반응 #540193

반응 방정식

2-amino-N-(2,6-dioxo-piperidin-3-yl)-5-methyl-benzamide

trimethyl orthoformate

p-toluene sulfonic acid

methanol

→

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

수율 9.0%

용매

methylene chloride

반응 조건

후처리

1. 1
   기타The solvent was removed in vacuo
2. 2
   기타was purified with column chromatography (Silca Gel, methanol/methylene chloride 0% gradient 10% in 15 min)

실험 절차

A solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-5-methyl-benzamide (0.45 g, 1.7 mmol) and trimethyl orthoformate (4 mL) and p-toluene sulfonic acid (80 mg) was heated to 160° C. in a microwave oven for 8 minutes. To the suspension, was added methanol (20 mL), methylene chloride (20 mL), and Celite (5 mL). The solvent was removed in vacuo. The reside was placed in a SIM and was purified with column chromatography (Silca Gel, methanol/methylene chloride 0% gradient 10% in 15 min) to give as 3-(6-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a blue solid (50 mg, 9% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 2.78 min (96.1%); mp: 285-287° C.; 1H NMR (DMSO-d6) δ 2.11-2.18 (m, 1H, CHH), 2.46 (s, 3H, CH), 2.56-2.74 (m, 2H, 2CHH), 2.82-2.93 (m, 1H, CHH), 5.48 (br, 1H, NCH), 7.61 (d, J=8 Hz, 1H, Ar), 7.70 (dd, J=2, 8 Hz 1H, Ar), 7.94 (br, 1H, Ar), 8.33 (s, 1H, CH), 11.15 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.72, 22.51, 30.91, 57.00 (br), 121.09, 125.38, 127.00, 135.89, 137.07, 145.46, 146.45, 159.60, 169.88, 172.44; LCMS: MH=272; Anal Calcd for C14H13N3O3: C, 61.99; H, 4.83; N, 15.49. Found: C, 61.78; H, 4.57; N, 15.34.

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