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

HRID 1409610

Reaktionsgleichung

Reaktionsgleichung von HRID 1409610
[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].[C:20]1(C)[CH:25]=[CH:24]C(S(O)(=O)=O)=[CH:22][CH:21]=1>CN(C=O)C>[CH2:21]([C:22]1[N:6]([CH:7]2[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]2=[O:14])[C:4](=[O:5])[C:3]2[C:2](=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:19])[N:1]=1)[CH2:20][CH2:25][CH3:24]

Komponenten

4

Edukt 2

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

Produkt 1

HCID 249675963-(2-butyl-5-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dioneAusbeute 30,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-6-methyl-benzamide (0.65 g, 2.5 mmol) and trimethyl orthopentionate (0.66 mL, 3.8 mmol) and p-toluenesulfonic acid (140 mg) in DMF (7 mL) was heated at 150° C. in a microwave oven for 20 minutes. The mixture was extracted with ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers was washed with water (50 mL), HCl (1N, 50 mL) and brine (50 mL). The solvent was removed in vacuo to give an oil, which was purified with column chromatography (Silica Gel, methanol/methylene chloride 0% gradient to 5% 15 min), and followed by reversed layer column chromatography (C-18, acetonitrile/water 0% gradient to 100% 15 min) to give 3-(2-butyl-5-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (80 mg, 10% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 grad 90/10 in 5 min CH3CN/0.1% H3PO4, 6.59 min (95.4%); mp: 190-192° C.; 1H NMR (DMSO-d6) δ 0.95 (t, J=8 Hz, 3H, CH3), 1.40-1.49 (m, 2H, CH2), 1.67-1.75 (m, 2H, CH2), 2.05-2.09 (m, 1H, CHH), 2.51-2.67 (m, 3H, CH2, CHH), 2.69 (s, 3H, CH3), 2.81-2.90 (m, 3H, CH2, CHH), 5.20 (dd, J=5, 11 Hz, 1H, NCH), 7.25 (d, J=7 Hz, 1H, Ar), 7.44 (d, J=8 Hz, 1H, Ar), 7.64 (t, J=8 Hz, 1H, Ar), 10.98 (s, 1H, NH); 13C NMR (DMSO-d6) δ 13.80, 21.11, 21.72, 22.48, 28.60, 30.50, 34.42, 55.41, 118.63, 124.98, 128.83, 133.70, 139.81, 148.25, 156.95, 161.17, 169.75, 172.65; LCMS: MH=328; Anal Calcd for C18H21N3O3: C, 66.04; H, 6.47; N, 12.84. Found: C, 65.87; H, 6.61; N, 12.89.

Aufarbeitung

  1. extractionThe mixture was extracted with ethyl acetate (50 mL) and water (50 mL)
  2. extractionThe aqueous layer was extracted with ethyl acetate (50 mL)
  3. washThe combined organic layers was washed with water (50 mL), HCl (1N, 50 mL) and brine (50 mL)
  4. customThe solvent was removed in vacuo
  5. customto give an oil, which
  6. customwas purified with column chromatography (Silica Gel, methanol/methylene chloride 0% gradient to 5% 15 min)
  7. customfollowed by reversed layer column chromatography (C-18, acetonitrile/water 0% gradient to 100% 15 min)

Quellen und Nachweise

ORD-Eintrag
ord-070f4ad9e89d4c20ba1693309bb6746b
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921385B2

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