p-Toluenesulfonic acid → 3-(5-chloro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione

HRID 1868230Notes

Reaction equation

HRID 1868230 reaction equation
[NH2:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl: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>CO>[Cl: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

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 659566532-amino-N-(2,6-dioxo-piperidin-3-yl)-6-chloro-benzamide

Product 1

HCID 249675943-(5-chloro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dioneYield 48%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-6-chloro-benzamide (0.8 g, 2.8 mmol) and trimethyl orthoformate (4 mL) and p-toluene sulfonic acid (280 mg) was heated to 150° C. via a microwave oven for 30 minutes. To the mixture, was added methanol (15 mL), and the mixture was stirred for 5 minutes. The suspension was filtered and washed with methanol to give 3-(5-chloro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (400 mg, 48% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 2.35 min (99.2%); mp: 308-310° C.; 1H NMR (DMSO-d6) δ 2.13-2.19 (m, 1H, CHH), 2.57-2.72 (m, 2H, 2CHH), 2.83-2.89 (m, 1H, CHH), 5.43 (br, 1H, NCH), 7.60 (dd, J=1, 8 Hz, 1H, Ar), 7.66 (dd, J=1, 8 Hz, 1H, Ar), 7.79 (t, J=8 Hz, 1H, Ar), 8.39 (s, 1H, CH), 11.16 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.18, 30.84, 56.16, 118.35, 126.81, 129.74, 132.45, 134.54, 148.18, 149.98, 157.62, 169.68, 172.39; LCMS: MH=292, 294; Anal Calcd for C13H10N3O3Cl+0.15H2O: C, 53.04; H, 3.53; N, 14.27. Found: C, 52.68; H, 3.14; N, 14.17.

Workup

  1. filtrationThe suspension was filtered
  2. washwashed with methanol

Sources & evidence

ORD record
ord-d213e97bb6b3404687cf0d9477ac6c8c
Source dataset
uspto-grants-2009_12
Patent number
US07635700B2

Reaction notes

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