ChemicalBook CAS DataBase List DMT-dA(bz) Phosphoramidite

DMT-dA(bz) Phosphoramidite synthesis

8synthesis methods

Product Name:DMT-dA(bz) Phosphoramidite
CAS Number:98796-53-3
Molecular formula:C47H52N7O7P
Molecular Weight:857.93

Phosphorodiamidous acid, N,N'-bis(1-methylethyl)-, 2-cyanoethyl ester

131420-63-8

N6-Benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine

64325-78-6

98796-53-3

Synthesis of (2R,3S,5R)-5-(6-benzoylamino-9H-purin-9-yl)-2-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-9H-purin-6-yl)benzamide from N-(9-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4- hydroxytetrahydrofuran-2-yl)-9H-purin-6-yl)benzamide: The general procedure for synthesizing (2R,3S,5R)-5-(6-benzoylamino-9H-purin-9-yl)-2-((bis(4-methoxyphenyl)(phenyl) Methoxy)methyl)tetrahydrofuran-3-yl(2-cyanoethyl)diisopropylphosphoramidite was carried out in the following general steps: the nucleoside was phosphorylated using the N-methylimidazole salts of [O-β-cyanoethyl-N,N,N',N'-tetraisopropylphosphoramidite] and saccharin as the activators. This was done as follows: nucleoside (1.5 mmol) was added in a flask of appropriate size and the solid was dried by azeotropic distillation twice (using a rotary evaporator) with 20 mL of pyridine. After purging the flask with argon, 15 mL of acetonitrile was added. The mixture was stirred at room temperature until a clarified solution was formed. Subsequently, [O-β-cyanoethyl-N,N,N',N'-tetraisopropylphosphoramidite] (Tetraphos) was added to the solution, followed by the N-methylimidazole salt of saccharin. The reaction mixture was stirred continuously at room temperature and the progress of the reaction was monitored by HPLC. Upon completion of the reaction, the mixture was diluted with 30 mL of ethyl acetate and the organic phase was washed sequentially with 2 x 25 mL of saturated aqueous sodium bicarbonate and 25 mL of saturated aqueous sodium chloride. The organic layer was separated and dried with anhydrous magnesium sulfate. The dried suspension was filtered and the solvent was removed using a rotary evaporator. Finally, the residue was dried under vacuum to obtain the target product as a foamy solid.

102691-36-1 Synthesis

2-Cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite

102691-36-1
382 suppliers
$6.00/1g

64325-78-6 Synthesis

64325-78-6
190 suppliers
$9.00/250mg

98796-53-3
212 suppliers
$12.00/250mg

Yield:98796-53-3 96%

Reaction Conditions:

Stage #1: N,N,N',N'-tetraisopropyl 2-cyanoethylphosphorodiamidite;N₆-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine in acetonitrile at 20;
Stage #2: with 5-Phenyl-1H-tetrazole in acetonitrile at 20; for 2 - 24 h;Product distribution / selectivity;

Steps:

2; 3; 4

Example 2; Synthesis of 5'-O-(4,4'-dimethoxytrityl)-N6-benzoyl-2'-deoxyadenosine 3'-O-(2-cyanoethyl N,N-diisopropylphosphoroamidite) ; 2.0 g of 5'-O-(4,4'-dimethoxytrityl)-N6-benzoyl-2'-deoxyadenosine was mixed with 10 mL of dehydrated acetonitrile and 1.10 g of 2-cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite (1.2 equivalent to the molar number of a raw material) was dropped to a suspension stirred at a room temperature, followed by further stirring. Then, 0.53 g of 5-phenyl-1H-tetrazole (1.2 equivalent to the molar number of a raw material) was added thereto and the resulting mixture was stirred at a room temperature for 2 hours. The reaction solution was analyzed according to the high performance liquid chromatography (reverse phase column, eluent: water/acetonitrile 5/5 (TEAA 250 mM), detection wavelength: 254 nm). As a result, the yield was 96%. The reaction selectivity (HPLC area % of the entitled compound / HPLC area % of the by-product) represented by the ratio of the entitled compound to the by-product represented by the general formula [5c] was 152, [] wherein R1 represents a 2-cyanoethyl group; R4 represents a 4,4'-dimethoxytrityl group; R5 represents a hydrogen atom; and B represents N6-benzoyl-9-adenine. Further, the reaction solution after 96 hours was analyzed. As a result, the yield was 99% and the reaction selectivity was 187.; Example 3; Synthesis of 5'-O-(4,4'-dimethoxytrityl)-N6-benzoyl-2'-deoxyadenosine 3'-O-(2-cyanoethyl N,N-diisopropylphosphoroamidite); The reaction was conducted in the same manner as in Example 2, except that the equivalent of 5-phenyl-1H-tetrazole was changed. 0.04 g of 5-phenyl-1 H-tetrazole (0.1 equivalent to the molar number of a raw material) was used and the resulting mixture was stirred for 24 hours. The reaction solution was analyzed according to the high performance liquid chromatography (reverse phase column, eluent: water/acetonitrile 5/5 (TEAA 250 mM), detection wavelength: 254 nm). As a result, the yield was 99%. The reaction selectivity (HPLC area % of the entitled compound / HPLC area % of the by-product) represented by the ratio of the entitled compound to the by-product represented by the general formula [5c] was 699.; Example 4; Synthesis of 5'-O-(4,4'-dimethoxytrityl)-N6-benzoyl-2'-deoxyadenosine 3'-O-(2-cyanoethyl N,N-diisopropylphosphoroamidite) ; The reaction was conducted in the same manner as in Example 2, except that the equivalent of 5-phenyl-1 H-tetrazole was changed. 0.22 g of 5-phenyl-1 H-tetrazole (0.5 equivalent to the molar number of a raw material) was used and the resulting mixture was stirred for 8 hours. The reaction solution was analyzed according to the high performance liquid chromatography (reverse phase column, eluent: water/acetonitrile 5/5 (TEAA 250 mM), detection wavelength: 254 nm). As a result, the yield was 99%. The reaction selectivity (HPLC area % of the entitled compound / HPLC area % of the by-product) represented by the ratio of the entitled compound to the by-product represented by the general formula [5c] was 785.

References:

EP1582528,2005,A1 Location in patent:Page/Page column 9