4-Chlorobenzoyl chloride → HCID 24963674, compound

HRID 1868277Notes

Reaction equation

HRID 1868277 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.[Cl:24][C:25]1[CH:33]=[CH:32][C:28]([C:29](Cl)=[O:30])=[CH:27][CH:26]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[Cl:24][C:25]1[CH:33]=[CH:32][C:28]([C:29]([NH:2][CH2:3][C:4]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:5]=2[C:6](=[O:23])[N:7]([CH:15]2[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]2=[O:22])[C:8]([CH3:14])=[N:9]3)=[O:30])=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 85014-Chlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 249683051015474-47-1

Product 1

HCID 24963674HCID 24963674, compoundYield 63.5%

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 (0.48 g, 1.4 mmol) in acetonitrile (10 mL), was added 4-chloro-benzoyl chloride (0.27 mL, 2.2 mmol) and N,N-diisopropyl ethylamine (0.62 mL, 3.6 mmol). The mixture was stirred at room temp overnight. The solvent was evaporated, and the residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%) to give 4-chloro-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-benzamide as a white solid (390 mg, 62% 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, 6.18 min (98.0%); mp, 276-278° C.; 1HNMR (DMSO-d6) 2.18-2.23 (m, 1H, CHH), 2.58-2.93 (m, 6H, CHCH2, CH3), 4.97-5.08 (m, 2H, CH2NH), 5.26 (dd, J=6, 11 Hz, 1H, CH), 7.33-7.96 (m, 7H, Ar), 9.01 (t, 1H, J=6 Hz, CH2NH), 11.05 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.82, 23.29, 30.60, 42.21, 56.54, 117.66, 124.16, 125.52, 128.45, 129.17, 132.95, 133.95, 136.13, 140.69, 148.52, 154.84, 161.10, 165.23, 169.54, 172.63. LCMS MH=439, 441; Anal Calcd For C22H19N4O4Cl+0.1H2O: C, 59.96; H, 4.39; N, 12.71; Cl, 8.05. Found: C, 59.80; H, 4.13; N, 12.61; Cl, 8.30.

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-f1ad4377f3274daabc17b7c8765c1b0e
Source dataset
uspto-grants-2009_12
Patent number
US07635700B2

Reaction notes

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