1,2-Dichloroethane → (1-(4-fluorobenzyl)-1H-indol-2-yl)(4-(hydroxymethyl)piperidin-1-yl)methanone

HRID 83661노트

반응식

HRID 83661 반응식
[F:1][C:2]1[CH:20]=[CH:19][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](O)=[O:17])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH:44]1[CH2:49][CH2:48][CH:47]([CH2:50][OH:51])[CH2:46][CH2:45]1>CN(C=O)C>[F:1][C:2]1[CH:20]=[CH:19][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:44]2[CH2:49][CH2:48][CH:47]([CH2:50][OH:51])[CH2:46][CH2:45]2)=[O:17])=[CH:4][CH:3]=1

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 4207714-PiperidinemethanolHCID 186270691-(4-fluorobenzyl)-1H-indole-2-carboxylic acid

생성물 1

HCID 68380165(1-(4-fluorobenzyl)-1H-indol-2-yl)(4-(hydroxymethyl)piperidin-1-yl)methanone

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

The following was added sequentially to DMF (10 mL): 1-(4-fluorobenzyl)-1H-indole-2-carboxylic acid (1.175 g, 4.36 mmol), DIPEA (2.29 mL, 13.09 mmol), EDC (1.00 g, 5.24 mmol), and HOBT (802 mg, 5.24 mmol). This solution was allowed to stir at rt for 1.5 h, at which time 4-piperidinemethanol (754 mg, 6.55 mmol) was added. Stirring continued for 22 h at rt, at which time the solution was partitioned between water and 1:1 solution of ethyl acetate:diethyl ether. The organic extract was then washed with saturated aq. sodium carbonate, dried with magnesium sulfate, and concentrated in vacuo. Purification was accomplished via silica gel flash chromatography (100 g silica, 80% EtOAc/Hexanes.) Resulting residue was crystallized via diethyl ether/hexane trituration to give the title compound as a white solid. (Yield: 1.507 g, 4.11 mmol, 94%) 1H NMR (400 MHz, CDCl3) 7.63, 7.37, 7.28-7.22, 7.14, 7.08, 6.91, 6.60, 5.46, 4.65, 4.13, 3.42, 2.76, 1.76-1.54, 1.05, 0.71

후처리

  1. additionwas added
  2. customthe solution was partitioned between water and 1:1 solution of ethyl acetate
  3. extractionThe organic extract
  4. washwas then washed with saturated aq. sodium carbonate
  5. dry with materialdried with magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification
  8. customResulting residue
  9. customwas crystallized via diethyl ether/hexane trituration

출처 및 근거

ORD 기록
ord-988840caadea41feb7621ebd8dee6997
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846684B2

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