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 57473노트

반응식

HRID 57473 반응식
[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]

참가 물질

7

반응물 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

생성물 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-one수율 37%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9a8f5f89df9145229cd62d9401a20eea
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434719B2

반응 노트

불러오는 중…