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1,2-Dimethoxyethane → {1-[5-(4'-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1'-phenyl-1',2',4',5'-tetrahydro-1H-[2,4']biimidazolyl-3'-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester

HRID 71813
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 71813
[CH3:1][O:2][C:3](=[O:34])[NH:4][CH:5]([C:9]([N:11]1[CH:15]([C:16]2[NH:17][CH:18]=[C:19]([C:21]3[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=3)[N:20]=2)[CH2:14][N:13]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].[CH3:35][O:36][C:37](=[O:70])[NH:38][CH:39]([C:43]([N:45]1[CH2:49][CH2:48][CH2:47][CH:46]1[C:50]1[NH:51][CH:52]=[C:53]([C:55]2[CH:60]=[CH:59][C:58](B3OC(C)(C)C(C)(C)O3)=[CH:57][CH:56]=2)[N:54]=1)=[O:44])[CH:40]([CH3:42])[CH3:41].C(=O)([O-])[O-].[K+].[K+].COCCOC>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.O>[CH3:1][O:2][C:3](=[O:34])[NH:4][CH:5]([C:9]([N:11]1[CH:15]([C:16]2[NH:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([C:58]4[CH:59]=[CH:60][C:55]([C:53]5[NH:54][C:50]([CH:46]6[CH2:47][CH2:48][CH2:49][N:45]6[C:43](=[O:44])[CH:39]([NH:38][C:37]([O:36][CH3:35])=[O:70])[CH:40]([CH3:42])[CH3:41])=[N:51][CH:52]=5)=[CH:56][CH:57]=4)=[CH:23][CH:22]=3)=[CH:18][N:17]=2)[CH2:14][N:13]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 178502159HCID 178502159, VerbindungHCID 178502203{1-[4-(4-Bromo-phenyl)-1'-phenyl-1',2',4',5'-tetrahydro-1H-[2,4]biimidazolyl-3'-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester

Produkt 1

HCID 66620324
{1-[5-(4'-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1'-phenyl-1',2',4',5'-tetrahydro-1H-[2,4']biimidazolyl-3'-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester
Ausbeute 8,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

{1-[4-(4-Bromo-phenyl)-1′-phenyl-1′,2′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (40 mg, 0.076 mmol) was combined with [2-Methyl-1-(2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (37.6 mg, 0.076 mmol) under an argon atmosphere. Potassium carbonate (20.9 mg, 0.152 mmol) and Pd(PPh3)4 (8.7 mg, 0.0076 mmol) were added, followed by DME (1.8 mL) and water (0.3 mL). The mixture was heated under microwave conditions for 20 minutes at 120° C. All volatiles were removed in vacuo and the crude material was dissolved in DMF and purified via RP-HPLC (eluent: water/MeCN w 0.1% TFA) to yield the product {1-[5-(4′-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1′-phenyl-1′,2′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (5.4 mg): LCMS-ESI+: calc'd for C45H53N9O6: 815.9 (M+). Found: 816.5 (M+H+); 1H-NMR: 300 MHz, (MeOH-d4) δ: 7.89-7.86 (m, 10H), 7.35 (m, 2H), 7.18 (m, 1H), 6.94 (m, 2H), 5.67 (m, 1H), 5.37 (m, 1H), 5.25 (m, 1H), 5.12 (m, 1H), 4.31-4.08 (m, 3H), 4.01-3.79 (m, 3H), 3.67 (s, 3H), 3.66 (s, 3H), 2.58 (m, 1H), 2.29-1.99 (m, 5H), 0.99-0.89 (m, 12H).

Aufarbeitung

  1. customAll volatiles were removed in vacuo
  2. dissolutionthe crude material was dissolved in DMF
  3. custompurified via RP-HPLC (eluent: water/MeCN w 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-d814101d4bf64d0db5e1c81c448320af
Quelldatensatz
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08822430B2

Notizen zur Reaktion

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