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 2039300노트

반응식

HRID 2039300 반응식
[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]

참가 물질

8

반응물 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

생성물 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 ester수율 87.6%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-119b4b19d40f4db281d449c8f879dd65
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575118B2

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