Application of 10132-07-7 ,Some common heterocyclic compound, 10132-07-7, molecular formula is C4H3Cl2N3, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
A solution of 3-cyanobenzylaldehyde (1.0 g) and N-cyclohexyl-1,3-propane-diamine (2.4 g) in CH3OH (150 mL) was heated to 60 C. for 18 hours. After cooling to room temperature, NaBH4 (1.5 g) was slowly added to the above solution. The mixture was stirred for another 30 minutes. The mixture was then concentrated, quenched with NH4Cl (aq), and extracted with CH2Cl2. The organic layers were combined, dried with anhydrous MgSO4, and concentrated to give a residue. The residue was purified by chromatography on silica gel (EtOAc/Et3N=7/3) to afford Intermediate 201-I (1.6 g) in a 80% yield. A solution of Intermediate 201-I (1.6 g) and Boc2O (3.5 g) in CH2Cl2 (160 ml) was stirred at 25 C. for 15 hours and then concentrated. The resultant residue was purified by chromatography on silica gel (EtOAc/Hexane=1/1) to afford Intermediate 201-II as a yellow oil (2.36 g) in a 85% yield. A solution of Intermediate 201-II and LiAlH4 (2.3 g) in THF (230 mL) was stirred at 0 C. for 4 hours. After Na2SO4110H2O was added, the solution was stirred at room temperature for 0.5 hour. The solution was then filtered through a celite pad. The filtrate was dried over anhydrous MgSO4 and concentrated to give a residue. The residue was purified by column chromatography on silica gel (using MeOH as an eluant) to afford Intermediate 201-III (1.1 g) in a 50% yield. Diisopropylethylamine (1.1 mL) was added to a solution of 2,4-dichloro-6-aminopiperidine (0.41 g) and Intermediate 201-III (1.1 g) in 1-pentanol (10 mL). The reaction mixture was stirred overnight at 120 C. The solvent was removed under vacuum and the residue was purified by column chromatography on silica gel (EtOAc/Hexane=3/7) to afford 201-IV (1.0 g) in a 65% yield. To a solution of Intermediate 201-IV (1.0 g) in 1-pentanol (1 mL) was added N1-hydroxyethoxyethyl piperazine (0.25 g). After the solution was stirred at 120 C. for 8 hours, it was concentrated. The residue thus obtained was purified by column chromatography on silica gel (EtOAc/MeOH=4/1) to afford Intermediate 201-V (730 mg) in a 60% yield. A solution of 20% TFA/CH2Cl2 (5 mL) was added to a solution of Intermediate 201-V (0.73 g) in CH2Cl2 (2 mL). The reaction mixture was stirred for 5 hours at room temperature and concentrated by removing the solvent. The resultant residue was purified by column chromatography on silica gel (21% NH3 (aq)/MeOH=1/19) to afford Compound 201 (434 mg) in a 85% yield. Compound 201 was then treated with 1 M HCl (4 mL) in CH2Cl2 (2 mL) for 0.5 hour. After the solvents were removed, the residue was treated with ether and filtered to give hydrochloride salt of compound 201. CI-MS (M++1): 541.3.
In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles. 10132-07-7, 4-Amino-2,6-dichloropyrimidine, other downstream synthetic routes, hurry up and to see.
Reference:
Patent; Yen, Chi-Feng; Hu, Cheng-Kung; Chou, Ming-Chen; Tseng, Chen-Tso; Wu, Chien-Huang; Huang, Ying-Huey; Chen, Shu-Jen; King, Chi-Hsin Richard; US2006/281712; (2006); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia