Reaktion #972202

Reaktionsgleichung

cesium hydroxide monohydrate

(E)-3-(2-Bromobenzyl)-5,7-dichloro-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one

5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2(3H)-one

lithium chloride

→

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

Ausbeute 19.0%

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 for 5 minutes
4. 4
   TemperaturAfter heating for 1 hour
5. 5
   Temperaturthe mixture was cooled to ambient temperature
6. 6
   workup.ADDITIONdiluted with ethyl acetate (25 mL)
7. 7
   Waschenwashed with water (2×20 mL)
8. 8
   Trocknenbrine (20 mL), dried with sodium sulfate
9. 9
   Sonstigedecanted
10. 10
    Einengenthen concentrated in the presence of silica
11. 11
    SonstigeThe dried silica-bound residue was dry
12. 12
    Wascheneluted with a gradient of 60-100% ethyl acetate in hexanes

Vorschrift

(E)-3-(2-Bromobenzyl)-5,7-dichloro-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one (150 mg, 0.364 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2(3H)-one (95 mg, 0.364 mmol) and lithium chloride (46 mg, 1.09 mmol) were added to 1,4-dioxane (3 mL). Nitrogen was bubbled into the solution as reagents were added. Tetrakis(triphenylphosphine) palladium(0) (42 mg, 0.036 mmol) was added followed by cesium hydroxide monohydrate (183 mg, 1.09 mmol) and water (1 mL). After bubbling nitrogen through for 5 minutes, the reaction mixture was heated to 100° C. under a nitrogen atmosphere. After heating for 1 hour, the mixture was cooled to ambient temperature, diluted with ethyl acetate (25 mL), washed with water (2×20 mL), then brine (20 mL), dried with sodium sulfate, decanted then concentrated in the presence of silica. The dried silica-bound residue was dry loaded onto a silica gel column and eluted with a gradient of 60-100% ethyl acetate in hexanes then a gradient of 0-25% methanol in ethyl acetate to yield (Z)-3-(2-bromobenzyl)-7-chloro-1-methyl-5-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one (35 mg, 19%). 1H NMR (300 MHz, DMSO-d6) δ 3.32 (s, 3H) 3.49 (m, 2H), 3.82 (t, 1H), 6.89-7.17 (m, 3H), 7.28-7.71 (m, 7H), 10.70 (s, 1H), 10.87 (s, 1H); ESI m/z measured 509.0359 [M+H]+, calculated 509.0380.

Quelle