Trifluoroacetic acid → 6-Bromo-N'-(4-morpholinylacetyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-4-carbohydrazide

Temperature

50 °C

6-Bromo-N′-(4-morpholinylacetyl)-1H-indazole-4-carbohydrazide (0.232 g, 0.607 mmol) in ethyl acetate (3 ml) was treated with 3,4-dihydro-2H-pyran (0.111 ml, 1.214 mmol) then heated to 50° C. under nitrogen. Trifluoroacetic acid (4 drops) was added and heating continued for 1.5 h at 50° C. A further portion of 3,4-dihydro-2H-pyran (0.111 ml, 1.214 mmol) and trifluoroacetic acid (0.047 ml, 0.607 mmol) were added and heating continued for a further 1.5 h. The solution was left to stand at room temperature for 18 h. The clear solution was diluted with ethyl acetate (5 ml), washed with saturated aqueous sodium bicarbonate (2×10 ml), filtered through a phase separator cartridge then blown to dryness and left under vacuum. The crude product was dissolved in dichloromethane (2 ml) and purified on a silica (5 g) cartridge which was eluted with a gradient of methanol and chloroform and the appropriate fractions evaporated to give the title compound as a beige gummy solid (0.199 g).

1. temperatureheating
2. temperatureheating
3. waitcontinued for a further 1.5 h
4. waitThe solution was left
5. waitto stand at room temperature for 18 h
6. washwashed with saturated aqueous sodium bicarbonate (2×10 ml)
7. filtrationfiltered through a phase separator cartridge
8. waitleft under vacuum
9. dissolutionThe crude product was dissolved in dichloromethane (2 ml)
10. custompurified on a silica (5 g) cartridge which
11. washwas eluted with a gradient of methanol and chloroform
12. customthe appropriate fractions evaporated

ORD record

ord-aa1dc81e496846f19a3c3ae2aefe75dc

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08524751B2