1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 2405953ノート

反応式

HRID 2405953 の反応式
[CH3:1][C:2]([S:19]([CH3:22])(=[O:21])=[O:20])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:10]=[CH:9]1)[C:3]([OH:5])=O.CCN=C=NCCCN(C)C.C1C=CC2[N:42]([OH:43])N=NC=2C=1.[O:44]1[CH2:49][CH2:48][CH2:47][CH2:46][CH:45]1NO>C(Cl)Cl.O>[CH3:1][C:2]([S:19]([CH3:22])(=[O:21])=[O:20])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:10]=[CH:9]1)[C:3]([NH:42][O:43][CH:45]1[CH2:46][CH2:47][CH2:48][CH2:49][O:44]1)=[O:5]

参加物

7

反応物 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 13168123Tetrahydropyranyl hydroxylamineHCID 708175182-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)butanoic acid

生成物 1

HCID 867102522-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide収率 6%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of 2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)butanoic acid (304.6 mg, 0.945 mmol, 1 eq) in DCM (10 mL) was added TEA (172 mg, 1.70 mmol, 0.237 mL, 1.80 eq), EDCI (254 mg, 1.32 mmol, 1.4 eq), HOBT (260 mg 1.70 mmol, 1.80 eq) and O— tetrahydro-2-H-pyran-2-ylhydroxylamine (166 mg, 1.42 mmol, 1.5 eq). The reaction was allowed stir at RT overnight. The reaction mixture was diluted with DCM and water. The aqueous layer was extracted several times with DCM and the combined organic layers were dried (MgSO4), filtered and concentrated. The crude product mixture was absorbed onto silica gel and purified by flash chromatrography on silica gel eluting with an EtOAc-heptane gradient to give 2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (24 mg, 6% yield). LC-MS M+H+422.6.

後処理

  1. extractionThe aqueous layer was extracted several times with DCM
  2. dry with materialthe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product mixture was absorbed onto silica gel
  6. custompurified by flash chromatrography on silica gel eluting with an EtOAc-heptane gradient

出典と根拠

ORDレコード
ord-2235fbe2387e4b26a8fd0a1bbea7beec
出典データセット
uspto-grants-2014_08
特許番号
US08809333B2

反応ノート

読み込み中…