Acetonitrile--water (1/1) → 3-(6-Amino-2-methyl-4-oxo-3,4-dihydroquinazolin-3-yl)piperidine-2,6-dione

HRID 509474

Reaktionsgleichung

Reaktionsgleichung von HRID 509474
[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]=[C:7]([N+:21]([O-])=O)[CH:8]=2)[N:3]=1.CC#N.O>C1CCCCC=1.CN(C=O)C.[OH-].[OH-].[Pd+2]>[NH2:21][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([CH3:1])[N:11]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:10]2=[O:20]

Komponenten

6

Edukt 2

HCID 18373917Acetonitrile--water (1/1)HCID 687281433-(2-methyl-6-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione

Produkt 1

HCID 252357313-(6-Amino-2-methyl-4-oxo-3,4-dihydroquinazolin-3-yl)piperidine-2,6-dioneAusbeute 31 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9942167Palladium hydroxideKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8079CyclohexeneLösungsmittel

Reaktionsbedingungen

Temperatur
125 °C

Versuchsvorschrift

A suspension of 3-(2-methyl-6-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (4.1 g, 13 mmol) and 20% Pd(OH)2/C (0.9 g) in cyclohexene (20 mL) and DMF (60 mL) was heated in a 125° C. oil bath overnight. The suspension was filtered thru a pad of Celite, and washed with DMF (30 mL). The DMF solution and Charcoal (4 g) were stirred at room temperature for 5 hours. The suspension was filtered thru a pad of Celite. The solvent was removed in vacuo. To the residue, was added DMF (20 mL), and then water (80 mL) to give a suspension. The suspension was filtered and washed with water (50 mL), ethyl acetate (50 mL) and water (50 mL) to give a brown solid, which was purified with preparative HPLC (C18 5/95 for 2 minutes then gradient to 50/50 in 18 min CH3CN/H2O) to give 3-(6-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (1.15 g, 31% yield): HPLC: Waters Xterra C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% NH4HCO2, 5.31 min (99.8%); mp: 314-316° C.; 1H NMR (DMSO-d6) δ 2.08-2.14 (m, 1H, CHH), 2.54 (s, 3H, CHO, 2.55-2.67 (m, 2H, 2CHH), 2.75-2.90 (m, 1H, CHH), 5.16 (dd. J=5, 11 Hz, 1H, NCH), 5.59 (brs, 2H, NH2), 7.04-7.08 (m, 2H, Ar), 7.31-7.34 (m, 1H, Ar), 10.97 (s, 1H, NH); NMR (DMSO-d6) δ 21.06, 22.96, 30.62, 56.22, 105.89, 121.34, 122.61, 127.35, 137.89, 147.63, 149.24, 160.39, 169.68, 172.66; LCMS: MH=287; Anal Calcd for C14H14N4O3+1H2O: C, 55.26; H, 5.30; N, 18.41. Found: C, 54.99; H, 5.22; N, 18.35.

Aufarbeitung

  1. filtrationThe suspension was filtered
  2. washwashed with DMF (30 mL)
  3. filtrationThe suspension was filtered
  4. customThe solvent was removed in vacuo
  5. additionTo the residue, was added DMF (20 mL)
  6. customwater (80 mL) to give a suspension
  7. filtrationThe suspension was filtered
  8. washwashed with water (50 mL), ethyl acetate (50 mL) and water (50 mL)
  9. customto give a brown solid, which
  10. customwas purified with preparative HPLC (C18 5/95 for 2 minutes
  11. waitthen gradient to 50/50 in 18 min

Quellen und Nachweise

ORD-Eintrag
ord-80728e44855c47d08527c80912106e2e
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096573B2

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