Dimethylformamide → HCID 24968300, compound

HRID 1409623Notes

Reaction equation

HRID 1409623 reaction equation
[CH2:1]([O:3][CH2:4][C:5]([OH:7])=O)[CH3:2].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[NH2:19][C:20]1[CH:29]=[CH:28][CH:27]=[C:26]2[C:21]=1[C:22](=[O:39])[N:23]([CH:31]1[CH2:36][CH2:35][C:34](=[O:37])[NH:33][C:32]1=[O:38])[C:24]([CH3:30])=[N:25]2>C(OCC)C.O1CCCC1>[O:38]=[C:32]1[CH:31]([N:23]2[C:22](=[O:39])[C:21]3[C:26](=[CH:27][CH:28]=[CH:29][C:20]=3[NH:19][C:5](=[O:7])[CH2:4][O:3][CH2:1][CH3:2])[N:25]=[C:24]2[CH3:30])[CH2:36][CH2:35][C:34](=[O:37])[NH:33]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 12301Ethoxyacetic acidHCID 65578Oxalyl chlorideHCID 24967599Avadomide

Product 1

HCID 24968300HCID 24968300, compoundYield 12.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethoxyacetic acid (0.39 mL, 4.2 mmol), oxalyl chloride (0.34 mL, 3.9 mmol) in diethylether (3 mL) was added DMF (0.02 mL). The mixture was stirred at room temp for two hours, followed by addition of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (0.60 g, 2.0 mmol) and tetrahydrofuran (20 mL). The mixture was refluxed overnight and then cooled and quenched by methanol (˜5 mL). 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]-2-ethoxy-acetamide as a white solid (90 mg, 12% 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, 5.75 min (99.6%); mp, 291-293° C.; 1HNMR (DMSO-d6) δ 1.23 (t, J=6 Hz, 3H, CH2CH3), 2.18-2.25 (m, 1H, CHH), 2.58-2.92 (m, 6H, CHCH2, CH3), 3.57 (q, J=7 Hz, 2H, CH2CH3), 4.01-4.12 (dd, J=16 Hz, 2H, CH2O), 5.30 (dd, J=6, 11 Hz, 1H, CH), 7.30-8.64 (m, 3H, Ar), 11.07 (s, 1H, NH), 12.52 (s, 1H, NH); 13C NMR (DMSO-d6) δ 14.61, 20.81, 23.25, 30.52, 56.64, 67.05, 70.09, 107.95, 115.13, 120.83, 135.55, 138.97, 147.90, 154.80, 162.61, 169.38, 169.54, 172.51. LCMS MH=373; Anal Calcd For C18H20N4O5: C, 58.06; H, 5.41; N, 15.05. Found: C, 57.83; H, 5.37; N, 14.92.

Workup

  1. temperatureThe mixture was refluxed overnight
  2. temperaturecooled
  3. customquenched by methanol (˜5 mL)
  4. customThe solvent was evaporated
  5. customthe residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%)

Sources & evidence

ORD record
ord-ed0892e88e624e049c1e6902ed07a561
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

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