HRID2405552

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID12734

Diisopropylcarbodiimide

C7H14N2

HCID85082

L-Alanine, N-[(1,1-dimethylethoxy)carbonyl]-

C8H15NO4

结构：CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C.[NH-]CCCO

HCID131731275

未命名化合物

PRODUCTS

生成物

结构：CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C.C[C@H](NC(=O)OC(C)(C)C)C(=O)O.[NH-]CCCO

HCID131731276

未命名化合物

收率 75%

AUXILIARIES

试剂、催化剂与溶剂

催化剂HCID14284

N,N-Dimethylpyridin-4-amine

C7H10N2

溶剂HCID6344

Dichloromethane

CH2Cl2

CONDITIONS

反应条件

温度: 0 °C

PROCEDURE

实验过程

BOC-L-alanine (117.0 mg, 0.618 mmol) and DMAP (94.0 mg, 0.772 mmol) were taken up in dichloromethane and then diisopropylcarbodiimide (52.6 μL, 0.340 mmol) was added. The reaction mixture was cooled to 0° C. and stirred for 10 minutes after which auristatin F-hydroxypropylamide (124 mg, 0.154 mmol, prepared as described in Example 48) was added. The reaction mixture was warmed to 23° C. and stirred for 18 hours. Purification via preparative HPLC followed by removal of the water via lyophilization afforded the title compound as beige solid (112 mg, 75% yield).

WORKUP

后处理

additionwas added
temperatureThe reaction mixture was warmed to 23° C.
customPurification via preparative HPLC
customfollowed by removal of the water via lyophilization

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-1de9dccca7ed43b48269df2328cee150
来源数据集: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
专利: US08808679B2
来源说明: uspto-grants-2014_08

反应 SMILES

[C:1]([NH:8][C@H:9]([C:11]([OH:13])=[O:12])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N=C=NC(C)C)(C)C.[CH3:23][CH2:24][C@@H:25]([C@H:27]([N:58]([C:60]([C@@H:62]([NH:66][C:67]([C@@H:69]([N:73]([CH3:75])[CH3:74])[CH:70]([CH3:72])[CH3:71])=[O:68])[CH:63]([CH3:65])[CH3:64])=[O:61])[CH3:59])[C@H:28]([O:56][CH3:57])[CH2:29][C:30]([N:32]1[C@H:36]([C@H:37]([O:54][CH3:55])[C@H:38]([C:40]([NH:42][C@H:43]([C:51]([OH:53])=[O:52])[CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:41])[CH3:39])[CH2:35][CH2:34][CH2:33]1)=[O:31])[CH3:26].[OH:76][CH2:77][CH2:78][CH2:79][NH-:80]>CN(C1C=CN=CC=1)C.ClCCl>[CH3:23][CH2:24][C@@H:25]([C@H:27]([N:58]([C:60]([C@@H:62]([NH:66][C:67]([C@@H:69]([N:73]([CH3:75])[CH3:74])[CH:70]([CH3:72])[CH3:71])=[O:68])[CH:63]([CH3:65])[CH3:64])=[O:61])[CH3:59])[C@H:28]([O:56][CH3:57])[CH2:29][C:30]([N:32]1[C@H:36]([C@H:37]([O:54][CH3:55])[C@H:38]([C:40]([NH:42][C@H:43]([C:51]([OH:53])=[O:52])[CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:41])[CH3:39])[CH2:35][CH2:34][CH2:33]1)=[O:31])[CH3:26].[C:1]([NH:8][C@H:9]([C:11]([OH:13])=[O:12])[CH3:10])([O:3][C:4]([CH3:7])([CH3:5])[CH3:6])=[O:2].[OH:76][CH2:77][CH2:78][CH2:79][NH-:80]