Imidazole → HCID 24968304、化合物

HRID 1868255ノート

反応式

HRID 1868255 の反応式
[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]

参加物

8

反応物 5

HCID 795Imidazole2 回HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 66643161HCID 66643161、化合物

生成物 1

HCID 24968304HCID 24968304、化合物収率 54%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-a155042dc21e4f218cc9096b3094108d
出典データセット
uspto-grants-2009_12
特許番号
US07635700B2

反応ノート

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