3,6-Dichloro-4,5-dimethylpyridazine

3, 6-Dichloro-4, 5-dimethyl-pyridazine (D9); A mixture of 6-hydroxy-4, 5-dimethyl-2H-pyridazin-3-one (2.56 g, 18 mmol) (prepared by a procedure similar to that described in WO 99/36407), phosphorus oxychloride (8 ml) and diisopropylethylamine (4 ml) was stirred at 160 Until the suspension becomes alkaline, 28percent aqueous ammonium hydroxide solution was added to the suspension to produce brown precipitate. The precipitate was filtered and then dissolved in hot ethanol to remove insoluble material. Active carbon was added to the resulting solution and the mixture was refluxed for 5 minutes, decolorized by passing through silicon dioxide and then distilled under reduced pressure to remove excessive ethanol. In this manner, the title compound was obtained as a white needle crystal. Yield: 2.45 g (69.2percent) Melting Point: 109-111° C. Recrystallizing solvent: ethanol NMR(CDCl3, delta): 2.05(s, 3H*2, CH3)EXAMPLE 7 Until the suspension becomes alkaline, 28percent aqueous ammonium hydroxide solution was added to the suspension to produce brown precipitate. The precipitate was filtered and then dissolved in hot ethanol to remove insoluble material. Active carbon was added to the resulting solution and the mixture was refluxed for 5 minutes, decolorized by passing through silicon dioxide and then distilled under reduced pressure to remove excessive ethanol. In this manner, the title compound was obtained as a white needle crystal. Yield: 2.45g (69.2percent) Melting Point: 109-111°C Recrystallizing solvent: ethanol NMR(CDCl3, delta): 2.05(s, 3H*2, CH3)General procedure: Pyrido[3, 4-d]pyridazine-1 , 4-diol (1 .83g, 11 .2mmol) and phosphorus oxychloride (8.4mL, 89.7mmol) were added to a round bottomed flask. To this was added DIPEA (2.OmL, 11 .2mmol) slowly. The suspension was then heated for 1 hour at 100°C. The reaction turned into a brown solution. Thephosphorus oxychloride was then removed by rotary evaporator. The resulting brown residue was dissolved in DCM and added dropwise to a mixture of ice and saturated NaHCO3 solution (aq). Saturated NaHCO3 solution (aq) was added until the aqueous layer was neutral. The organic and aqueous layers were separated and the aqueous layer was further extracted with DCM (500mL). The organic layers were combined and dried (Mg504) and then concentrated in vacuo to afford 1, 4- dichloropyrido[3, 4-d]pyridazine (1 .74g, 8.7mmol, 77.6percent).1H NMR (400MHz, ODd3) s/ppm: 9.78 (d, J0.9Hz, 1H), 9.27 (d, J5.7Hz, 1H), 8.09 (dd, J5.7Hz, 0.9Hz, 1H).MS Method 2: RT: 1 .1 6mm, ES÷ m/z 200.0/202.0 [M÷H].General procedure: Pyrido[3, 4-d]pyridazine-1 , 4-diol (1 .83g, 1 1 .2mmol) and phosphorus oxychloride (8.4ml_, 89.7mmol) were added to a round bottomed flask. To this was added DIPEA (2.0ml_, 1 1 .2mmol) slowly. The suspension was then heated for 1 hour at 1 00°C. The reaction turned into a brown solution. The phosphorus oxychloride was then removed by rotary evaporator. The resulting brown residue was dissolved in DCM and added dropwise to a mixture of ice and saturated NaHCCb solution (aq). Saturated NaHCCb solution (aq) was added until the aqueous layer was neutral. The organic and aqueous layers were separated and the aqueous layer was further extracted with DCM (500ml_). The organic layers were combined and dried (MgSCH) and then concentrated in vacuo to afford 1 , 4- dichloropyrido[3, 4-d]pyridazine (1 .74g, 8.7mmol, 78percent). 1 H NMR (400MHz, CDC ) delta/ppm : 9.78 (d, J 0.9Hz, 1 H), 9.27 (d, J 5.7Hz, 1 H), 8.09 (dd, J 5.7Hz, 0.9Hz, 1 H). MS Method 2: RT: 1 .1 6min, ES+ m/z 209.0 [M+H]+

Molecular Weight:177.03
XLogP3:2.5
Hydrogen Bond Acceptor Count:2
Exact Mass:175.9908036
Monoisotopic Mass:175.9908036
Topological Polar Surface Area:25.8
Heavy Atom Count:10
Complexity:106
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes