2-(4-Fluorophenyl)acetic acid → HCID 24964022, compound

HRID 1409646Notes

Reaction equation

HRID 1409646 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

HCID 24964022HCID 24964022, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

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-0bea9e605f0e467887483a623be12d7d
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

Loading…