3-(2-methyl-5-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione → Avadomide

HRID 1409614Notes

Reaction equation

HRID 1409614 reaction equation
[CH3:1][C:2]1[N:11]([CH:12]2[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]2=[O:19])[C:10](=[O:20])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[N+:21]([O-])=O)[N:3]=1>CN(C=O)C.[OH-].[OH-].[Pd+2]>[NH2:21][C:8]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:9]=1[C:10](=[O:20])[N:11]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:2]([CH3:1])=[N:3]2

Participants

4

Reactant 1

HCID 666429823-(2-methyl-5-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione

Product 1

HCID 24967599AvadomideYield 69%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(2-methyl-5-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (250 mg) and Pd(OH)2 on carbon (110 mg) in DMF (40 mL) was shaken under hydrogen (50 psi) for 12 hours. The suspension was filtered through a pad of Celite and washed with DMF (10 mL). The filtrate was concentrated in vacuo and the resulting oil was purified by flash column chromatography (silica gel, methanol/methylene chloride) to give 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (156 mg, 69% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, 3.52 min (99.9%); mp: 293-295° C.; 1H NMR (DMSO-d6) δ 2.10-2.17 (m, 1H, CHH), 2.53 (s, 3H, CH3), 2.59-2.69 (m, 2H, CH2), 2.76-2.89 (m, 1H, CHH), 5.14 (dd, J=6, 11 Hz, 1H, NCH), 6.56 (d, J=8 Hz, 1H, Ar), 6.59 (d, J=8 Hz, 1H, Ar), 7.02 (s, 2H, NH2), 7.36 (t, J=8 Hz, 1H, Ar), 10.98 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.98, 23.14, 30.52, 55.92, 104.15, 110.48, 111.37, 134.92, 148.17, 150.55, 153.62, 162.59, 169.65, 172.57; LCMS: MH=287; Anal. Calcd. for C14H14N4O3+0.3H2O: C, 57.65; H, 5.05; N, 19.21. Found: C, 57.50; H, 4.73; N, 19.00.

Workup

  1. filtrationThe suspension was filtered through a pad of Celite
  2. washwashed with DMF (10 mL)
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe resulting oil was purified by flash column chromatography (silica gel, methanol/methylene chloride)

Sources & evidence

ORD record
ord-2b19ca7ebd1c452b9a1d8a1c966bf583
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

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