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ChemicalBook CAS DataBase List 4-(2-CHLORO-4-PYRIMIDINYL)MORPHOLINE
62968-37-0

4-(2-CHLORO-4-PYRIMIDINYL)MORPHOLINE synthesis

2synthesis methods
Morpholine

110-91-8

2,4-Dichloropyrimidine

3934-20-1

4-(2-CHLORO-4-PYRIMIDINYL)MORPHOLINE

62968-37-0

General procedure: 2,4-Dichloropyrimidine (1.0 g, 6.7 mmol) was suspended in ethanol (20 ml) under inert atmosphere, cooled to 0°C and stirred. To this suspension triethylamine (1.4 ml, 10.1 mmol) and morpholine (0.59 ml, 6.7 mmol) were added sequentially. The reaction mixture was stirred at 0°C for 3 hours. After completion of the reaction, the mixture was concentrated in vacuum, diluted with 1 M NaOH solution (20 ml) and extracted with ethyl acetate (3 x 20 ml). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated in vacuum to give a colorless solid. The crude product was recrystallized by ethyl acetate/hexane to give 2-chloro-4-morpholino pyrimidine (1.21 g, 90% yield) as a colorless solid, which did not require further purification.LC-MS (ESP) analysis showed m/z 200 [M+H]+ and retention time (R/T) = 3.26 min.

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Yield:62968-37-0 98%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in acetonitrile at 55; for 2 h;

Steps:

36.1 Step 1:

A mixture of 2,4-dichloropyrimidine (500 mg, 3.35 mmol), morpholine (292 mg, 3.35 mmol) and DIPEA (1.3 g, 10.05 mmol) in ACN (3 mL) was stirred at 55°C for 2 hours. The mixture was then concentrated in-vacuo and purified by flash chromatography on silica gel (Petroleum Ether/Ethyl Acetate = 2/1) to afford 4-(2-chloropyrimidin-4-yl)morpholine (660 mg, 98%) as a white solid. 1H NMR (300 MHz, CDCI3): d 3.66 (br s, 4H), 3.77-3.80 (m, 4H), 6.38-6.41 (m, 1H), 8.07-8.10 (m, 1H)

References:

WO2020/6497,2020,A1 Location in patent:Paragraph 00314

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