N,N-Diethylaniline → HCID 67282409, compound
Reaction equation
[CH3:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][C:7]([C:13]([O:15][CH3:16])=[O:14])=[CH:8][CH:9]=2)[NH:4][C:3]1=O.P(Cl)(Cl)([Cl:20])=O.C(N(CC)C1C=CC=CC=1)C.P(Cl)(Cl)(Cl)(Cl)Cl>>[Cl:20][C:3]1[N:2]([CH3:1])[C:11](=[O:12])[C:10]2[C:5](=[CH:6][C:7]([C:13]([O:15][CH3:16])=[O:14])=[CH:8][CH:9]=2)[N:4]=1Participants
Conditions
- Temperature
- 120 °C
Procedure
Into a round bottom flask was added methyl 3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate (0.48 g, 2.1 mmol) dissolved in phosphoryl chloride (20.0 mL, 214 mmol). N,N-diethylaniline (0.99 mL, 6.2 mmol) was added followed by phosphorus pentachloride (0.22 g, 1.05 mmol). The reaction mixture was heated to 120° C. and stirred for 1 d. The mixture was then cooled to rt and concentrated. The residue was poured over ice and extracted with DCM (3×). The combined organic phases were then washed with water, and brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude residue was purified by flash silica gel chromatography (0% to 50% EtOAc/hexanes) to afford methyl 2-chloro-3-methyl-4-oxo-3,4-dihydroquinazoline-7-carboxylate (0.12 g, 23%). LC-MS: (FA) ES+ 253; 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J=8.4 Hz, 1H), 8.31 (d, J=1.5 Hz, 1H), 8.10 (dd, J=8.4, 1.5 Hz, 1H), 3.98 (s, 3H), 3.78 (s, 3H).
Workup
- temperatureThe mixture was then cooled to rt
- concentrationconcentrated
- additionThe residue was poured over ice
- extractionextracted with DCM (3×)
- washThe combined organic phases were then washed with water, and brine
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe crude residue was purified by flash silica gel chromatography (0% to 50% EtOAc/hexanes)
Sources & evidence
- ORD record
- ord-53eaca5d286c409aa70277823d14bb0c
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08765773B2
Reaction notes
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