Electric Literature of 5018-38-2, Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps,and cheap raw materials. 5018-38-2, name is 4,6-Dichloro-5-methoxypyrimidine. A new synthetic method of this compound is introduced below.
HPLC/MS: rt=1.3 min Synthesis of 6-[4-(1,2,3,4-tetrahydro-1,8-naphthyridin-7-yl)-1-piperidinyl]-5-methoxy-4-chloro-pyrimidine: 2.2 g (12.3 mmoles) of 4,6-dichloro-5-methoxy-pyrimidine solubilized in 25 ml of dimethylacetamide and 3640 mul of diisopropylethylamine are added into a single-necked flask containing 800 mg (3.68 mmoles) of 4-(1,2,3,4-tetrahydro-1,8-naphthyridin-7-yl)-1-piperidine released from its salt. This mixture is heated at 130 C. for 2 hours then concentrated to dryness under vacuum. The residue obtained is taken up in a mixture of water, ethyl acetate and a saturated solution of sodium bicarbonate. The organic phase is separated and the aqueous phase reextracted with ethyl acetate. The combined organic phases are dried over magnesium sulphate then the solvent is evaporated off under vacuum. The residue is chromatographed on alumina eluding with a mixture of cyclohexane and acetate (80-20). 900 mg (Yield=68%) of expected product is obtained in the form of a yellow powder. Preparation of the naphthyridine in free amine form: 2.4 g of naphthyridine is displaced from its salt by 6 mass equivalents of basic amberlyst A21 resin (resin of R-NMe2 type) in a CH2Cl2/MeOH/AcOEt mixture 1/1/1 under stirring for 30 minutes. The resin is washed beforehand and left to swell for 20 minutes in this solvent mixture. This operation must be repeated 3 times for the displacement of the salt to be complete. After filtration of the resin and evaporation of the solvents, 800 mg (3.68 mmoles) of free naphthyridine is obtained. (Yield=88%). TLC: Rf0.4 [alumina, eluent: ethyl acetate cyclohexane (30-70)]1H-NMR (MeOD): ? 1.75 to 1.95 (m, 6H, NH-CH2-CH2-CH2, N-CH2-CH2-CH-CH2); 2.70 (t, 1H, CH2-CH-CH2); 2.8 (m, 2H, NH-CH2-CH2-CH2); 3.15 and 3.75 (2m, 4H, CH2-CH2-N-CH2-CH2); 3.75 (s, CH3-O); 6.4 and 7.15 (2d, 2H, CH?CH naphthyridine); 8.1 (s, 1H, N?CH-N).HPLC/MS: (rt=0.53 min and 2.56 min): 359(M); 360(MH+); 361 (M+2H++).
At the same time, in my other blogs, there are other synthetic methods of this type of compound,5018-38-2, 4,6-Dichloro-5-methoxypyrimidine, and friends who are interested can also refer to it.
Reference:
Patent; Ruxer, Jean-Marie; Lefrancois, Jean Michel; Heckmann, Bertrand; US2006/52398; (2006); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia