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 57473ノート

反応式

HRID 57473 の反応式
[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]

参加物

7

反応物 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

生成物 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-one収率 37%

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-9a8f5f89df9145229cd62d9401a20eea
出典データセット
uspto-grants-2016_09
特許番号
US09434719B2

反応ノート

読み込み中…