Sodium Dithionite → 1-(4-amino-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea

HRID 1091321

Reaction equation

[O:1]=[C:2]1[CH:7]([N:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([CH2:17][NH:18][C:19]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([N+:28]([O-])=O)=[CH:24][CH:23]=4)=[O:20])[CH:14]=3)[C:9]2=[O:31])[CH2:6][CH2:5][C:4](=[O:32])[NH:3]1.S(S([O-])=O)([O-])=O.[Na+].[Na+]>CCO.O>[NH2:28][C:25]1[CH:26]=[CH:27][C:22]([NH:21][C:19]([NH:18][CH2:17][C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[C:9](=[O:31])[N:8]([CH:7]2[CH2:6][CH2:5][C:4](=[O:32])[NH:3][C:2]2=[O:1])[CH2:16]3)=[O:20])=[CH:23][CH:24]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred mixture of 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-3-(4-nitrophenyl)urea (150 mg, 0.343 mmol) in EtOH (2 mL) was added sodium dithionite (597 mg, 3.43 mmol) in water (2 mL). The resulting mixture was heated to 60° C. for 20 min at which time LC-MS indicated complete disappearance of nitro starting material. The reaction mixture was combined with the crude product from a separate run and concentrated in mew). The residue was dissolved in minimal DMF and chromatographed on a C-18 preparative HPLC column equipped with mass triggered collection. The desired fractions were combined and concentrated in vacuo to provide 1-(4-amino-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea as a pale yellow solid (90 mg, 40% combined average yield from two separate runs): mp: >400° C.; LCMS: MH+=408.

Workup

concentrationconcentrated in mew)
dissolutionThe residue was dissolved in minimal DMF
customchromatographed on a C-18 preparative HPLC column
customequipped with mass
customcollection
concentrationconcentrated in vacuo
customto provide

Sources & evidence

ORD record: ord-55ae4c0425ae442088de6718a92a1c28
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129375B2

Linked notes

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