Acetone → N-{[5-Hydroxy-6-(1-methylethyl)-3-oxo-2-(phenylmethyl)-2,3-dihydro-4-pyridazinyl]carbonyl}glycine

Ethyl 3-oxo-3-[1-(phenylmethyl)hydrazino]propanoate. A mixture of benzylhydrazine dihydrochloride (2.50 g, 12.8 mmol), potassium carbonate (1.77 g, 12.8 mmol), acetone (6.0 mL, 82 mmol) and ethyl acetate (30 mL) was stirred at room temperature while a solution of 1M aqueous sodium hydroxide (6.0 mL, 6.0 mmol) was added dropwise. After the addition, the mixture was stirred 0.5 h, then excess magnesium sulfate added and the mixture filtered. The filtrate was evaporated under reduced pressure and the residue azeotroped with toluene three times, then dissolved in tetrahydrofuran (50 mL). 1,8-Diazabicyclo[5.4.0]undec-7-ene (1.84 mL, 12.3 mmol) was added to the stirred solution under nitrogen at 0° C., followed by ethyl 3-chloro-3-oxopropionate (1.57 mL, 12.3 mmol) dropwise. The mixture was stirred at 0° C. for 5 min, and at room temperature for 3 h, then 1M aqueous hydrochloric acid (50 mL) added. After stirring a further 0.5 h, water (100 mL) was added and the mixture extracted with ethyl acetate. The extracts were washed with brine, dried (MgSO4), evaporated under reduced pressure and the residue chromatographed (silica gel, 1-5% methanol/dichloromethane) to give the title compound (1.60 g) as an oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.18 (t, J=7.08 Hz, 3H) 3.56 (s, 2H) 4.08 (q, J=7.16 Hz, 2H) 4.58 (s, 2H) 4.65 (s, 2H) 7.25-7.36 (m, 5H).

1. additionwas added dropwise
2. additionAfter the addition
3. filtrationthe mixture filtered
4. customThe filtrate was evaporated under reduced pressure
5. customthe residue azeotroped with toluene three times
6. dissolutiondissolved in tetrahydrofuran (50 mL)
7. stirringThe mixture was stirred at 0° C. for 5 min
8. waitat room temperature for 3 h
9. stirringAfter stirring a further 0.5 h
10. extractionthe mixture extracted with ethyl acetate
11. washThe extracts were washed with brine
12. dry with materialdried (MgSO4)
13. customevaporated under reduced pressure
14. customthe residue chromatographed (silica gel, 1-5% methanol/dichloromethane)

ORD record

ord-793038f7ad86481a8ec5c483d0d67e68

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07608621B2