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Chemical Structure| 98796-51-1 Chemical Structure| 98796-51-1
Chemical Structure| 98796-51-1

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DMT-dT Phosphoramidite is employed in DNA synthesis, providing efficient protective groups to ensure synthesis accuracy and integrity.

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Details of DMT-dT Phosphoramidite

CAS No. :98796-51-1
Formula : C40H49N4O8P
M.W : 744.81
SMILES Code : O=C(NC(C(C)=C1)=O)N1[C@H](O2)C[C@H](OP(N(C(C)C)C(C)C)OCCC#N)[C@H]2COC(C3=CC=C(OC)C=C3)(C4=CC=C(OC)C=C4)C5=CC=CC=C5
English Name :(2R,3S,5R)-2-((Bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl (2-cyanoethyl) diisopropylphosphoramidite
MDL No. :MFCD00055063
InChI Key :UNOTXUFIWPRZJX-CEXSRUIHSA-N
Pubchem ID :9940288

Safety of DMT-dT Phosphoramidite

Application In Synthesis of DMT-dT Phosphoramidite

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 98796-51-1 ]

[ 98796-51-1 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 98796-51-1 ]
  • [ 102987-83-7 ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite] With 1H-tetrazole In acetonitrile at 20℃; for 0.166667h; Stage #2: With water In acetonitrile at 20℃; for 0.5h; Further stages.;
92% With 1H-tetrazole; water In acetonitrile at 20℃;
85% With 1H-tetrazole; water In acetonitrile at 20℃; for 0.166667h;
With 1H-tetrazole; water In acetonitrile at 20℃; for 0.5h;
With 1H-tetrazole In water; acetonitrile for 15h;
With 1H-tetrazole; water
With 1H-tetrazole; water In acetonitrile at 20℃;

  • 2
  • [ 89992-70-1 ]
  • [ 40615-39-2 ]
  • [ 98796-51-1 ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: 2-Cyanoethyl N,N-diisopropylchlorophosphoramidite With N-ethyl-N,N-diisopropylamine In dichloromethane; toluene for 0.0833333h; Stage #2: 5'-O-(4-4'-dimethoxytrityl)thymidine With dmap In dichloromethane; toluene for 0.133333h; 4; 10 General procedure: i) An activated resin obtained in Example 8 (AM-PS-Het5, 250 mg) was loaded into an HPLC column of stainless steel (75 mm x 4.6 mm). The resulting column packed with the activated resin was flushed with toluene at a flow rate of 1.00 mL/min for 15 minutes. The column was weighed (mToiuene + resin + column = 43.118 g), flushed with dichloromethane (DCM) with a flow rate of (0151) 1.00 mL/min for 15 minutes, and then weighted again (rriDCM + res n + column = 43.588 g). The void volume, Vvoid, of the system was determined to establish a connection between flow rate and estimated residence time of the liquid passing through the column. The void volume of the column was calculated using the formula: (0152) Am solvent switch 43.5588 g - 43.118 g (0153) ^void = 1.00 raL (0154) 1 3 0 867 wherein, Arrisoivent switch is the difference in mass and Apsoivent the difference in density when switching solvents, ii) a loaded resin was prepared by loading the activated resin 4 times with PCI (0.10 M) and L/,/V-diisopropylethylamine (DIPEA, 0.10 M) in DCM (2 mL) with flow rate of 1.00 mL/min for 5 minutes including DCM wash, iii) the substrate alcohol (0.10 M, 0.114 mmol) and DMAP (0.15 M, 0.171 mmol) or another base, such as PPY or 9AJ, were dissolved in DCM (1 mL) and eluted through the loaded resin with a flow rate of between 0.125 mL/min and 1.00 mL/min (residence time between 8 minutes and 1 minute), iV) fractions comprising the synthesized phosphoramidites were collected for 2.5 times the residence time.
100% Stage #1: 2-Cyanoethyl N,N-diisopropylchlorophosphoramidite With N-ethyl-N,N-diisopropylamine In dichloromethane; toluene for 0.0833333h; Stage #2: 5'-O-(4-4'-dimethoxytrityl)thymidine With dmap In dichloromethane; toluene for 0.133333h; 4; 10 General procedure: i) An activated resin obtained in Example 8 (AM-PS-Het5, 250 mg) was loaded into an HPLC column of stainless steel (75 mm x 4.6 mm). The resulting column packed with the activated resin was flushed with toluene at a flow rate of 1.00 mL/min for 15 minutes. The column was weighed (mToiuene + resin + column = 43.118 g), flushed with dichloromethane (DCM) with a flow rate of (0151) 1.00 mL/min for 15 minutes, and then weighted again (rriDCM + res n + column = 43.588 g). The void volume, Vvoid, of the system was determined to establish a connection between flow rate and estimated residence time of the liquid passing through the column. The void volume of the column was calculated using the formula: (0152) Am solvent switch 43.5588 g - 43.118 g (0153) ^void = 1.00 raL (0154) 1 3 0 867 wherein, Arrisoivent switch is the difference in mass and Apsoivent the difference in density when switching solvents, ii) a loaded resin was prepared by loading the activated resin 4 times with PCI (0.10 M) and L/,/V-diisopropylethylamine (DIPEA, 0.10 M) in DCM (2 mL) with flow rate of 1.00 mL/min for 5 minutes including DCM wash, iii) the substrate alcohol (0.10 M, 0.114 mmol) and DMAP (0.15 M, 0.171 mmol) or another base, such as PPY or 9AJ, were dissolved in DCM (1 mL) and eluted through the loaded resin with a flow rate of between 0.125 mL/min and 1.00 mL/min (residence time between 8 minutes and 1 minute), iV) fractions comprising the synthesized phosphoramidites were collected for 2.5 times the residence time.
92% With N-ethyl-N,N-diisopropylamine
75% With N-ethyl-N,N-diisopropylamine In dichloromethane at 65℃; for 0.25h; Inert atmosphere; Microwave irradiation; Sealed tube;
In tetrahydrofuran according to ref 3) with modifications;
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 25℃; for 1h;
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 2h;
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere;

