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

HRID 453013

반응식

HRID 453013 반응식
[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]

참가 물질

6

반응물 2

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

생성물 1

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

시약·촉매·용매 3

HCID 9942167Palladium hydroxide촉매HCID 6228Dimethylformamide용매HCID 8079Cyclohexene용매

반응 조건

온도
125 °C

실험 절차

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) δ2.08-2.14 (m, 1H, CH—H), 2.54 (s, 3H, CH3), 2.55-2.67 (m, 2H, 2CHH), 2.75-2.90 (m, 1H, CHH), 5.16 (dd, J=5, 11 Hz, 1H, NCR), 5.59 (brs, 2H, NH2), 7.04-7.08 (m, 2H, Ar), 7.31-7.34 (m, 1H, Ar), 10.97 (s, 1H, NH); 13C 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.

후처리

  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

출처 및 근거

ORD 기록
ord-c71bff9adb6b4905b041628ce3084dc5
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08492395B2

연결된 노트

불러오는 중…