Tetrahydrofuran → HCID 66642978, compound

HRID 1868244Notes

Reaction equation

HRID 1868244 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.[CH:22]1([C:25](Cl)=O)C[CH2:23]1.[O:28]1CC[CH2:30][CH2:29]1>>[CH:22]1([CH2:30][C:29]([NH:1][C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[C:4](=[O:21])[N:5]([CH:13]2[CH2:18][CH2:17][C:16](=[O:19])[NH:15][C:14]2=[O:20])[C:6]([CH3:12])=[N:7]3)=[O:28])[CH2:25][CH2:23]1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 77637Cyclopropanecarbonyl chlorideHCID 24967599Avadomide

Product 1

HCID 66642978HCID 66642978, compoundYield 23%

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 (0.41 g, 1.3 mmol) in tetrahydrofuran (8 mL), was added cyclopropanecarbonyl chloride (0.24 mL, 2.7 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 2-cyclopropyl-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-yl]-acetamide as a white solid (110 mg, 23% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 35/65 CH3CN/0.1% H3PO4, 2.78 min (98.2%); mp, 239-241° C.; 1HNMR (DMSO-d6) δ 0.87 (d, J=5 Hz, 4H, CH2CH2), 1.70-1.75 (q, J=6 Hz, 1H, CH), 2.20-2.25 (m, 1H, CHH), 2.59-2.88 (m, 5H, CH, CH3), 5.33 (dd, J=6, 12 Hz, 1H, CH), 7.26-8.52 (m, 3H, Ar), 11.10 (s, 1H, NH), 12.03 (s, 1H, NH); 13C NMR (DMSO-d6) δ 7.88, 7.99, 16.26, 20.68, 23.34, 30.56, 56.73, 115.24, 120.29, 135.64, 139.80, 147.85, 154.72, 163.14, 169.34, 171.92, 172.60. LCMS MH=355; Anal Calcd For C18H18N4O4+1.7H2O: C, 56.16; H, 5.60; N, 14.55. Found: C, 55.90; H, 5.50; N, 14.31.

Workup

  1. customThe mixture was quenched with a few drops of methanol
  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-bd0367279d874c7e81ebd6ab8fc0a795
Source dataset
uspto-grants-2009_12
Patent number
US07635700B2

Reaction notes

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