Thionyl Chloride → N-[5-(3,5-difluoro-benzyloxy)-1H-indazol-3-yl]-4-[(3-dimethylamino-propyl)-methyl-amino]-2-nitro-benzamide

Temperature

4 °C

4-[(3-Dimethylamino-propyl)-methyl-amino]-2-nitro-benzoic acid hydrochloride (500 mg, 1.57 mmol) in dry THF (15 mL) was treated with one drop of DMF and with neat SOCl2 (0.34 mL, 4.69 mmol). The reaction mixture was refluxed for 0.5 hours, evaporated. The residue was taken in toluene (10 mL) and evaporated to dryness to afford a yellow solid that was suspended in dry pyridine (15 mL), cooled to 4° C. and treated with 5-(3,5-difluoro-benzyloxy)-1H-indazol-3-ylamine (360 mg, 1.31 mmol) in pyridine (5 mL). The solution was left at 4° C. over night and evaporated. The residue was dissolved in DCM (250 mL), washed with saturated NaHCO3 solution, water and brine. After drying over sodium sulfate and removal of the solvent, the crude was purified over silica gel (DCM: NH3 7N in MeOH 93:7) to afford 45 mg of title compound as an amorphous yellow solid (yield: 64%).

1. temperatureThe reaction mixture was refluxed for 0.5 hours
2. customevaporated
3. customevaporated to dryness
4. customto afford a yellow solid
5. waitThe solution was left at 4° C. over night
6. customevaporated
7. dissolutionThe residue was dissolved in DCM (250 mL)
8. washwashed with saturated NaHCO3 solution, water and brine
9. dry with materialAfter drying over sodium sulfate and removal of the solvent
10. customthe crude was purified over silica gel (DCM: NH3 7N in MeOH 93:7)

ORD record

ord-3c5540498d094a5dbba431a1a1eeb14c

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354399B2