Imidazole → 3-(6,8-dichloro-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione

HRID 509523노트

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HRID 509523 반응식
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:8]([Cl:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.N1[CH:17]=[CH:16]N=C1.C(Cl)(=O)C.Cl.[NH2:23][CH:24]1[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C>[Cl:12][C:8]1[CH:7]=[C:3]2[C:2](=[C:10]([Cl:11])[CH:9]=1)[N:1]=[C:16]([CH3:17])[N:23]([CH:24]1[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31])[C:4]2=[O:6]

참가 물질

7

반응물 5

HCID 795Imidazole2회HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 760363,5-Dichloroanthranilic acidHCID 1345483-Aminopiperidine-2,6-dione hydrochloride

생성물 1

HCID 252352263-(6,8-dichloro-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione수율 58%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a stirred mixture of 2-amino-3,5-dichlorobenzoic acid (5.0 g, 24 mmol) and imidazole (1.9 g, 28 mmol) in acetonitrile (60 mL), was added acetyl chloride (2.0 mL, 28 mmol) at room temperature. The mixture was stirred at room temperature overnight. To the mixture, was added 3-amino-piperidine-2,6-dione hydrogen chloride (3.9 g, 24 mmol), imidazole (3.5 g, 52 mmol) and triphenyl phosphite (6.8 mL, 26 mmol) and heated to reflux for 22 hours. The suspension was filtered and washed with acetonitrile (30 mL), water (2×30 mL), and ethyl acetate (30 mL) to give 3-(6,8-dichloro-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (4.65 g, 58% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 4.78 min (100%); mp: 238-240° C.; 1H NMR (DMSO-d6) δ 2.15-2.22 (m, 1H, CHH), 2.55-2.69 (m, 5H, CH, 2CHH), 2.78-2.91 (m, 1H, CHH), 5.33 (dd, J=6, 11 Hz, 1H, NCH), 7.96 (d, J=2 Hz, 1H. Ar), 8.15 (d, J=2 Hz, 1H, Ar), 11.09 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.63, 23.85, 30.54, 56.92, 122.55, 24.24, 130.51, 131.72, 134.38, 142.25, 156.80, 159.07, 169.12, 172.53; LCMS: MH=340, 342; Anal Calcd for C14H11N3O3Cl2: C, 49.43; H, 3.26; N, 12.35; Cl, 20.84. Found: C, 49.21; H, 3.11; N, 12.30; Cl, 19.43.

후처리

  1. temperatureheated
  2. temperatureto reflux for 22 hours
  3. filtrationThe suspension was filtered
  4. washwashed with acetonitrile (30 mL), water (2×30 mL), and ethyl acetate (30 mL)

출처 및 근거

ORD 기록
ord-9d31227c88844b00bb1833ea23f0b304
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096573B2

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