Hydrochloric Acid → Ethyl 6-difluoromethoxy-3-ethyl-4-oxo-3,4-dihydrobenzo[4,5]furo[2,3-d]pyridazine-9-carboxylate

HRID 1091872Notes

Reaction equation

[F:1][CH:2]([F:23])[O:3][C:4]1[C:9]2[O:10][C:11]3[C:12](=[O:17])[NH:13][N:14]=[CH:15][C:16]=3[C:8]=2[C:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:6][CH:5]=1.[H-].[Na+].[CH2:26](Br)[CH3:27].Cl>CN(C=O)C.O>[F:23][CH:2]([F:1])[O:3][C:4]1[C:9]2[O:10][C:11]3[C:12](=[O:17])[N:13]([CH2:26][CH3:27])[N:14]=[CH:15][C:16]=3[C:8]=2[C:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 5 °C

Procedure

To a solution of ethyl 6-difluoromethoxy-4-oxo-3,4-dihydrobenzo[4,5]furo[2,3-d]pyridazine-9-carboxylate (from step 6 of example 4) (261 mg, 0.803 mmol) in n,n-dimethyl formamide, sodium hydride (33 mg, 0.803 mmol) was added at 20-30° C. under nitrogen. Ethyl bromide (95.4 mg, 0.88 mmol) was added to the reaction mixture. Progress of reaction was monitored by TLC. At the end, reaction mixture was cooled to 0-10° C. Water (100 ml) was added dropwise to the reaction mixture at 0-10° C. and acidified with dilute hydrochloric acid. The precipitate obtained was filtered and dried in oven. It was purified by silica gel column chromatography using 10% ethyl acetate in chloroform. White colored solid (130 mg) was obtained.

Workup

customProgress of reaction
customAt the end, reaction mixture
customThe precipitate obtained
filtrationwas filtered
customdried in oven
customIt was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-9ce522294ec94ae2bab75e339a3dedf5
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129401B2

Reaction notes

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