4-CHLORO-6-NITROQUINAZOLINE

Brown Solid

4-Hydroxy-6-nitroquinazoline (Compound 5) (3.8 g, 0.02 mol) was placed in a 100 ml flask, and 40 ml of thionyl chloride and 1 ml of N, N-dimethylformamide were slowly added. The mixture was heated to 90 ° C, the solid was completely dissolved, and the reaction was carried out for 3 h (detection was found to be complete at this time), and thionyl chloride was evaporated under reduced pressure to give a brown solid 4-chloro-6-nitroquinazoline (compound 6) 3.92. g, yield 93.5percent, HPLC purity 99.67percent. HNMR (300MHz, CDCl3) 89.56 (s, 1H), 8.39 (d, J = 1.5 Hz 1H), 8.76 (d, J = 1.5 Hz, J = 6.0 Hz, 1H), 8.77 (d, J = 6.0 Hz, 1H).Example 21 (^-N-(4-((3-Chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl)-4-((4aR, 7a5)-tetrahydro- 2H-[l, 4]dioxino[2, 3-c]pyrrol- Step 1) 4-chloro-6-nitroquinazoline To a solution of 6-nitroquinazolin-4-ol (9.00 g, 47.1 mmol) and TEA (9.53 g, 94.2 mmol) in toluene (200 mL) was added POCIStep 1Example 3 2.85 g (15 mmol) of 6-nitro-quinazolone and 25 ml of phosphorus oxychloride were added to a flask of 100 ml equipped with a reflux condenser and then refluxed for 3 hours at 105°C, which was then poured carefully into ice-water system of 150 ml. The squamose solid precipitated slowly. The solid was collected by filtration and dried, and was then identified as 4-chloro-6-nitro-quinazoline with a yield of 78percent. Example 3 1) 2.85 g (15 mmol) of 6-nitro-quinazolone and 25 ml of phosphorus oxychloride were added to a flask of 100 ml equipped with a reflux condenser and then refluxed for 3 hours at 105° C., which was then poured carefully into ice-water system of 150 ml. The squamose solid precipitated slowly. The solid was collected by filtration and dried, and was then identified as 4-chloro-6-nitro-quinazoline with a yield of 78percent.[[00167]] A. 2247-4. [8] gr, 25 mM, AG [2246, ] 5 ml, 25 mM, POCl3 and 5 [ML, ] 41 mM, dimethyl aniline in [50] ml toluene were refluxed 3 hours. Water and NH3 were added and the reaction extracted with ethyl acetate. Chromatography gave 0.7 gr, 13percent yield, light yellow-orange solid, mp-110°. NMR DMSOd6 [5] 9.25 [(LH, ] s, H2), 9.21 [(LH, ] d, J=2.6 Hz, [HUG), ] 8.74 [(LH, ] dd, J=9.2, 2.6 Hz, H7), 8.27 [(LH, ] d, J=9.2 Hz, H8). When the chlorination was done without dimethyl aniline, only SM was recovered.

Intermediate in the preparation of anticancer agents and enzyme inhibitors.

Molecular Weight:209.59
XLogP3:2.3
Hydrogen Bond Acceptor Count:4
Exact Mass:208.9992041
Monoisotopic Mass:208.9992041
Topological Polar Surface Area:71.6
Heavy Atom Count:14
Complexity:233
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes