Hydrochloric Acid → HCID 70982683, compound

HRID 2201759Notes

Reaction equation

[CH2:1]([CH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:18][CH2:19][NH:20][S:21]([C:24]3[N:25]=[CH:26][N:27]([CH3:29])[CH:28]=3)(=[O:23])=[O:22])[CH:15]=2)[C:10](=O)[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CSC.B.Cl.[OH-].[Na+]>C1COCC1>[CH2:1]([CH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:18][CH2:19][NH:20][S:21]([C:24]3[N:25]=[CH:26][N:27]([CH3:29])[CH:28]=3)(=[O:23])=[O:22])[CH:15]=2)[CH2:10][NH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of N-(2-(3-benzyl-1-oxoisoindolin-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide (example 1.7, 111 mg, 0.26 mmol) in dry THF (1.6 mL) was added borane dimethyl sulfide complex (0.78 mL, 1.56 mmol, 2M in THF) under N2. The reaction mixture was heated up to 65° C. for 7 hours, then stirred at room temperature for overnight. Quenched reaction by carefully addition of 0.5 N HCl (0.5 mL) solution and the mixture was refluxed for 2 hours, then basified the reaction mixture with 1N NaOH aqueous to pH=8-9, extracted 2× with ethyl acetate, this was separated. The organic phase was dried on Na2SO4 and the solvent was evaporated. The residue was purified by flash-chromatography on silica gel with 5-10% MeOH in DCM (0.5% NEt3 added), 22.2 mg (21%) of the product was obtained.

Workup

customQuenched
customreaction
temperaturethe mixture was refluxed for 2 hours
extractionextracted 2× with ethyl acetate
customthis was separated
customThe organic phase was dried on Na2SO4
customthe solvent was evaporated
customThe residue was purified by flash-chromatography on silica gel with 5-10% MeOH in DCM (0.5% NEt3 added)

Sources & evidence

ORD record: ord-8665564ae5f54353b784006dbe5ede75
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365512B2

Reaction notes

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