Water → 5-bromo-6-(methylsulfamoyl)-N-acetylindoline
Reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([Br:17])=[C:10]([S:13](Cl)(=[O:15])=[O:14])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH2:18]([N:20](CC)CC)C.CN.O>C1COCC1>[CH3:18][NH:20][S:13]([C:10]1[CH:11]=[C:12]2[C:7]([CH2:6][CH2:5][N:4]2[C:1](=[O:3])[CH3:2])=[CH:8][C:9]=1[Br:17])(=[O:15])=[O:14]Participants
Procedure
To a slurry of 1-acetyl-5-bromo-2,3-dihydro-1H-indole-6-sulfonyl chloride (see Preparation 43) (0.40 g, 1.2 mmol) in THF (3.38 mL) was added triethylamine (0.660 mL, 4.73 mmol) and 40% methylamine in water (0.18 mL, 2.4 mmol). The reaction was heated to reflux and stirred for 1.5 h, then cooled and concentrated. The residue was slurried in hot MeOH and filtered under vacuum washing with MeOH. The solid was dried in vacuo at 40° C., to give 1-acetyl-5-bromo-2,3-dihydro-1H-indole-6-sulfonic acid methylamide (0.33 g, 85%) as a colourless solid. This product (320 mg, 1.0 mmol) was slurried in 1,4-dioxane (0.98 mL) and concentrated hydrochloric acid (0.72 mL), heated to 100° C. for 1.5 h, then cooled to ambient temperature solvent removed in vacuo. The pH was adjusted to 7 with 1 M aqueous NaOH and the resulting precipitate collected by vacuum filtration, washed with water and dried in vacuo at 40° C., to give the title compound (0.176 g, 62%) as a beige solid; MS: [M+H]+ 291
Workup
- temperatureThe reaction was heated
- temperatureto reflux
- temperaturecooled
- concentrationconcentrated
- filtrationfiltered under vacuum
- washwashing with MeOH
- customThe solid was dried in vacuo at 40° C.
Sources & evidence
- ORD record
- ord-9643ed9876414c18abdf7544a6c80c57
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09018214B2
Reaction notes
Loading…