Imidazole → HCID 24968304, 화합물

HRID 1868255노트

반응식

HRID 1868255 반응식
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:3]=1[C:4]([OH:6])=O.N1[CH:24]=[CH:23]N=C1.C(Cl)(=O)C.Cl.[NH2:30][CH:31]1[CH2:36][CH2:35][C:34](=[O:37])[NH:33][C:32]1=[O:38].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C.O>[C:16]([O:15][C:13](=[O:14])[NH:12][CH2:11][C:7]1[CH:8]=[CH:9][CH:10]=[C:2]2[C:3]=1[C:4](=[O:6])[N:30]([CH:31]1[CH2:36][CH2:35][C:34](=[O:37])[NH:33][C:32]1=[O:38])[C:23]([CH3:24])=[N:1]2)([CH3:19])([CH3:18])[CH3:17]

참가 물질

8

반응물 5

HCID 795Imidazole2회HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 66643161HCID 66643161, 화합물

생성물 1

HCID 24968304HCID 24968304, 화합물수율 54%

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

실험 절차

To a stirred solution of 2-amino-6-(tert-butoxycarbonylamino-methyl)-benzoic acid (13.0 g, 48.8 mmol), imidazole (3.99 g, 58.6 mmol) in acetonitrile (160 mL), was added acetyl chloride (4.18 mL, 58.6 mmol), and the mixture was stirred at room temp overnight. To the mixture, e was added 3-amino-piperidine-2,6-dione hydrogen chloride (8.03 g, 48.8 mmol), imidazole (6.65 g, 97.6 mmol) and triphenyl phosphite (15.4 mL, 58.6 mmol), and the mixture was heated to reflux for 6 hours. The mixture was cooled to room temperature, and water (500 mL) was added. The suspension was filtered, washed with water (50 mL), ethyl acetate (20 mL), ether (50 mL), and suction dried to give [3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-carbamic acid tert-butyl ester as a brown solid (10.5 g, 54% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 5.50 min (98.5%); mp: 206-208° C.; 1H NMR (DMSO-d6) δ 1.40 (s, 9H, 3CH3), 2.15-2.20 (m, 1H, CHH), 2.55-2.68 (m, 5H, C3, 2C H), 2.79-2.86 (m, 1H, CHH), 4.63-4367 (m, 2H, CH2), 5.22 (dd, J=6, 11 Hz, 1H, NCH), 7.20 (t, J=6 Hz, 1H, NH), 7.32 (d, J=8 Hz, 1H, Ar), 7.48 (d, J=8 Hz, 1H, Ar), 7.76 (t, J=8 Hz, 1H, Ar), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.79, 23.27, 28.19, 30.57, 42.82, 56.47, 77.91, 117.53, 123.86, 125.33, 133.92, 141.76, 148.44, 154.76, 155.67, 161.01, 169.51, 172.59; LCMS: MH=401; Anal Calcd for C20H24N4O5+0.5H2O: C, 58.67; H, 6.15; N, 13.68. Found: C, 58.45; H, 5.88; N, 13.34.

후처리

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 6 hours
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationThe suspension was filtered
  5. washwashed with water (50 mL), ethyl acetate (20 mL), ether (50 mL), and suction
  6. customdried

출처 및 근거

ORD 기록
ord-a155042dc21e4f218cc9096b3094108d
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07635700B2

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