HRID1185693

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID11430

Potassium Carbonate

CK2O3

结构：CC(C)(C)OC(=O)N1CCCC1c1ncc(Br)n1COCC[Si](C)(C)C

HCID57420213

未命名化合物

结构：CC(C)(C)OC(=O)N1CCCC1c1nc2ccc(-c3ccc(-c4ccc(B5OC(C)(C)C(C)(C)O5)cc4)cc3)cc2[nH]1

HCID66620202

未命名化合物

PRODUCTS

生成物

结构：CC(C)(C)OC(=O)N1CCCC1c1nc2ccc(-c3ccc(-c4ccc(-c5cnc(C6CCCN6C(=O)OC(C)(C)C)n5COCC[Si](C)(C)C)cc4)cc3)cc2[nH]1

HCID66620381

未命名化合物

收率 25%

AUXILIARIES

试剂、催化剂与溶剂

结构：Cl[Pd]Cl.[Fe+2].c1ccc(P(c2ccccc2)[c-]2cccc2)cc1.c1ccc(P(c2ccccc2)[c-]2cccc2)cc1

催化剂HCID178418228

Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)

C34H28Cl2FeP2Pd

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HCID962

Water

H2O

溶剂HCID8071

未命名化合物

溶剂HCID8857

Ethyl acetate

C4H8O2

CONDITIONS

反应条件

温度: 90 °C

PROCEDURE

实验过程

A mixture of 2-{6-[4′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-biphenyl-4-yl]-1H-benzoimidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (147 mg, 0.26 mmol), 2-[5-bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (116 mg, 0.26 mmol), tetrakis(triphenylphosphine)palladium (30 mg, 0.026 mmol), Pd(dppf)Cl2 (21 mg, 0.026 mmol) and potassium carbonate (72 mg, 0.52 mmol) in 3 ml 1,2-dimethoxyethane and 1 mL water was heated to 90° C. for 2.5 hours. The reaction mixture was cooled and dissolved in ethyl acetate and washed with 5% lithium chloride aqueous solution. The organic layer was dried (MgSO4), concentrated and purified by preparative reverse phase HPLC (GEMINI, 5 to 100% ACN/H2O+0.1% TFA). Product was lyophilized to give 2-(6-{4′-[2-(1-Boc-pyrrolidin-2-yl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-biphenyl-4-yl}-1H-benzoimidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (52 mg, yield 25%); LCMS-ESI+: calc'd for C46H60N6O5Si: 805.09. Found: 805.1 (M+H+).

WORKUP

后处理

temperatureThe reaction mixture was cooled
washwashed with 5% lithium chloride aqueous solution
dry with materialThe organic layer was dried (MgSO4)
concentrationconcentrated
custompurified by 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-4cfbad6e57194116be9a8e0d1b71ad79
来源数据集: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
专利: US08669234B2
来源说明: uspto-grants-2014_03

反应 SMILES

[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:17][C:16]2[CH:18]=[C:19]([C:22]3[CH:27]=[CH:26][C:25]([C:28]4[CH:33]=[CH:32][C:31](B5OC(C)(C)C(C)(C)O5)=[CH:30][CH:29]=4)=[CH:24][CH:23]=3)[CH:20]=[CH:21][C:15]=2[N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:43]([O:47][C:48]([N:50]1[CH2:54][CH2:53][CH2:52][CH:51]1[C:55]1[N:56]([CH2:61][O:62][CH2:63][CH2:64][Si:65]([CH3:68])([CH3:67])[CH3:66])[C:57](Br)=[CH:58][N:59]=1)=[O:49])([CH3:46])([CH3:45])[CH3:44].C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.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.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:17][C:16]2[CH:18]=[C:19]([C:22]3[CH:23]=[CH:24][C:25]([C:28]4[CH:29]=[CH:30][C:31]([C:57]5[N:56]([CH2:61][O:62][CH2:63][CH2:64][Si:65]([CH3:68])([CH3:67])[CH3:66])[C:55]([CH:51]6[CH2:52][CH2:53][CH2:54][N:50]6[C:48]([O:47][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:49])=[N:59][CH:58]=5)=[CH:32][CH:33]=4)=[CH:26][CH:27]=3)[CH:20]=[CH:21][C:15]=2[N:14]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]