Potassium Carbonate → 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

HRID 79816Notes

Reaction equation

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]

Participants

Conditions

Temperature: 80 °C

Procedure

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

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)

Sources & evidence

ORD record: ord-61f07669998140b792305a0229647db8
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841278B2

Reaction notes

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