With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.40191-32-0,Tetrahydro-2H-pyran-4-carbonyl chloride,as a common compound, the synthetic route is as follows.
To a 6-(5-chloro-6-methoxy-pyridin-3-yl)-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidine (97 mg, 0.196 mmol) in CH2CI2 (5 mL) was added the acid chloride tetrahydo-2H-pyran-4-carbonyl chloride (36.7 mg, 0.235 mmol) and triethylamine (0.035 mL, 0.254 mmol) at temperature between 0-10C. The reaction mixtue was stirred at ~3C for 30 min. The reaction mixture was concentrated under vacuum. Purification by preparative reverse phase Gilson HPLC and subsequent neutralization of the combined fractions over PL-HCO3 MP gave {(S)-3-[6-(5-chloro-6-methoxy-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-pyrrolidin-1 -yl}-(tetrahydro-pyran-4-yl)-methanone (38 mg, 41% yield) as a white lyophilized powder. 1H NMR (400 MHz, CDCI3-d, 298 K) delta ppm 1.56-1.68 (m, 2H) 1.86-2.04 (m, 2H) 2.20-2.40 (m, 2H) 2.50-2.72 (m, 1 H) 3.05-3.13 (m, 2H) 3.38-4.16 (m, 16H) 5.70-5.78 (m, 1 H) 7.42-7.45 (m, 1 H) 7.78-7.81 (m, 1 H) 8.61-8.66 (m, 1 H). LCMS: [M+H]+=474.2, Rt (2)= 1.52min.
40191-32-0, As the paragraph descriping shows that 40191-32-0 is playing an increasingly important role.
Reference£º
Patent; NOVARTIS AG; COOKE, Nigel Graham; FERNANDES GOMES DOS SANTOS, Paulo Antonio; FURET, Pascal; HEBACH, Christina; HOeGENAUER, Klemens; HOLLINGWORTH, Gregory; KALIS, Christoph; LEWIS, Ian; SMITH, Alexander Baxter; SOLDERMANN, Nicolas; STAUFFER, Frederic; STRANG, Ross; STOWASSER, Frank; TUFILLI, Nicola; VON MATT, Anette; WOLF, Romain; ZECRI, Frederic; WO2013/88404; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics