Reaktion #2269559

Reaktionsgleichung

3-(5-ethyl-6-methyl-1H-benzoimidazol-2-yl)-1H-indazole-5-carbonitrile

hydrochloric acid

sodium carbonate

→

3-(5-ethyl-6-methyl-1H-benzoimidazol-2-yl)-1H-indazole-5-carboxylic acid amide dihydrochloride

Lösungsmittel

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction was cooled to ambient temperature
2. 2
   TemperaturThe reaction was then heated at 80° C. for 2.5 hours
3. 3
   workup.WAITat 100° C. for 2 hours
4. 4
   FiltrationThe resulting white precipitate was collected by filtration
5. 5
   Extraktionthe aqueous layer was extracted with ethyl acetate
6. 6
   Einengenconcentrated in vacuo
7. 7
   workup.ADDITIONcontaining MP-carbonate resin (100 mg)
8. 8
   workup.STIRRINGshaken for 16 hours
9. 9
   FiltrationThe reaction was then filtered
10. 10
    Waschenthe resin washed with methanol
11. 11
    Einengenthe combined organic layers concentrated in vacuo
12. 12
    SonstigeThe residue was triturated with diethyl ether
13. 13
    SonstigeThe solvent was removed in vacuo

Vorschrift

A stirred suspension of 3-(5-ethyl-6-methyl-1H-benzoimidazol-2-yl)-1H-indazole-5-carbonitrile [100 mg, Example 235(an)] in acetic acid (1 ml) and concentrated hydrochloric acid (1 ml) was heated at 80° C. for 30 minutes and then at 100° C. for 4 hours. The reaction was cooled to ambient temperature and stirred for 16 hours. The reaction was then heated at 80° C. for 2.5 hours and then at 100° C. for 2 hours. The reaction mixture was cooled to ambient temperature and neutralized with aqueous sodium carbonate solution. The resulting white precipitate was collected by filtration and the aqueous layer was extracted with ethyl acetate, combined with the precipitate and concentrated in vacuo. The residue was taken up in methanol, transferred to a solid phase cartridge containing MP-carbonate resin (100 mg) and shaken for 16 hours. The reaction was then filtered, the resin washed with methanol and the combined organic layers concentrated in vacuo. The residue was triturated with diethyl ether, taken up in methanol and acidified with 4M hydrogen chloride in 1,4-dioxane. The solvent was removed in vacuo to give 3-(5-ethyl-6-methyl-1H-benzoimidazol-2-yl)-1H-indazole-5-carboxylic acid amide dihydrochloride (58 mg) as a pale brown solid. LC-MS (METHOD M): RT=9.40 minutes, 320(M+H)+.

Quelle