Acetic Acid → N-Methylated pomalidomide

HRID 718718Notes

Reaction equation

HRID 718718 reaction equation
[CH3:1]C([O-])(C)C.[Na+].[CH:7]1[CH:8]=[C:9]2[C:17](=[O:18])[N:16]([CH:19]3[C:25](=[O:26])[NH:24][C:22](=[O:23])[CH2:21][CH2:20]3)[C:14](=[O:15])[C:10]2=[C:11]([NH2:13])[CH:12]=1.CI.C(O)(=O)C>CS(C)=O>[NH2:13][C:11]1[CH:12]=[CH:7][CH:8]=[C:9]2[C:10]=1[C:14](=[O:15])[N:16]([CH:19]1[CH2:20][CH2:21][C:22](=[O:23])[N:24]([CH3:1])[C:25]1=[O:26])[C:17]2=[O:18]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6328Methyl iodideHCID 134780PomalidomideHCID 23676156Sodium t-butoxide

Product 1

HCID 58572149N-Methylated pomalidomideYield 19%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a solution of NaOtBu (0.074 g, 0.769 mmol) in DMSO (0.8 mL) was added a solution of pomalidomide (0.100 g, 0.366 mmol) in DMSO (0.5 mL plus 0.5 mL rinse) dropwise. The reaction was stirred for 10 min at room temperature followed by the addition of methyl iodide (0.025 mL, 0.403 mmol). After 18 h, glacial acetic acid (0.1 mL) was added to the reaction volatiles were removed in vacuo, and the crude dark-brown residue was purified by preparative reverse phase HPLC to afford 29 (0.02 g, 19%) as light yellow powder. 1H NMR (400 MHz, DMSO) δ 7.46 (dd, J=8.4, 7.0 Hz, 1H), 7.00 (dd, J=7.6, 5.6 Hz, 2H), 6.53 (br s, 2H), 5.11 (dd, J=13.2, 5.7 Hz, 1H), 2.97-2.83 (m, 1H), 2.76 (s, 1H), 2.57-2.51 (m, 1H), 2.06-1.91 (m, 1H). MS (ESI) m/z calcd for C14H14N3O4[M+H]+ 288.3, found: 288.5.

Workup

  1. waitAfter 18 h
  2. customwere removed in vacuo
  3. customthe crude dark-brown residue was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-aef1631f2fb14dbca758c73910ddc223
Source dataset
uspto-grants-2015_11
Patent number
US09193989B2

Reaction notes

Loading…