7-(benzyloxy)-2,4-dichloro-6-methoxyquinazoline

General procedure: 2, 4-Dichloroquinazolines 67, 68 or 69 (1.07 mmol) and triethylamine (3.23 mmol) were added to asolution of the appropriate amine (1.18 mmol) in dry THF (10 mL) at 0 C. After 4-6.5 h of stirring at rtthe reaction was stopped, and the suspension was filtered and washed with dry THF. The filtrate and thewashes were concentrated under vacuum. The obtained crude solid was purified by silica gel columnchromatography eluting with a mixture ethyl acetate/n-hexane/methanol (4:11:1) to afford the requiredintermediate compound.To a stirred solution of 1 (100'mg, 0.3'mmol) in 10'mL dry 1, 4-dioxane, piperidine (0.1'mL, 1'mmol) was added. The solution was stirred for 3'h'at room temperature. The reaction mixture was concentrated under reduced pressure and poured into ice water. The solid formed was filtered, washed with water and dried under vacuum. The pure solid was dissolved in 10'mL dry THF and 1'mL of 2M dimethylamine in THF was added and the reaction mixture was stirred for 24'h'at 70'C in sealed tube. The reaction mixture was cooled to room temperature and THF was removed under reduced pressure. The residue was extracted with ethyl acetate (3?*?50'mL) and the combined organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to give compound 18 as a white solid (51'mg, 87% yield after two steps, m.p- 178-182'C). 1H NMR (300'MHz, CDCl3) delta 7.48 (d, J?=?6.6'Hz, 2H), 7.41-7.31 (m, 3H), 7.06 (s, 1H), 7.02 (s, 1H), 5.23 (s, 2H), 3.90 (s, 3H), 3.54 (t, J?=?4.2'Hz, 4H), 3.22 (s, 6H), 1.79-1.74 (m, 6H). 13C NMR (75'MHz, CDCl3) delta 165.1, 153.7, 144.9, 136.3, 128.5, 128.0, 127.5, 106.6, 105.3, 105.1, 70.5, 56.2, 50.9, 37.2, 25.9, 24.9. HRMS (EI) calcd for C23H28N4O2 (m/z) [M]+ 392.2212; found 392.2222.

Molecular Weight:335.2
XLogP3:4.9
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:334.0275830
Monoisotopic Mass:334.0275830
Topological Polar Surface Area:44.2
Heavy Atom Count:22
Complexity:355
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes