1,1'-Carbonyldiimidazole → HCID 24964023、化合物

HRID 1409647ノート

反応式

HRID 1409647 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=O)[CH:5]=[CH:6][C:7]=1[CH3:8].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:26][CH2:27][C:28]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:29]=1[C:30](=[O:47])[N:31]([CH:39]1[CH2:44][CH2:43][C:42](=[O:45])[NH:41][C:40]1=[O:46])[C:32]([CH3:38])=[N:33]2>CN(C=O)C>[O:46]=[C:40]1[CH:39]([N:31]2[C:30](=[O:47])[C:29]3[C:34](=[CH:35][CH:36]=[CH:37][C:28]=3[CH2:27][NH:26][C:10](=[O:12])[CH2:9][C:4]3[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([F:1])[CH:3]=3)[N:33]=[C:32]2[CH3:38])[CH2:44][CH2:43][C:42](=[O:45])[NH:41]1

参加物

5

反応物 3

HCID 682631,1'-CarbonyldiimidazoleHCID 27746183-Fluoro-4-methylphenylacetic acidHCID 249683051015474-47-1

生成物 1

HCID 24964023HCID 24964023、化合物収率 74%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a stirred solution of (3-fluoro-4-methyl-phenyl)-acetic acid (0.25 g, 1.5 mmol) in DMF (8 mL) in a 40° C. oil bath, was added 1,1′carbonyldiimidazole (0.27 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 (0.50 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-(3-fluoro-4-methyl-phenyl)-acetamide as a yellow solid (500 mg, 74% 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, 6.10 min (99.3%); mp, 264-266° C.; 1HNMR (DMSO-d6)2.15-2.20 (m, 4H, CHH and CH3Ar), 2.57-2.91 (m, 6H, CHCH2, CH3), 3.51 (s, 2H, ArCH2), 4.73-4.78 (m, 2H, CH2NH), 5.23 (dd, J=6, 11 Hz, 1H, CH), 6.99-7.72 (m, 6H, Ar), 8.34 (t, J=6 Hz, 1H, CH2NH), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 13.76 (d, JC-F=3 Hz), 20.73, 23.27, 30.59, 41.60, 41.72, 56.48, 115.43 (d, JC-F=22 Hz), 117.69, 121.98 (d, JC-F=17 Hz), 124.82 (d, JC-F=7 Hz), 124.83, 125.59, 131.23 (d, JC-F=5 Hz), 133.80, 136.12 (d, JC-F=8 Hz), 140.64, 148.44, 154.80, 160.38 (d, JC-F=242 Hz), 160.91, 169.49, 169.90, 172.58. LCMS MH=451; Anal Calcd For C24H23N4O4F: C, 63.99; H, 5.15; N, 12.44; F, 4.22. Found: C, 63.61; H, 5.19; N, 12.33; F, 4.20.

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-84d29871f70c4ba489e2ea198625dba2
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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