Phenylacetyl chloride → HCID 24963325, compound

HRID 1409642Notes

Reaction equation

HRID 1409642 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[C:6](=[O:23])[N:7]([CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]1=[O:22])[C:8]([CH3:14])=[N:9]2.[C:24]1([CH2:30][C:31](Cl)=[O:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[O:22]=[C:16]1[CH:15]([N:7]2[C:6](=[O:23])[C:5]3[C:10](=[CH:11][CH:12]=[CH:13][C:4]=3[CH2:3][NH:2][C:31](=[O:32])[CH2:30][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[N:9]=[C:8]2[CH3:14])[CH2:20][CH2:19][C:18](=[O:21])[NH:17]1

Participants

5

Reactant 3

HCID 7679Phenylacetyl chlorideHCID 81531DiisopropylethylamineHCID 249683051015474-47-1

Product 1

HCID 24963325HCID 24963325, compoundYield 40.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 3-(5-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.51 g, 1.5 mmol) in acetonitrile (10 mL), was added phenyl acetyl chloride (0.22 mL, 1.7 mmol) and N,N-diisopropyl ethylamine (0.57 mL, 3.5 mmol). The mixture was stirred at room temp 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-phenyl-acetamide as a light yellow solid (254 mg, 40% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, gradient to 95/5 in 5 min, kept for 5 min, 5.70 min (98.5%); mp, 275-277° C.; 1HNMR (DMSO-d6)2.11-2.18 (m, 1H, CHH), 2.58-2.86 (m, 6H, CHCH2, CH3), 3.53 (s, 2H, CH2), 4.74-4.78 (m, 2H, CH2NH), 5.23 (dd, J=6, 11 Hz, 1H, CH), 7.21-7.71 (m, 8H, Ar), 8.35 (t, J=6 Hz, 1H, CH2NH), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.74, 23.27, 30.58, 41.69, 42.41, 56.48, 117.69, 124.70, 125.56, 126.34, 128.20, 129.03, 133.80, 136.30, 140.74, 148.44, 154.79, 160.91, 169.48, 170.23, 172.58. LCMS MH=419; Anal Calcd For C23H22N4O4+0.2H2O: C, 65.45; H, 5.35; N, 13.27. Found: C, 65.32; H, 5.04; N, 13.10.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%)

Sources & evidence

ORD record
ord-fab212e966634c52b4467306ed05ede1
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

Loading…