N,N-二甲基甲酰胺 → 1-(9H-fluoren-9-yl)methyl 4-tert-butyl 2-(2-(2-bromophenylamino)-2-oxoethyl)piperazine-1,4-dicarboxylate

HRID 80486

反应方程式

HRID 80486 反应方程式
[Br:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[CH:9]1[C:21]2[CH:20]([CH2:22][O:23][C:24]([N:26]3[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH:27]3[CH2:39][C:40](O)=[O:41])=[O:25])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]=2[CH:12]=[CH:11][CH:10]=1.CN(C)C=O.Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1>[Br:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH:4][C:40](=[O:41])[CH2:39][CH:27]1[CH2:28][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:30][CH2:31][N:26]1[C:24]([O:23][CH2:22][CH:20]1[C:21]2[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=2[C:14]2[C:19]1=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:25]

参与物

6

反应物 4

HCID 6228N,N-二甲基甲酰胺HCID 11992邻溴苯胺HCID 27239391-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐HCID 27567964-Boc-1-Fmoc-2-哌嗪乙酸

产物 1

HCID 582849301-(9H-fluoren-9-yl)methyl 4-tert-butyl 2-(2-(2-bromophenylamino)-2-oxoethyl)piperazine-1,4-dicarboxylate

试剂、催化剂与溶剂 1

HCID 1049吡啶溶剂

实验过程

To a solution of 2-bromoaniline (3.69 g, 21.44 mmol), and 2-(1-(((9H-fluoren-9-yl)methoxy)carbonyl)-4-(tert-butoxycarbonyl)piperazin-2-yl)acetic acid (10 g, 21.44 mmol) in a 1:1 solution of N,N-dimethylformamide:pyridine (100 mL) was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (10.27 g, 53.6 mmol). The reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated and was subsequently washed with brine (3×) and 1M HCl (3×). The organic solution was then concentrated onto silica gel and purified via flash chromatography (10-70% ethyl acetate/hexanes) to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.43 (s, 1H), 7.81-7.95 (m, J=7.67 Hz, 2H), 7.53-7.75 (m, 4H), 7.22-7.48 (m, 5H), 7.10 (dd, J=7.21 Hz, 1H), 4.56 (s, 1H), 4.17-4.42 (m, 3H), 3.61-3.98 (m, 3H), 2.89-3.18 (m, 2H), 2.62-2.88 (m, 2H), 2.49-2.58 (m, 1H), 1.32-1.50 (m, 9H); MS (APCI+) m/z 522.2 (M-Boc+H)+.

后处理

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. washwas subsequently washed with brine (3×) and 1M HCl (3×)
  4. concentrationThe organic solution was then concentrated onto silica gel
  5. custompurified via flash chromatography (10-70% ethyl acetate/hexanes)

来源与证据

ORD记录
ord-4d002e6cd6ac470693aaf7f623afb94f
来源数据集
uspto-grants-2014_09
专利号
US08846663B2

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