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 79816노트

반응식

HRID 79816 반응식
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]

참가 물질

9

반응물 4

HCID 11430Potassium CarbonateHCID 66620440(1R,3S,4S)-3-[6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-yl]-2-azabicyclo[2.2.1]heptane-2-carboxylic acid 1,1-dimethylethyl esterHCID 666207902-[5-(7-Bromo-dibenzothiophen-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 867627956-{(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

생성물 1

HCID 666211943-(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 ester수율 70%

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

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+).

후처리

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

출처 및 근거

ORD 기록
ord-61f07669998140b792305a0229647db8
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841278B2

반응 노트

불러오는 중…