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 72054Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 72054
[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]

Komponenten

8

Edukt 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

Produkt 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 esterAusbeute 87,6 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-dea9b363f59841d182eaf84729b5a103
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822430B2

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