Benzoyl chloride → HCID 24964382, compound

HRID 1868281Notes

Reaction equation

HRID 1868281 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](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=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:24](=[O:31])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:9]=[C:8]2[CH3:14])[CH2:20][CH2:19][C:18](=[O:21])[NH:17]1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 81531DiisopropylethylamineHCID 249683051015474-47-1

Product 1

HCID 24964382HCID 24964382, compoundYield 36%

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 (0.59 g, 1.8 mmol) in acetonitrile (10 mL), was added benzoyl chloride (0.31 mL, 2.7 mmol) and N,N-diisopropyl ethylamine (0.77 mL, 4.4 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]-benzamide as a white solid (260 mg, 36% 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 (99.6%); mp, 247-249° C.; 1HNMR (DMSO-d6) 2.17-2.23 (m, 1H, CHH), 2.59-2.90 (m, 6H, CHCH2, CH3), 4.92-5.09 (m, 2H, CH2NH), 5.26 (dd, J=6, 12 Hz, 1H, CH), 7.47-7.94 (m, 8H, Ar), 8.93 (t, J=5 Hz, 1H, CH2NH), 11.05 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.82, 23.29, 30.60, 42.12, 56.53, 117.65, 124.01, 125.43, 127.20, 128.37, 131.30, 133.95, 134.21, 140.99, 148.50, 154.81, 161.11, 166.26, 169.54, 172.62. LCMS MH=405; Anal Calcd For C22H20N4O4+0.5H2O: C, 63.91; H, 5.12; N, 13.55. Found: C, 63.78; H, 4.82; N, 13.45.

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-53ec8e74ce6c448eae9c98923701539b
Source dataset
uspto-grants-2009_12
Patent number
US07635700B2

Reaction notes

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