HRID1073188

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID8471

Triethylamine

C6H15N

HCID14722551

未命名化合物

结构：CNC(=O)C1CN(CC(=O)Nc2c(Cl)cc(C(C)=O)cc2Cl)CCN1

HCID14722753

未命名化合物

PRODUCTS

生成物

结构：CNC(=O)C1CN(CC(=O)Nc2c(Cl)cc(C(C)=O)cc2Cl)CCN1CCCCN(c1ccc(F)cc1)c1ccc(F)cc1

HCID14722700

未命名化合物

收率 19%

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID8019

2-Methoxyethanol

C3H8O2

CONDITIONS

反应条件

温度: 70 °C

PROCEDURE

实验过程

A mixture of 2.07 parts of N-(4-chlorobutyl)-4-fluoro-N-(4-fluorophenyl)benzenamine, 2.5 parts of N-(4-acetyl-2,6-dichlorophenyl)-3-[(methylamino)carbonyl]-1-piperazineacetamide, 1.3 parts of N,N-diethylethanamine and 97 parts of 2-methoxyethanol was stirred for 3 days at 70° C. The reaction mixture was evaporated and the residue was taken up in water. The product was extracted twice with dichloromethane. The combined extracts were washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The desired fraction was collected and the eluent was evaporated. The residue was crystallized from acetonitrlle. The product was filtered off and dried, yielding a first fraction of 0.74 parts (19.0%) of N-(4-acetyl-2.6-dichlorophenyl)-4-[4-[bis(4-fluorophenyl)amino]butyl]-3-[(methylamino)carbonyl]-1-piperazineacetamide mp. 87.1° C. The second fraction was collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding a second fraction of 0.78 parts (20.1%) of N-(4-acetyl-2,6-dichlorophenyl)-4-[4-[bis(4-fluorophenyl)amino]butyl]3-[(methylamino)carbonyl]-1-piperazineacetamide; mp. 85.0° C. Total yield: 1.52 parts (39.1%) of N-(4-acetyl-2,6-dichlorophenyl)-4-[4-[bis(4-fluorophenyl)amino]butyl]-3-[(methylamino)carbonyl]-1piperazineacetamide (compound 97).

WORKUP

后处理

customThe reaction mixture was evaporated
extractionThe product was extracted twice with dichloromethane
washThe combined extracts were washed with water
customdried
filtrationfiltered
customevaporated
customThe residue was purified by column chromatography over silica gel using
additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
customThe desired fraction was collected
customthe eluent was evaporated
customThe residue was crystallized from acetonitrlle
filtrationThe product was filtered off
customdried

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-b53c224b3c1048bfbdd19e0e7599d7c7
来源数据集: uspto-grants-1990_11
DOI: 10.6084/m9.figshare.5104873.v1
专利: US04968684
来源说明: uspto-grants-1990_11

反应 SMILES

Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1.[C:21]([C:24]1[CH:29]=[C:28]([Cl:30])[C:27]([NH:31][C:32](=[O:44])[CH2:33][N:34]2[CH2:39][CH2:38][NH:37][CH:36]([C:40]([NH:42][CH3:43])=[O:41])[CH2:35]2)=[C:26]([Cl:45])[CH:25]=1)(=[O:23])[CH3:22].C(N(CC)CC)C>COCCO>[C:21]([C:24]1[CH:29]=[C:28]([Cl:30])[C:27]([NH:31][C:32](=[O:44])[CH2:33][N:34]2[CH2:39][CH2:38][N:37]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[C:7]3[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=3)[CH:36]([C:40]([NH:42][CH3:43])=[O:41])[CH2:35]2)=[C:26]([Cl:45])[CH:25]=1)(=[O:23])[CH3:22]