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

HRID 83670노트

반응식

HRID 83670 반응식
[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

참가 물질

8

반응물 5

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

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

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

후처리

  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

출처 및 근거

ORD 기록
ord-eb0ea9940d544aa58697eb0d50de74d8
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846684B2

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