Nucleotide and/or oligonucleotide and preparation method thereof

[0062] According to a preferred embodiment of the present invention, wherein, the method may also include the following steps:

[0063] In the second liquid reaction medium, the substance of formula (4) is contacted with the substance of formula (5) to obtain the substance of formula (6);

[0064] Formula (5)

[0065]

[0066] Formula (6)

[0067] Among them, in formula (5) and formula (6), R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 The definition of is the same as that in formula (1).

[0068] Wherein, relative to 1 mole of the substance of the formula (4), the amount of the second liquid reaction medium can be 5-50 L, and the amount of the substance of the formula (5) can be 1-10 moles; the reaction temperature can be minus 50 ° C to 50°C; the reaction time can be 0.2-10 hours.

[0069] Wherein, the second liquid reaction medium may be pyridine or a mixed solution of pyridine and one or more of dichloromethane, acetonitrile, dioxane and tetrahydrofuran. ...

[0115] This embodiment synthesizes the substance of formula (1), wherein m and n are 0, R is trityl, R 5 and R 6 for -CH 2 CH 2 CN, R 7 is tert-butyldimethylsilyl, R 8 For uracil, the substance of the formula (1) is named as Tr[U]BH 3 .

[0116] PCl 3 (468mg, 3.4mmol) was dissolved in 20ml of the seventh liquid reaction medium (tetrahydrofuran), and at -78°C, added 2,6-lutidine (1.64g, 15.3mmol) and dissolved in 20ml of the seventh liquid reaction medium Formula (9) compound (wherein n is 0, R 1 is trityl, R 7 is tert-butyldimethylsilyl and R 8 Uracil, that is, 5'-O-Tr-2'O-TBDMS-rU, purchased from Shanghai Gemma Pharmaceutical Technology Co., Ltd., 1.0g, 1.7mmol), maintained for 5min.

[0117] Then, 3-hydroxypropionitrile (905 mg, 12.8 mmol) was added dropwise for 20 min.

[0118] Then, the temperature was raised to -20°C, and BH dissolved in the seventh liquid reaction medium (tetrahydrofuran, 7ml) was added dropwise. 3 (7 mmol), after maintaining at 0°C for 30 mi...

[0121] This embodiment synthesizes the substance of formula (3), wherein, y is 0, R 1 is trityl, R 7 is tert-butyldimethylsilyl, R 8 For uracil, the substance of the formula (1) is named Tr[U]PH, specifically through the above-mentioned Tr[U]BH 3 take off R 5 、BH 3 group and R 6 to fulfill.

[0122] At room temperature, in the third liquid reaction medium (CH 3 CN, 30ml), the Tr[U]BH 3 (784mg, 1mmol) was kept in contact with triethylamine (10ml) for 15min. Then concentrated under reduced pressure and sucked dry, promptly took off Tr[U]BH 3 R in 5 (-CH 2 CH 2 CN).

[0123] At 0°C, in the fourth liquid reaction medium (dichloromethane, 170ml), the dried solid product was kept in contact with dichloroacetic acid (5mmol) and methoxytrityl alcohol (735mg, 2.1mmol) for 10min . The reaction was quenched by adding 100 ml of saturated sodium bicarbonate solution. The reaction liquid was extracted twice with dichloromethane, 50 ml each time. Combine the extracted organic...