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

HRID 1868222Notes

Reaction equation

HRID 1868222 reaction equation
[NH2:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[C:3]=1[C:4]([NH:6][CH:7]1[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]1=[O:14])=[O:5].[CH:20](OC)(OC)OC.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C(#N)C.CCOCC>[CH3:19][C:15]1[CH:16]=[CH:17][CH:18]=[C:2]2[C:3]=1[C:4](=[O:5])[N:6]([CH:7]1[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]1=[O:14])[CH:20]=[N:1]2

Participants

7

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 659566542-amino-N-(2,6-dioxo-piperidin-3-yl)-6-methyl-benzamide

Product 1

HCID 247622423-(5-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dioneYield 47%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-6-methyl-benzamide (0.60 g, 2.2 mmol), trimethyl orthoformate (3 mL, 26.8 mmol), and p-toluene sulfonic acid (0.060 g) in acetonitrile (20 mL) was heated to reflux for 30 hours. The mixture was cooled to room temperature. To the mixture, water (75 mL) and ether (20 mL) were added, and the resulting mixture was stirred for 2 hours. The suspension was filtered and washed with water and ether (50 mL each) to give 3-(5-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (0.28 g, 47% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 3.08 min (99%); mp: 262-264° C.; 1H NMR (DMSO-d6) δ 2.09-2.16 (m, 1H, CHH), 2.62-2.84 (m, 6H, CH2, CH3, CHH), 5.42 (brs, 1H, NCH), 7.32 (d, J=7 Hz, 1H, Ar), 7.52 (d, J=8 Hz, 1H, Ar), 7.69 (t, J=8 Hz, 1H, Ar), 8.30 (s, 1H, CH), 11.12 (s, 1H, NH); 13C NMR (DMSO-d6) δ22.35, 22.62, 30.88, 58.00, 119.81, 125.36, 129.57, 133.72, 140.15, 147.08, 149.07, 160.21, 169.91, 172.33, 172.44; LCMS: MH=272; Anal. Calcd. for C14H13N3O3: C, 61.99; H, 4.83; N, 15.49. Found: C, 61.67; H, 4.40; N, 15.41.

Workup

  1. temperatureto reflux for 30 hours
  2. filtrationThe suspension was filtered
  3. washwashed with water and ether (50 mL each)

Sources & evidence

ORD record
ord-37ab9e05b19a45d7b4c06d95a70f941c
Source dataset
uspto-grants-2009_12
Patent number
US07635700B2

Reaction notes

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