1,2-Dichloroethane → (1-(4-chlorobenzyl)-1H-indol-2-yl)(4-(isoindoline-2-carbonyl)piperidin-1-yl)methanone

HRID 83670ノート

反応式

HRID 83670 の反応式
[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16]([N:18]2[CH2:23][CH2:22][CH:21]([C:24](O)=[O:25])[CH2:20][CH2:19]2)=[O:17])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH2:52]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH2:54][NH:53]1>C(OCC)(=O)C.C(Cl)Cl>[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16]([N:18]2[CH2:19][CH2:20][CH:21]([C:24]([N:53]3[CH2:54][C:55]4[C:60](=[CH:59][CH:58]=[CH:57][CH:56]=4)[CH2:52]3)=[O:25])[CH2:22][CH2:23]2)=[O:17])=[CH:4][CH:3]=1

参加物

8

反応物 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 422478IsoindolineHCID 573857961-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carboxylic acid

生成物 1

HCID 68380199(1-(4-chlorobenzyl)-1H-indol-2-yl)(4-(isoindoline-2-carbonyl)piperidin-1-yl)methanone

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

The following was added sequentially to DCM (2 mL): 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carboxylic acid (50 mg, 0.126 mmol), DIPEA (0.07 mL, 0.378 mmol), EDC (30 mg, 0.151 mmol), HOBT (24 mg, 0.151 mmol), and isoindoline (0.018 mL, 0.151 mmol). The mixture was stirred for 18 h at rt, at which time the solution diluted with a 1:1 solution of ethyl acetate:diethyl ether and washed with 1M HCl (1×), 10% aq. sodium carbonate (1×) and brine (1×). The organic phase was dried with magnesium sulfate and concentrated in vacuo. The resulting residue was dissolved in EtOAc and precipitated out hexanes, and then collected over a filter and washed with a 10:1 solution of hexanes:ethyl acetate. (Yield: 22 mg, 0.044 mmol, 35%) 1H NMR (400 MHz, CDCl3) 7.65, 7.35-7.21, 7.15, 7.05, 6.68, 5.47, 4.77-4.17, 2.97, 2.76-2.64, 1.78, 1.47-1.34, 1.37-1.24, 0.95-0.83

後処理

  1. washdiethyl ether and washed with 1M HCl (1×), 10% aq. sodium carbonate (1×) and brine (1×)
  2. dry with materialThe organic phase was dried with magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resulting residue was dissolved in EtOAc
  5. customprecipitated out hexanes
  6. customcollected over
  7. filtrationa filter
  8. washwashed with a 10:1 solution of hexanes

出典と根拠

ORDレコード
ord-eb0ea9940d544aa58697eb0d50de74d8
出典データセット
uspto-grants-2014_09
特許番号
US08846684B2

反応ノート

読み込み中…