Thionyl Chloride → N-(4-oxo-2-phenylquinazolin-3(4H)-yl)adamantane-2-carboxamide

HRID 1853419

反応式

HRID 1853419 の反応式
[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[C:11](O)=[O:12])[CH2:8]2.S(Cl)(Cl)=O.[NH2:18][N:19]1[C:28](=[O:29])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[C:20]1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(N(C(C)C)CC)(C)C>>[O:29]=[C:28]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[C:20]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:19]1[NH:18][C:11]([CH:2]1[CH:1]2[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]1[CH2:4]3)[CH2:8]2)=[O:12]

参加物

5

反応物 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 3038022-Adamantanecarboxylic acidHCID 7228763-Amino-2-phenyl-4(3H)-quinazolinone

生成物 1

HCID 49872818N-(4-oxo-2-phenylquinazolin-3(4H)-yl)adamantane-2-carboxamide収率 23%

実験手順

A solution of adamantane-2-carboxylic acid (110 mg, 0.61 mmol, prepared as described in J. Med. Chem, (2007), 50(1), 149-164) in thionyl chloride (1.5 mL, 20.6 mmol) was heated at 80° C. for 90 minutes and then cooled to room temperature and concentrated under vacuum. The residue was dissolved in CH2Cl2 (3 mL) and 3-amino-2-phenylquinazolin-4(3H)-one (145 mg, 0.61 mmol, Aldrich) and diisopropylethylamine (0.2 mL, 1.14 mmol) were added. The mixture was stirred at room temperature for 2 hours and concentrated under vacuum. The residue was purified by flash chromatography (SiO2, eluted with hexanes-EtOAc, 90:10-70:30), then by preparative HPLC on a Waters Nova-Pak® HR C18 6 μm 60 {acute over (Å)} Prep-Pak® cartridge column (40 mm×100 mm) using a gradient of 10% to 100% acetonitrile in 10 mM aqueous ammonium acetate over 12 minutes at a flow rate of 70 mL/min to provide the title compound as a white powder (56 mg, 23%): 1 H NMR (300 MHz, CD3OD) δ ppm 1.21 (br. d, J=12.9 Hz, 1 H), 1.31 (br. d, J=12.9 Hz, 1 H), 1.51 (br. d, J=12.7 Hz, 1 H), 1.58-1.72 (m, 3 H), 1.73-1.91 (m, 5 H), 1.90-2.01 (m, 2 H), 2.21 (br. s, 1 H), 2.61 (br. s, 1 H), 7.44-7.56 (m, 3 H), 7.56-7.65 (m, 3 H), 7.76 (d, J=8.3 Hz, 1 H), 7.89 (ddd, J=8.4, 7.0, 1.6 Hz, 1 H), 8.27 (dd, J=7.9, 1.6 Hz, 1 H); MS (DCI) m/z 400 (M+H); Elemental analysis calculated for C25 H25N3O2.0.7 H2O: C, 72.86; H, 6.46; N, 10.20. Found: C, 72.72; H, 6.30; N, 10.06.

後処理

  1. concentrationconcentrated under vacuum
  2. dissolutionThe residue was dissolved in CH2Cl2 (3 mL)
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by flash chromatography (SiO2, eluted with hexanes-EtOAc, 90:10-70:30)
  5. customover 12 minutes

出典と根拠

ORDレコード
ord-7819cfb0f6e44fec80a8fad768552628
出典データセット
uspto-grants-2015_02
特許番号
US08962639B2

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