HRID71733

反应详情

EQUATION

反应方程式

REACTANTS

反应物

结构：CC(C)(C)OC(=O)N1CCCC1c1nc2ccc(Br)cc2[nH]1

HCID58185275

未命名化合物

结构：CC(C)(C)OC(=O)N1CCCC1c1ncc(-c2ccc(-c3ccc(B4OC(C)(C)C(C)(C)O4)s3)cc2)[nH]1

HCID66620980

未命名化合物

PRODUCTS

生成物

结构：CC(C)(C)OC(=O)N1CCCC1c1nc2ccc(-c3ccc(-c4ccc(-c5cnc(C6CCCN6C=O)[nH]5)cc4)s3)cc2[nH]1

HCID86648874

未命名化合物

收率 66.2%

AUXILIARIES

试剂、催化剂与溶剂

结构：c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1

催化剂HCID178418397

未命名化合物

溶剂HCID8071

未命名化合物

溶剂HCID8857

Ethyl acetate

C4H8O2

溶剂HCID11430

Potassium Carbonate

CK2O3

CONDITIONS

反应条件

温度: 110 °C

PROCEDURE

实验过程

A mixture of 2-(5-{4-[5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiophen-2-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.110 g), 2-(6-Bromo-1H-benzoimidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.115 g) and Pd(PPh3)4 (0.012 g) in 2.0M potassium carbonate solution (0.32 mL) and dimethoxyethane (0.64 mL) was heated in microwave at 110° C. for 30 minutes. Reaction mixture was cooled, diluted with ethyl acetate, washed with brine, dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 50 to 100% ethyl acetate/hexanes) and preparative reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA) to give 2-[6-(5-{4-[2-(1-Formyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-phenyl}-thiophen-2-yl)-1H-benzoimidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.085 g) as a bis-TFA salt: LCMS-ESI+: calc'd for C38H45N6O4S: 681.86 (M+H+). Found: 681.0 (M+H+).

WORKUP

后处理

customReaction mixture
temperaturewas cooled
washwashed with brine
dry with materialdried (MgSO4)
concentrationconcentrated
custompurified by flash column chromatography (silica gel, 50 to 100% ethyl acetate/hexanes) and preparative reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA)

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-9725bed0fd41465b8c186e1b1e96ed9c
来源数据集: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
专利: US08822430B2
来源说明: uspto-grants-2014_09

反应 SMILES

C([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[S:25][C:26](B4OC(C)(C)C(C)(C)O4)=[CH:27][CH:28]=3)=[CH:20][CH:19]=2)=[CH:16][N:17]=1)=O)(C)(C)C.[C:38]([O:42][C:43]([N:45]1[CH2:49][CH2:48][CH2:47][CH:46]1[C:50]1[NH:54][C:53]2[CH:55]=[C:56](Br)[CH:57]=[CH:58][C:52]=2[N:51]=1)=[O:44])([CH3:41])([CH3:40])[CH3:39]>C(=O)([O-])[O-].[K+].[K+].C(COC)OC.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:38]([O:42][C:43]([N:45]1[CH2:49][CH2:48][CH2:47][CH:46]1[C:50]1[NH:54][C:53]2[CH:55]=[C:56]([C:26]3[S:25][C:24]([C:21]4[CH:22]=[CH:23][C:18]([C:15]5[NH:14][C:13]([CH:9]6[CH2:10][CH2:11][CH2:12][N:8]6[CH:6]=[O:5])=[N:17][CH:16]=5)=[CH:19][CH:20]=4)=[CH:28][CH:27]=3)[CH:57]=[CH:58][C:52]=2[N:51]=1)=[O:44])([CH3:41])([CH3:40])[CH3:39]