反应详情

温度

65 °C

4-Morpholin-4-ylmethyl-benzene-1,2-diamine (1 mol. eq.) and 4-nitro-1H-pyrazole-3-carboxylic acid (1 mol. eq.) were dissolved in dimethylformamide (DMF) (10 vol.). O-(Benzot πazol-1-yl)-N,N,N′,N1-tetramethyluronium tetrafluoroborate (TBTU) (1.2 mol. eq.) was added and the mixture was stiffed at ambient temperature for 24 hours. The mixture was concentrated in vacuo until no further solvent was seen to distil. The residue was then dissolved in glacial acetic acid (10 vol.) and heated at 65° C. for ˜12 hours. The mixture was concentrated in vacuo and then dissolved in water (6 vol.) at 75° C. The black solution was cooled to 0-5° C. over 2 hours during which time a solid was formed. The solid was removed by filtration and the aqueous filtrate was diluted with ethyl acetate (4 vol.) and tetrahydrofuran (2 vol.). Solid NaHCO3 was added slowly to the stirred mixture until no further effervescence was observed and a pII of 6.8 was reached. The mixture was then stirred until a precipitation was observed. After standing the mixture at 0-5° C. for 2 hours, the solid was collected by filtration and washed with water (2 vol.) and ethyl acetate (2 vol.) and dried to give 5-morpholin-4-ylmethyl-2-(4-nitro-1H-pyrazol-3-yl)1H-benzimidazole as a brown solid (40%). (LC/MS (basic method): Rt 1.93, [M−H+]− 327).

1. concentrationThe mixture was concentrated in vacuo until no further solvent
2. customto distil
3. dissolutionThe residue was then dissolved in glacial acetic acid (10 vol.)
4. concentrationThe mixture was concentrated in vacuo
5. dissolutiondissolved in water (6 vol.) at 75° C
6. temperatureThe black solution was cooled to 0-5° C. over 2 hours during which time a solid
7. customwas formed
8. customThe solid was removed by filtration
9. additionthe aqueous filtrate was diluted with ethyl acetate (4 vol.) and tetrahydrofuran (2 vol.)
10. additionSolid NaHCO3 was added slowly to the stirred mixture until no further effervescence
11. customat 0-5° C.
12. customfor 2 hours
13. filtrationthe solid was collected by filtration
14. washwashed with water (2 vol.) and ethyl acetate (2 vol.)
15. customdried