1,1'-Carbonyldiimidazole → HCID 24963329, compound

HRID 1868268Notes

Reaction equation

HRID 1868268 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=O)[CH:5]=[CH:6][C:7]=1[Cl: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>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([NH:26][CH2:27][C:28]2[CH:37]=[CH:36][CH:35]=[C:34]3[C:29]=2[C:30](=[O:47])[N:31]([CH:39]2[CH2:44][CH2:43][C:42](=[O:45])[NH:41][C:40]2=[O:46])[C:32]([CH3:38])=[N:33]3)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 798743,4-Dichlorophenylacetic acidHCID 249683051015474-47-1

Product 1

HCID 24963329HCID 24963329, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (3,4-dichloro-phenyl)-acetic acid (0.30 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 (0.50 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 2-(3,4-dichloro-phenyl)-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-acetamide as a yellow solid (540 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, 6.41 min (98.4%); mp, 262-264° C.; 1HNMR (DMSO-d6) 2.14-2.19 (m, 1H, CHH), 2.57-2.89 (m, 6H, CHCH2, CH3), 3.57 (s, 2H, ArCH2), 4.69-4.85 (m, 2H, CH2NH), 5.24 (dd, J=6, 11 Hz, 1H, CH), 7.26-7.73 (m, 6H, Ar), 8.42 (t, J=6 Hz, 1H, CH2NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.73, 23.28, 30.60, 40.98, 41.76, 56.49, 117.70, 124.84, 125.65, 129.06, 129.55, 130.27, 130.63, 131.11, 133.82, 137.43, 140.52, 148.46, 154.81, 160.90, 169.42, 169.49, 172.59. LCMS MH=487, 489; Anal Calcd For C23H20N4O4Cl2: C, 56.69; H, 4.14; N, 11.50; Cl, 14.55. Found: C, 56.50; H, 3.95; N, 11.25; Cl, 14.29.

Workup

  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%)

Sources & evidence

ORD record
ord-a19182f4d5ab419a9c5b3643306d9d45
Source dataset
uspto-grants-2009_12
Patent number
US07635700B2

Reaction notes

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