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Acetic Acid → 1-({2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}amino)cyclopropanecarboxylic acid

HRID 1512926
ノート
印刷プレビュー

反応式

HRID 1512926 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[N:24]([CH3:26])[CH:23]=[C:22]4[CH2:27][CH:28]=O)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[NH2:30][C:31]1([C:34]([OH:36])=[O:35])[CH2:33][CH2:32]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[N:24]([CH3:26])[CH:23]=[C:22]4[CH2:27][CH2:28][NH:30][C:31]3([C:34]([OH:36])=[O:35])[CH2:33][CH2:32]3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 176Acetic AcidHCID 5351-Aminocyclopropane-1-carboxylic acidHCID 5049666Sodium triacetoxyborohydrideHCID 59146184HCID 59146184、化合物

生成物 1

HCID 445490351-({2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}amino)cyclopropanecarboxylic acid収率 13.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
20 °C

実験手順

To a stirred solution of [7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]acetaldehyde (D88) (50 mg), 1-aminocyclopropanecarboxylic acid (25 mg) and acetic acid (0.1 mL) in DCM (10 mL) was added sodium triacetoxyborohydride (52 mg). The reaction was stirred at 20° C. for 3 h. The mixture was concentrated and the residue was partitioned between ethyl acetate (25 mL) and aqueous HCl (2 M, 25 mL). The organic phase was washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulphate and evaporated to give the crude product, which was purified by Mass Directed Auto Prep to afford 1-({2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}amino)cyclopropanecarboxylic acid (E68) (8 mg, TFA salt). δH (DMSO-d6, 400 MHz): 1.36 (6H, d), 1.41 (4H, m), 3.06 (2H, t), 3.31 (2H, t), 3.65 (3H, s), 4.88 (1H, m), 7.22 (1H, t), 7.33 (1H, s), 7.46 (2H, m), 7.81 (1H, dd), 8.12 (1H, dd), 8.19 (1H, d). MS (ES): C26H27ClN4O4 requires 494; found 495.2 (M+H+).

後処理

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between ethyl acetate (25 mL) and aqueous HCl (2 M, 25 mL)
  3. washThe organic phase was washed with water (25 mL) and brine (25 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. customevaporated
  6. customto give the crude product, which
  7. customwas purified by Mass Directed Auto Prep

出典と根拠

ORDレコード
ord-524f7369af6641bf886e635d6db37d00
出典データセット
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08217028B2

反応ノート

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