Cesium carbonate → tert-Butyl 6-(7-chloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-carboxylate

HRID 1910684Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1910684
Cl[C:2]1[C:3]2[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:4]=2[N:5]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[C:6](=[O:18])[CH:7]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])[N:8]=1.[O:33]=[C:34]1[N:51](C(OC(C)(C)C)=O)[C:37]2=[N:38][CH:39]=[C:40](B3OC(C)(C)C(C)(C)O3)[CH:41]=[C:36]2[N:35]1[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60].C(=O)([O-])[O-].[Cs+].[Cs+].[Cl-].[Li+]>O1CCOCC1.O>[Cl:32][C:30]1[CH:29]=[CH:28][C:4]2[N:5]([CH2:19][C:20]3[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=3)[C:6](=[O:18])[CH:7]([CH2:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:17])[N:8]=[C:2]([C:40]3[CH:41]=[C:36]4[N:35]([C:59]([O:61][C:62]([CH3:63])([CH3:64])[CH3:65])=[O:60])[C:34](=[O:33])[NH:51][C:37]4=[N:38][CH:39]=3)[C:3]=2[CH:31]=1

Komponenten

6

Edukt 4

HCID 10796Cesium carbonateHCID 433294Lithium ChlorideHCID 67282666di-tert-butyl 2-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazo[4,5-b]pyridine-1,3(2H)-dicarboxylateHCID 672834205,7-Dichloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

Produkt 1

HCID 67471943tert-Butyl 6-(7-chloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-carboxylateAusbeute 26,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

5,7-Dichloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (245 mg) and di-tert-butyl 2-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazo[4,5-b]pyridine-1,3(2H)-dicarboxylate (255 mg, 1.1 eq) were dissolved in dioxane/water (2 mL:0.65 mL), and cesium carbonate (327 mg, 2 eq) was added followed by lithium chloride (64 mg, 3 eq). The mixture was degassed with nitrogen and then tetrakis-triphenylphosphine palladium (0) (58 mg, 0.1 eq) was added. The mixture was degassed again, and the reaction was then heated to 80° C. for three hours. The crude mixture was partitioned between water and EtOAc and the organic fraction was then washed with brine, then dried over sodium sulfate and concentrated onto silica gel and purified by chromatography (gradient: 9:1 hexanes:EtOAc to EtOAc) delivering both the product 90 mg, 23% yield). MS (ES+) m/z 707.9 (M+Na) and m/z 807.9 (M+Na+Boc) and doubly Boc-protected material.

Aufarbeitung

  1. customThe mixture was degassed with nitrogen
  2. customThe mixture was degassed again
  3. customThe crude mixture was partitioned between water and EtOAc
  4. washthe organic fraction was then washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated onto silica gel
  7. custompurified by chromatography (gradient: 9:1 hexanes:EtOAc to EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-e11eea1f02e54f36823039e21745c3a7
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08604023B2

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