Reaktion #972203

Reaktionsgleichung

cesium hydroxide monohydrate

(E)-5,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

2-oxo-2,3-dihydro-1H-benzoimidazole-5-boronic acid pinacol ester

lithium chloride

→

(Z)-7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-5-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one

Lösungsmittel

water

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeNitrogen was bubbled into the solution as reagents
2. 2
   workup.ADDITIONwere added
3. 3
   SonstigeAfter bubbling nitrogen through the mixture for 5 minutes it
4. 4
   TemperaturFollowing heating for 2 hours
5. 5
   Temperaturthe mixture was cooled to ambient temperature
6. 6
   workup.ADDITIONdiluted with ethyl acetate (50 mL)
7. 7
   Waschenwashed with water (2×40 mL)
8. 8
   Trocknenbrine (40 mL), dried with sodium sulfate
9. 9
   Sonstigedecanted
10. 10
    Einengenconcentrated in the presence of silica
11. 11
    Wascheneluted with a gradient of 0-100% ethyl acetate in hexanes

Vorschrift

(E)-5,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.68 g, 1.44 mmol), 2-oxo-2,3-dihydro-1H-benzoimidazole-5-boronic acid pinacol ester (0.37 g, 1.44 mmol) and lithium chloride (0.183 g, 4.31 mmol) were added to 1,4-dioxane (12 mL). Nitrogen was bubbled into the solution as reagents were added. Tetrakis(triphenylphosphine) palladium(0) (166 mg, 0.144 mmol) was added followed by cesium hydroxide monohydrate (723 mg, 4.31 mmol) and water (1 mL). After bubbling nitrogen through the mixture for 5 minutes it was heated to 100° C. under a nitrogen atmosphere. Following heating for 2 hours, the mixture was cooled to ambient temperature, diluted with ethyl acetate (50 mL), washed with water (2×40 mL), then brine (40 mL), dried with sodium sulfate, decanted, then concentrated in the presence of silica. The resulting silica gel-bound crude product was loaded onto a silica gel column and eluted with a gradient of 0-100% ethyl acetate in hexanes to yield (Z)-7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-5-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one as a 2:1 mixture of product:2-oxo-2,3-dihydro-1H-benzoimidazole-5-boronic acid pinacol ester (200 mg, 24%). ESI m/z 571.1, 573.1.

Quelle