Hydrochloric Acid → N-{[5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine

HRID 2046301Notes

Reaction equation

[OH:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[N:6][NH:5][C:4](=[O:11])[C:3]=1[C:12]([O:14]CC)=O.[Na+].[NH2:18][CH2:19][C:20]([O-:22])=[O:21].Cl>COCCO.O>[OH:1][C:2]1[C:7]([CH:8]([CH3:9])[CH3:10])=[N:6][NH:5][C:4](=[O:11])[C:3]=1[C:12]([NH:18][CH2:19][C:20]([OH:22])=[O:21])=[O:14]

Participants

Conditions

Temperature: 130 °C

Procedure

To a 100 mL round bottom flask was added ethyl 5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinecarboxylate (example 14(a), 55 mg, 0.243 mmol) and Glycine Sodium Salt (59.0 mg, 0.608 mmol) in 2-methoxyethanol (10 ml) and the mixture was refluxed at 130° C. for 2 hours. The mixture was diluted with water (10 ml) and acidified with 1N HCl. The aqueous solution was then extracted with ethyl acetate (40 mL), organics dried over MgSO4, filtered and solvents removed by evaporation. The crude oil was purified by HPLC chromatography (ODS silica, gradient 25-95% acetonitrile/water (0.1% TFA)) to afford the title compound, N-{[5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (45 mg, 0.175 mmol, 71.8% yield), as a white solid. 1H NMR (400 MHz, DMSO-d6) d ppm 15.74 (br. s., 1H), 13.07 (s, 1H), 10.19 (t, J=5.68 Hz, 1H), 4.11 (d, J=5.81 Hz, 2H), 3.14 (sept, J=6.82 Hz, 1H), 1.17 (d, J=6.82 Hz, 6H). MS (ES+) m/e 256 [M+H]+.

Workup

extractionThe aqueous solution was then extracted with ethyl acetate (40 mL)
dry with materialorganics dried over MgSO4
filtrationfiltered
customsolvents removed by evaporation
customThe crude oil was purified by HPLC chromatography (ODS silica, gradient 25-95% acetonitrile/water (0.1% TFA))

Sources & evidence

ORD record: ord-856edd2869df4d8ea1d1707ba6671b48
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: USRE044613E1

Reaction notes

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