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 417565ノート

反応式

HRID 417565 の反応式
[C:1]([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:19]=[CH:20][C:21]3[C:25]4[CH:26]=[CH:27][C:28](Br)=[CH:29][C:24]=4[S:23][C:22]=3[CH:31]=2)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC([N:39]1[CH:44]([C:45]2[NH:49][C:48]3[CH:50]=[C:51](B4OC(C)(C)C(C)(C)O4)[CH:52]=[CH:53][C:47]=3[N:46]=2)[CH:43]2[CH2:63][CH:40]1[CH2:41][CH2:42]2)=O)(C)(C)C.[C:64](=[O:67])([O-:66])[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:1]([O:66][C:64]([N:39]1[CH:44]([C:45]2[NH:46][C:47]3[CH:53]=[C:52]([C:28]4[CH:27]=[CH:26][C:25]5[C:21]6[CH:20]=[CH:19][C:18]([C:15]7[NH:14][C:13]([CH:9]8[CH2:10][CH2:11][CH2:12][N:8]8[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[N:17][CH:16]=7)=[CH:31][C:22]=6[S:23][C:24]=5[CH:29]=4)[CH:51]=[CH:50][C:48]=3[N:49]=2)[CH:43]2[CH2:63][CH:40]1[CH2:41][CH2:42]2)=[O:67])([CH3:4])([CH3:3])[CH3:2]

参加物

8

反応物 3

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 ester

生成物 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 ester収率 70%

試薬・触媒・溶媒 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-31142fcf8f85471eb88e3a90b7a85b02
出典データセット
uspto-grants-2012_01
特許番号
US08088368B2

反応ノート

読み込み中…