HRID79816

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)N1C2CCC(C2)C1c1nc2ccc(B3OC(C)(C)C(C)(C)O3)cc2[nH]1

HCID66620440

未命名化合物

结构：CC(C)(C)OC(=O)N1CCCC1c1ncc(-c2ccc3c(c2)sc2cc(Br)ccc23)[nH]1

HCID66620790

未命名化合物

结构：CC(C)(C)OC(=O)N1CCCC1c1ncc(-c2ccc3c(c2)sc2cc(-n4c(C5CC6CC5N(C(=O)OC(C)(C)C)C6)nc5ccccc54)ccc23)[nH]1

HCID86762795

未命名化合物

PRODUCTS

生成物

结构：CC(C)(C)OC(=O)N1CCCC1c1ncc(-c2ccc3c(c2)sc2cc(-c4ccc5nc(C6C7CCC(C7)N6C(=O)OC(C)(C)C)[nH]c5c4)ccc23)[nH]1

HCID66621194

未命名化合物

收率 70%

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

Ethyl acetate

C4H8O2

CONDITIONS

反应条件

温度: 80 °C

PROCEDURE

实验过程

3-(6-{(7-[2-(1-tert-Butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-dibenzothiophen-3-yl}-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester: A mixture of 2-[5-(7-Bromo-dibenzothiophen-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (300 mg, 0.48 mmol, 1 eq.), 3-[6-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-benzoimidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (1.1 eq., 530 mg), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (3%, 12 mg), tetrakis(triphenylphosphine)palladium (3%, 17 mg) and 2N potassium carbonate aqueous solution (3.3 eq., 0.8 mL) in 2 mL DME was heated to 80° C. under Argon for 5 hours. The reaction mixture was cooled and diluted in ethyl acetate and washed with saturated sodium bicarbonate solution. The organic layer dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexane) to give a yellow foam 3-(6-{7-[2-(1-tert-Butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-dibenzothiophen-3-yl}-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (245 mg, yield 70%). LCMS-ESI−: calc'd for C42H46N6O4S: 730.92. Found: 731.2 (M+H+).

WORKUP

后处理

temperatureThe reaction mixture was cooled
washwashed with saturated sodium bicarbonate solution
dry with materialThe organic layer dried (MgSO4)
concentrationconcentrated
custompurified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexane)

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-61f07669998140b792305a0229647db8
来源数据集: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
专利: US08841278B2
来源说明: uspto-grants-2014_09

反应 SMILES

C(OC(N1CC2CC1C(C1N(C3C=CC4C5C=CC([C:32]6[NH:33][C:34]([CH:37]7[CH2:41][CH2:40][CH2:39][N:38]7[C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])=[N:35][CH:36]=6)=CC=5SC=4C=3)C3C=CC=CC=3N=1)C2)=O)(C)(C)C.C(OC(N1CCCC1C1NC([C:71]2[CH:72]=[CH:73][C:74]3[C:78]4[CH:79]=[CH:80][C:81](Br)=[CH:82][C:77]=4[S:76][C:75]=3[CH:84]=2)=CN=1)=O)(C)(C)C.[C:85]([O:89][C:90]([N:92]1[CH:97]([C:98]2[NH:102][C:101]3[CH:103]=[C:104](B4OC(C)(C)C(C)(C)O4)[CH:105]=[CH:106][C:100]=3[N:99]=2)[CH:96]2[CH2:116][CH:93]1[CH2:94][CH2:95]2)=[O:91])([CH3:88])([CH3:87])[CH3:86].C(=O)([O-])[O-].[K+].[K+]>COCCOC.C(OCC)(=O)C.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].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:85]([O:89][C:90]([N:92]1[CH:97]([C:98]2[NH:102][C:101]3[CH:103]=[C:104]([C:81]4[CH:80]=[CH:79][C:78]5[C:74]6[CH:73]=[CH:72][C:71]([C:32]7[NH:33][C:34]([CH:37]8[CH2:41][CH2:40][CH2:39][N:38]8[C:42]([O:44][C:45]([CH3:46])([CH3:47])[CH3:48])=[O:43])=[N:35][CH:36]=7)=[CH:84][C:75]=6[S:76][C:77]=5[CH:82]=4)[CH:105]=[CH:106][C:100]=3[N:99]=2)[CH:96]2[CH2:116][CH:93]1[CH2:94][CH2:95]2)=[O:91])([CH3:88])([CH3:86])[CH3:87]