1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-{3-[2-(Hydroxymethyl)-1H-indol-5-yl]-1,2,4-oxadiazol-5-yl}-2-[(1-methylethyl)oxy]benzonitrile

HRID 1512872ノート

反応式

HRID 1512872 の反応式
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[C:22]([C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH:34]([CH3:36])[CH3:35])[C:27]([OH:29])=O)#[N:23].O[NH:38][C:39]([C:41]1[CH:42]=[C:43]2[C:47](=[CH:48][CH:49]=1)[NH:46][C:45]([CH2:50][OH:51])=[CH:44]2)=[NH:40]>CN(C=O)C.CCOC(C)=O>[OH:51][CH2:50][C:45]1[NH:46][C:47]2[C:43]([CH:44]=1)=[CH:42][C:41]([C:39]1[N:40]=[C:27]([C:26]3[CH:30]=[CH:31][C:32]([O:33][CH:34]([CH3:36])[CH3:35])=[C:24]([CH:25]=3)[C:22]#[N:23])[O:29][N:38]=1)=[CH:49][CH:48]=2

参加物

7

反応物 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 21956832RP-101124HCID 178513239HCID 178513239、化合物

生成物 1

HCID 445474645-{3-[2-(Hydroxymethyl)-1H-indol-5-yl]-1,2,4-oxadiazol-5-yl}-2-[(1-methylethyl)oxy]benzonitrile収率 26.6%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

EDCI (144 mg) and HOBT (104 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described on WO2005/58848, 144 mg) in DMF (5 mL) at RT. The resulting solution was stirred for 15 min. N-Hydroxy-2-(hydroxymethyl)-1H-indole-5-carboximidamide (D25) (144 mg) was added and the reaction mixture was stirred at RT for 1 hour. The reaction mixture was heated to 80° C. and stirred at that temperature for 4 hours. EtOAc (50 mL) was added and the organic solution was washed with water (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and water (50 mL). The organic fraction was dried over anhydrous magnesium sulfate. The dried solution was concentrated. The residue was recrystallized from EtOAc/ether to afford 5-{3-[2-(hydroxymethyl)-1H-indol-5-yl]-1,2,4-oxadiazol-5-yl}-2-[(1-methylethyl)oxy]benzonitrile (E12) (70 mg) as a light brown solid. δH (DMSO-d6, 400 MHz): 1.39 (6H, d), 4.65 (2H, d), 4.99 (1H, m), 5.36 (1H, t), 6.46 (1H, s), 7.49 (1H, d), 7.56 (1H, d), 7.79 (1H, dd), 8.28 (1H, dd), 8.42 (1H, d), 8.52 (1H, d), 11.43 (1H, s). MS (ES): C21H18N4O3 requires 374; found 375.0 (M+H+).

後処理

  1. stirringthe reaction mixture was stirred at RT for 1 hour
  2. stirringstirred at that temperature for 4 hours
  3. washthe organic solution was washed with water (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and water (50 mL)
  4. dry with materialThe organic fraction was dried over anhydrous magnesium sulfate
  5. concentrationThe dried solution was concentrated
  6. customThe residue was recrystallized from EtOAc/ether

出典と根拠

ORDレコード
ord-4066b8ad42b942e08bfbdd89068b70a2
出典データセット
uspto-grants-2012_07
特許番号
US08217028B2

反応ノート

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