Acetyl chloride → HCID 24967958, compound

HRID 1409620Notes

Reaction equation

[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:21])[N:5]([CH:13]1[CH2:18][CH2:17][C:16](=[O:19])[NH:15][C:14]1=[O:20])[C:6]([CH3:12])=[N:7]2.[C:22](Cl)(=[O:24])[CH3:23]>O1CCCC1>[O:20]=[C:14]1[CH:13]([N:5]2[C:4](=[O:21])[C:3]3[C:8](=[CH:9][CH:10]=[CH:11][C:2]=3[NH:1][C:22](=[O:24])[CH3:23])[N:7]=[C:6]2[CH3:12])[CH2:18][CH2:17][C:16](=[O:19])[NH:15]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred mixture of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (0.45 g, 1.5 mmol) in tetrahydrofuran (10 mL), was added acetyl chloride (0.63 mL, 8.8 mmol) and heated at 80° C. for one hour. The mixture was quenched with a few drops of methanol. 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-yl]-acetamide (80 mg, 16% 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, 5.15 min (98.6%); mp, 320-322° C.; 1HNMR (DMSO-d6)2.16 (s, 3H, CH3), 2.18-2.24 (m, 1H, CHH), 2.59-2.90 (m, 6H, CHCH2, CH3), 5.32 (dd, J=6, 11 Hz, 1H, CH), 7.28-8.54 (m, 3H, Ar), 11.08 (s, 1H, NH), 11.70 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.65, 23.35, 25.29, 30.57, 56.71, 107.39, 115.09, 120.38, 135.63, 139.84, 147.84, 154.71, 163.01, 168.67, 169.29, 172.60. LCMS MH=329; Anal Calcd For C16H16N4O4+2.2H2O: C, 52.23; H, 5.59; N, 15.23. Found: C, 52.20; H, 5.57; N, 15.21.

Workup

customThe mixture was quenched with a few drops of methanol
customThe solvent was evaporated
customthe residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%)

Sources & evidence

ORD record: ord-817b639e423f4ed3b0997585787e2bb0
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921385B2

Reaction notes

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