(4-Chlorophenyl)acetic acid → HCID 24963327, compound

HRID 1409644Notes

Reaction equation

HRID 1409644 reaction equation
[Cl: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>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([NH:25][CH2:26][C:27]2[CH:36]=[CH:35][CH:34]=[C:33]3[C:28]=2[C:29](=[O:46])[N:30]([CH:38]2[CH2:43][CH2:42][C:41](=[O:44])[NH:40][C:39]2=[O:45])[C:31]([CH3:37])=[N:32]3)=[O:11])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 15880(4-Chlorophenyl)acetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 249683051015474-47-1

Product 1

HCID 24963327HCID 24963327, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (4-chloro-phenyl)-acetic acid (0.31 g, 1.8 mmol) in DMF in a 40° C. oil bath (8 mL), was added 1,1′-carbonyldiimidazole (0.33 g, 2.0 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 (0.62 g, 1.8 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-(4-chloro-phenyl)-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-acetamide as an off-white solid (580 mg, 70% 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 (98.5%); mp, 285° C. (decomposed); 1HNMR (DMSO-d6)2.14-2.19 (m, 1H, CHH), 2.57-2.86 (m, 6H, CHCH2, CH3), 3.54 (s, 2H, ArCH2), 4.74-4.78 (m, 2H, CH2NH), 5.23 (dd, J=6, 11 Hz, 1H, CH), 7.26-7.72 (m, 7H, Ar), 8.39 (t, J=6 Hz, 1H, CH2NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.74, 23.28, 30.59, 41.49, 41.72, 56.48, 117.68, 124.72, 125.59, 128.13, 130.92, 131.08, 133.82, 135.32, 140.64, 148.44, 154.80, 160.90, 169.50, 169.88, 172.59. LCMS MH=453, 455; Anal Calcd For C23H21N4O4Cl+0.15H2O+0.06 CH2Cl2: C, 60.12; H, 4.69; N, 12.16; Cl, 8.62. Found: C, 59.78; H, 4.60; N, 12.22; Cl, 9.00.

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-95fb49c180a448e38a6f01802a0dcfe8
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

Loading…