4-(2-chlorothieno[2,3-d]pyriMidin-4-yl)Morpholine Chemical Properties

storage temp. 

under inert gas (nitrogen or Argon) at 2–8 °C

4-(2-chlorothieno[2,3-d]pyriMidin-4-yl)Morpholine Usage And Synthesis

Synthesis

General procedure for the synthesis of 2-chloro-4-morpholinothieno[2,3-d]pyrimidines from morpholine and 2,4-dichlorothieno[2,3-d]pyrimidines: a 5L three-necked flask was assembled with a mechanical stirrer, an internal temperature probe, and nitrogen bubbling device, and 2,4-dichlorothieno[2,3-d]pyrimidines (91 g) and methanol (1.5 L) were added. Subsequently, morpholine (85.1 g) was added to the reaction system and the reaction mixture was stirred at room temperature for 1-2 hours. During the reaction, a small amount of the reaction solution was taken and diluted with dichloromethane/acetonitrile (DCM/ACN) and analyzed by LC/MS to monitor the consumption of raw materials. Upon completion of the reaction, water (3.0 L) was added to the reaction flask and the internal temperature was controlled to be below 25 °C. The resulting solid product was collected by vacuum filtration and washed with 500 mL of water. The washed solid was placed in a vacuum oven and dried at 66 °C for 24 h to obtain the target product 2-chloro-4-morpholinothieno[2,3-d]pyrimidine. The structure of the product was confirmed by 1H NMR (400 MHz, DMSO-d6): δ3.736 (t, J=4.8 Hz, 4H), δ3.897 (t, J=5.2 Hz, 4H), δ7.658 (d, J=6.4 Hz, 1H), δ7.682 (t, J=6.4 Hz, 4H). lcms (ESI pos) m/e 257 (M+1).

References

[1] Patent: WO2008/73785, 2008, A2. Location in patent: Page/Page column 170
[2] European Journal of Medicinal Chemistry, 2015, vol. 93, p. 64 - 73
[3] Patent: CN106831812, 2017, A. Location in patent: Paragraph 0094; 0095; 0096
[4] Journal of Medicinal Chemistry, 2011, vol. 54, # 22, p. 7815 - 7833
[5] Patent: CN103980287, 2016, B. Location in patent: Paragraph 0148; 0153; 0154