Triethyl orthoacetate → 3-(2,5-dimethyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione

HRID 1409600

반응식

HRID 1409600 반응식
[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](OCC)(OCC)(OCC)[CH3:21]>CN(C=O)C>[CH3:20][C:21]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

참가 물질

4

반응물 2

HCID 66221Triethyl orthoacetateHCID 659566542-amino-N-(2,6-dioxo-piperidin-3-yl)-6-methyl-benzamide

생성물 1

HCID 249672253-(2,5-dimethyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione수율 43%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-6-methyl-benzamide (1.00 g, 3.8 mmol) and triethyl orthoacetate (0.9 mL, 4.9 mmol) in DMF (10 mL) was heated to reflux for 1 hour. The mixture was cooled to room temperature. To the solution, Celite (40 mL) was added, and the solvent was removed in vacuo. The solid was loaded on a SIM and purified with ISCO flash gel chromatography (silica gel, CH3OH/CH2Cl2) to give 3-(2,5-dimethyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as an off-white solid (0.46 g, 43% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 25/75 CH3CN/0.1% H3PO4, 2.95 min (96%); mp: 292-294° C.; 1H NMR (DMSO-d6) δ 2.11-2.18 (m, 1H, CHH), 2.55-2.65 (m, 2H, CH2), 2.60 (s, 3H, CH3), 2.69 (s, 3H, CH3), 2.78-2.85 (m, 1H, CHH), 5.19 (dd, J=6, 11 Hz, 1H, NCH), 7.25 (d, J=8 Hz, 1H, Ar), 7.43 (d, J=8 Hz, 1H, Ar), 7.64 (t, J=8 Hz, 1H, Ar), 10.99 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.82, 22.43, 23.32, 30.55, 56.33, 118.69, 124.73, 128.82, 133.72, 139.82, 148.34, 154.58, 161.03, 169.61, 172.60; LCMS: MH=286; Anal. Calcd. for C15H15N3O3+1 H2O: C, 59.26; H, 5.68; N, 13.66. Found: C, 59.26; H, 5.68; N, 13.66.

후처리

  1. temperatureto reflux for 1 hour
  2. additionTo the solution, Celite (40 mL) was added
  3. customthe solvent was removed in vacuo
  4. custompurified with ISCO flash gel chromatography (silica gel, CH3OH/CH2Cl2)

출처 및 근거

ORD 기록
ord-8032fd9c23044569987ae9077a92073d
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921385B2

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