Triethylamine → 3-Amino-5-methoxy-1-(2,2,3,3,7-pentafluoro-2,3-dihydro-1,4-benzodioxin-6-yl)pyridazin-4(1H)-one

HRID 1895175Notes

Reaction equation

[CH3:1][O:2][C:3]1[C:4](=[O:27])[C:5](C(O)=O)=[N:6][N:7]([C:9]2[C:22]([F:23])=[CH:21][C:12]3[O:13][C:14]([F:20])([F:19])[C:15]([F:18])([F:17])[O:16][C:11]=3[CH:10]=2)[CH:8]=1.C1C=CC(P([N:42]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.CCN(CC)CC.[OH-].[Na+]>C1(C)C=CC=CC=1>[NH2:42][C:5]1[C:4](=[O:27])[C:3]([O:2][CH3:1])=[CH:8][N:7]([C:9]2[C:22]([F:23])=[CH:21][C:12]3[O:13][C:14]([F:20])([F:19])[C:15]([F:18])([F:17])[O:16][C:11]=3[CH:10]=2)[N:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 5-methoxy-4-oxo-1-(2,2,3,3,7-pentafluoro-2,3-dihydro-1,4-benzodioxin-6-yl)-1,4-dihydropyridazine-3-carboxylic acid (2.33 g, 5.91 mmol), DPPA (1.90 mL, 8.86 mmol) and Et3N (1.23 mL, 8.86 mmol) in toluene (23 mL) was heated to 100° C. for 90 min. To the mixture was added 8 M NaOH aqueous solution (7.4 mL) at 0° C. The mixture was stirred at room temperature for 2 h, extracted with EtOAc, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on basic silica gel (hexane/EtOAc=50/50 to 0/100) and on silica gel (hexane/EtOAc=80/20 to 0/100) and triturated with EtOAc/hexane to yield the title compound (1.12 g, 53% yield) as a white solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.73 (3H, s), 6.24 (2H, s), 7.92 (1H, d, J=10.5 Hz), 7.99 (1H, d, J=6.8 Hz), 8.37 (1H, d, J=1.5 Hz).

Workup

extractionextracted with EtOAc
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
custompurified by column chromatography on basic silica gel (hexane/EtOAc=50/50 to 0/100) and on silica gel (hexane/EtOAc=80/20 to 0/100)
customtriturated with EtOAc/hexane

Sources & evidence

ORD record: ord-a86dd00f2c324fd19bd2d64744f271c5
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513251B2

Reaction notes

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