolved in dichloromethane (15 ml)
  8. temperaturecooled to 0° C.
  9. stirringstirring
  10. waitcontinued for 10 minutes at 0°
  11. waitfor 17 hours at room temperature
  12. customThe solvent was removed under reduced pressure
  13. customthe residue azeotroped from toluene (×2)
  14. customThe residue was purified by reverse phase HPLCa

출처 및 근거

ORD 기록
ord-6f26653169cf4f519ce675f6ea6b356e
출처 데이터셋
uspto-grants-2005_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06897306B2

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