2-(4-Fluorophenyl)acetic acid → HCID 24964022、化合物

HRID 1409646ノート

反応式

HRID 1409646 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:25][CH2:26][C:27]1[CH:36]=[CH:35][CH:34]=[C:33]2[C:28]=1[C:29](=[O:46])[N:30]([CH:38]1[CH2:43][CH2:42][C:41](=[O:44])[NH:40][C:39]1=[O:45])[C:31]([CH3:37])=[N:32]2>CN(C=O)C>[O:45]=[C:39]1[CH:38]([N:30]2[C:29](=[O:46])[C:28]3[C:33](=[CH:34][CH:35]=[CH:36][C:27]=3[CH2:26][NH:25][C:9](=[O:11])[CH2:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[N:32]=[C:31]2[CH3:37])[CH2:43][CH2:42][C:41](=[O:44])[NH:40]1

参加物

5

反応物 3

HCID 98372-(4-Fluorophenyl)acetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 249683051015474-47-1

生成物 1

HCID 24964022HCID 24964022、化合物収率 76%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a stirred solution of (4-fluoro-phenyl)-acetic acid (0.23 g, 1.5 mmol) in DMF (8 mL) in a 40° C. oil bath, was added 1,1′carbonyldiimidazole (0.26 g, 1.6 mmol) and stirred for one hour. To the mixture, 3-(5-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.49 g, 1.5 mmol) was added, and the mixture was stirred for 15 minutes. The solvent was evaporated, and the residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%) to give N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-2-(4-fluoro-phenyl)-acetamide as a white solid (480 mg, 76% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, grad. to 95/5 in 5 min, kept 5 min, 5.83 min (99.2%); mp, decomposed at 290° C.; 1HNMR (DMSO-d6)2.12-2.19 (m, 1H, CHH), 2.57-2.91 (m, 6H, CHCH2, CH3), 3.53 (s, 2H, ArCH2), 4.68-4.83 (m, 2H, CH2NH), 5.23 (dd, J=6, 11 Hz, 1H, CH), 7.09-7.72 (m, 7H, Ar), 8.36 (t, J=6 Hz, 1H, CH2NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.74, 23.28, 30.58, 41.36, 41.70, 56.48, 114.89 (d, JC-F=21 Hz), 117.69, 124.72, 125.58, 130.86 (d, JC-F=7 Hz), 132.45 (d, JC-F=3 Hz), 133.82, 140.68, 148.44, 154.80, 160.91, 161.00 (d, JC-F=242 Hz), 169.50, 170.15, 172.59. LCMS MH=437; Anal Calcd For C23H21N4O4F: C, 63.30; H, 4.85; N, 12.84; F, 4.35. Found: C, 63.25; H, 4.66; N, 12.73; F, 4.21.

後処理

  1. stirringthe mixture was stirred for 15 minutes
  2. customThe solvent was evaporated
  3. customthe residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%)

出典と根拠

ORDレコード
ord-0bea9e605f0e467887483a623be12d7d
出典データセット
uspto-grants-2014_12
特許番号
US08921385B2

反応ノート

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