Diisopropylethylamine → (R)-4-((R)-1-tert-butoxyethyl)-3-(2-((S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethylamino)-6-(difluoromethyl)pyrimidin-4-yl)oxazolidin-2-one

HRID 57473Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 57473
[C:1]([O:5][C@@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]1[CH:19]=[C:18]([CH:20]([F:22])[F:21])[N:17]=[C:16](S(C)(=O)=O)[N:15]=1)[CH3:7])([CH3:4])([CH3:3])[CH3:2].[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[N:38]=[C:37]([C@@H:39]([NH2:41])[CH3:40])[O:36][N:35]=2)=[CH:30][CH:29]=1.C(N(C(C)C)C(C)C)C>CS(C)=O.C(Cl)Cl.O>[C:1]([O:5][C@@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]1[CH:19]=[C:18]([CH:20]([F:22])[F:21])[N:17]=[C:16]([NH:41][C@H:39]([C:37]2[O:36][N:35]=[C:34]([C:31]3[CH:32]=[CH:33][C:28]([Cl:27])=[CH:29][CH:30]=3)[N:38]=2)[CH3:40])[N:15]=1)[CH3:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 3

HCID 81531DiisopropylethylamineHCID 40800146(1S)-1-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]ethan-1-amineHCID 90417088(R)-4-((R)-1-tert-butoxyethyl)-3-(6-(difluoromethyl)-2-(methylsulfonyl)pyrimidin-4-yl)oxazolidin-2-one

Produkt 1

HCID 90414149(R)-4-((R)-1-tert-butoxyethyl)-3-(2-((S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethylamino)-6-(difluoromethyl)pyrimidin-4-yl)oxazolidin-2-oneAusbeute 37 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of (R)-4-((R)-1-tert-butoxyethyl)-3-(6-(difluoromethyl)-2-(methylsulfonyl)pyrimidin-4-yl)oxazolidin-2-one (0.146 g, 0.371 mmol), (S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethanamine (91 mg, 0.41 mmol, 1.1 equiv), and N-ethyl-N-isopropylpropan-2-amine (0.097 mL, 0.56 mmol, 1.5 equiv) in DMSO (2.0 mL) was heated at 85° C. for 18 h. The reaction was cooled to room temperature and diluted with DCM (20 mL) and water (20 mL). The layers were separated and the aqueous layer was extracted with DCM (20 mL). The combined organic layers were washed with saturated aqueous NaCl (10 mL), dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane 20% to 60%) provided (R)-4-((R)-1-tert-butoxyethyl)-3-(2-((S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethylamino)-6-(difluoromethyl)pyrimidin-4-yl)oxazolidin-2-one as a yellow oily solid in 37% yield. MS m/z 537.2 (M+H)+; Rt-1.22 min.

Aufarbeitung

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with DCM (20 mL)
  3. washThe combined organic layers were washed with saturated aqueous NaCl (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-9a8f5f89df9145229cd62d9401a20eea
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434719B2

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