Dimethylamine, hydrochloride → 9-Bromo-4-dimethylamino-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester

HRID 575104Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[CH:8](Br)[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4].Cl.[CH3:22][NH:23][CH3:24].CCN(C(C)C)C(C)C>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[CH:8]([N:23]([CH3:24])[CH3:22])[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 4,9-Dibromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (200 mg, 0.477 mmol) in THF (6 mL) were added Dimethylamine Hydrochloride (77.8 mg, 0.954 mmol), DIPEA (308 mg, 2.38 mmol). The reaction mixture was stirred in autoclave at 60° C. overnight. Then the mixture was cooled to room temperature and partitioned between EtOAc and H2O, and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo and purified by flash column chromatography (silica gel, EtOAc in hexane from 10% to 20%) to afford 9-Bromo-4-dimethylamino-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (120 mg, 65%).

Workup

temperatureThen the mixture was cooled to room temperature
custompartitioned between EtOAc and H2O
extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
custompurified by flash column chromatography (silica gel, EtOAc in hexane from 10% to 20%)

Sources & evidence

ORD record: ord-c1abf5dcdd764057b468db170e5258dc
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034866B2

Reaction notes

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