Potassium Carbonate → 3-(6-{7-[2-(5-benzyloxycarbonyl-5-aza-spiro[2.4]hept-6-yl)-3H-imidazol-4-yl]-dibenzofuran-3-yl}-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 2039300ノート

反応式

HRID 2039300 の反応式
[CH2:1]([O:8][C:9]([N:11]1[CH:17]([C:18]2[NH:19][C:20]([C:23]3[CH:24]=[CH:25][C:26]4[C:30]5[CH:31]=[CH:32][C:33](Br)=[CH:34][C:29]=5[O:28][C:27]=4[CH:36]=3)=[CH:21][N:22]=2)[CH2:16][C:13]2([CH2:15][CH2:14]2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:37]([O:41][C:42]([N:44]1[CH:49]([C:50]2[NH:54][C:53]3[CH:55]=[C:56](B4OC(C)(C)C(C)(C)O4)[CH:57]=[CH:58][C:52]=3[N:51]=2)[CH:48]2[CH2:68][CH:45]1[CH2:46][CH2:47]2)=[O:43])([CH3:40])([CH3:39])[CH3:38].C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.CCOC(C)=O.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:37]([O:41][C:42]([N:44]1[CH:49]([C:50]2[NH:54][C:53]3[CH:55]=[C:56]([C:33]4[CH:32]=[CH:31][C:30]5[C:26]6[CH:25]=[CH:24][C:23]([C:20]7[NH:19][C:18]([CH:17]8[CH2:16][C:13]9([CH2:14][CH2:15]9)[CH2:12][N:11]8[C:9]([O:8][CH2:1][C:2]8[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=8)=[O:10])=[N:22][CH:21]=7)=[CH:36][C:27]=6[O:28][C:29]=5[CH:34]=4)[CH:57]=[CH:58][C:52]=3[N:51]=2)[CH:48]2[CH2:68][CH:45]1[CH2:46][CH2:47]2)=[O:43])([CH3:39])([CH3:38])[CH3:40]

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 666209106-[5-(7-bromo-dibenzofuran-3-yl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester

生成物 1

HCID 666207913-(6-{7-[2-(5-benzyloxycarbonyl-5-aza-spiro[2.4]hept-6-yl)-3H-imidazol-4-yl]-dibenzofuran-3-yl}-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester収率 87.6%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To the solution of 6-[5-(7-bromo-dibenzofuran-3-yl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester (150 mg, 0.28 mmol) and 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 (160 mg, 0.36 mmol) in DME (2.25 ml) and water (0.75 ml) was added potassium carbonate (78 mg, 0.56 mmol), followed by Pd(PPh3)4 (15 mg) and PdCl2(dppf)CH2Cl2 (15 mg). The mixture was heated at 90 C for 16 hours. The mixture was diluted with EtOAc, and was washed with water and brine, and was dried with sodium sulfate. Concentration and purification by flash column chromatography (hexanes/EtOAc) gave 3-(6-{7-[2-(5-benzyloxycarbonyl-5-aza-spiro[2.4]hept-6-yl)-3H-imidazol-4-yl]-dibenzofuran-3-yl}-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (190 mg). m/z: 775.2 (M+1), 773.3 (M−1), 338.2 (M+2)/2.

後処理

  1. temperatureThe mixture was heated at 90 C for 16 hours
  2. washwas washed with water and brine
  3. dry with materialwas dried with sodium sulfate
  4. concentrationConcentration and purification by flash column chromatography (hexanes/EtOAc)

出典と根拠

ORDレコード
ord-119b4b19d40f4db281d449c8f879dd65
出典データセット
uspto-grants-2013_11
特許番号
US08575118B2

反応ノート

読み込み中…