Nitrogen → {4-[3-(3,4,5-Trimethoxy-phenyl)-propionyl]-piperazin-1-yl}-acetic acid ethyl ester

HRID 1944259

反応式

HRID 1944259 の反応式
N#N.CCN=C=NCCCN(C)C.Cl.CCN(CC)CC.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH2:34][CH2:35][C:36]([OH:38])=O)[CH:27]=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31].[CH2:39]([O:41][C:42]([CH2:44][N:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1)=[O:43])[CH3:40]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:39]([O:41][C:42](=[O:43])[CH2:44][N:45]1[CH2:50][CH2:49][N:48]([C:36](=[O:38])[CH2:35][CH2:34][C:26]2[CH:27]=[C:28]([O:32][CH3:33])[C:29]([O:30][CH3:31])=[C:24]([O:23][CH3:22])[CH:25]=2)[CH2:47][CH2:46]1)[CH3:40]

参加物

8

反応物 5

HCID 947NitrogenHCID 8471TriethylamineHCID 648603,4,5-Trimethoxyhydrocinnamic acidHCID 207112Ethyl piperazine-1-acetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

生成物 1

HCID 59785706{4-[3-(3,4,5-Trimethoxy-phenyl)-propionyl]-piperazin-1-yl}-acetic acid ethyl ester収率 83.1%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

The following reaction is done in an anhydrous N2 atmosphere.) Suspend EDC HCl (376 mg, 1.96 mmol) and Et3N (275 μL, 1.96 mmol) in anhydrous DCM (2.0 mL) and stir the resulting solution for 5 min at rt. Add 3-(3,4,5-Trimethoxy-phenyl)-propionic acid (346 mg, 1.44 mmol) and DMAP (17 mg, 0.14 mmol) and stir the resulting solution for 15 min. Add 1-(Ethoxycarbonylmethyl)piperazine (43) (224 mg, 1.30 mmol) and stir the reaction solution overnight at rt. Quench reaction solution with water, separate layers and extract aqu. layer with EtOAc (3 times). Filtrate the combined organic layer through a short pad of silica gel and remove solvent. Purify the crude product by preparative radial chromatography (silica gel, EtOAc/MeOH 9+1) to obtain {4-[3-(3,4,5-Trimethoxy-phenyl)-propionyl]-piperazin-1-yl}-acetic acid ethyl ester (45) (426 mg, 83%) as a colorless oil. 1H NMR (400 MHz, CDCl3): 1.26 (t, 3H, J=7.1 Hz); 2.45-2.70 (br.m, 6H); 2.89 (t, 2H, J=7.7 Hz); 3.26 (br.s, 2H); 3.43-3.56 (br.m, 2H); 3.61-3.76 (br.m, 2H); 3.80 (s, 3H); 3.83 (s, 6H); 4.18 (q, 2H, J=7.1 Hz); 6.41 (s, 2H).

後処理

  1. customThe following reaction
  2. customQuench
  3. customreaction solution with water
  4. customseparate layers
  5. extractionextract aqu
  6. customFiltrate the combined organic layer through a short pad of silica gel and remove solvent
  7. customPurify the crude product by preparative radial chromatography (silica gel, EtOAc/MeOH 9+1)

出典と根拠

ORDレコード
ord-945816a7e5ef4252bbabb7efdf079dc8
出典データセット
uspto-grants-2013_03
特許番号
US08394835B2

関連ノート

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