  • 3
  • [ 102691-36-1 ]
  • [ 40615-39-2 ]
  • [ 98796-51-1 ]
YieldReaction ConditionsOperation in experiment
97% With chloro-trimethyl-silane In tetrahydrofuran for 1h; Ambient temperature;
95% With N,N-diisopropylamine tetrazolide In dichloromethane for 4h; Ambient temperature;
95% With 1H-tetrazole; N-ethyl-N,N-diisopropylamine In dichloromethane for 16h; Ambient temperature;
95% With pyridine; trifluoroacetic acid In tetrahydrofuran at 20℃; for 12h; C3 Comparative Examples 1-3 Comparative Examples 1-3; Three comparative phosphitylation reactions (C1-C3) comprising reacting a protected nucleoside reagent with 2-Cyanoethyl-N,N,N',N'-tetraisopropylphosphordiamidite in the presence of an pyridine-TFA activator were conducted, and the product yields of each calculated, according to the General Procedure described above for Examples 12-18. The various combinations of protected nucleoside, solvent, and yield for each of the 3 reactions are listed in Table 3. As illustrated by the yields in Table 3 (as compared to those of Tables 1 and 2), the yields associated with the methods of the present invention surprisingly tend to be at least as good, and in many embodiments, better, than those associated with comparable reactions using conventional activators comprising significantly less-hindered salts of unsubstituted pyridine.
95% With 2,4,6-trimethyl-pyridine; trifluoroacetic acid In tetrahydrofuran at 20℃; for 12h; 10 Examples 1-11 Examples 1-11; These Examples illustrate the phosphitylation of several protected nucleoside reagents with 2-Cyanoethyl-N,N,N',N'-tetraisopropylphosphordiamidite in the presence of several activators according to the present invention. Eleven phosphitylation reactions (1-11) comprising reacting a protected nucleoside reagent with 2-Cyanoethyl-N,N,N',N'-tetraisopropylphosphordiamidite in the presence of an acid-base activator according to the present invention were conducted, and the product yields of each calculated, as described in the General Procedure, below. The various combinations of protected nucleoside, activator base, activator acid, solvent, and yield for each of the 11 reactions are listed in Table 1. General Procedure: The activator base (1.1 to 1.2 equivalents) is added to the solvent and 0.95 to 1.1 equivalents of activator acid is subsequently added thereto at ambient temperature to form the activator solution. About 1 equivalent of the protected nucleoside is dissolved in about 10 equivalents of the solvent in a separate vessel and about 3 equivalents of the solvent is then distilled off under reduced pressure. About 1 to 1.2 equivalents of 2-Cyanoethyl-N,N,N',N'-tetraisopropylphosphordiamidite is added to the nucleoside mixture at ambient temperature, and the activator solution prepared previously is then added to the nucleoside mixture at ambient temperature with vigorous stirring. After 12 hours, the reaction mixture is diluted with toluene and washed with water. The organic layer is separated, dried over sodium sulfate if necessary, and concentrated under reduced pressure. The yield of the desired amidite is then calculated using HPLC techniques, that is, the resulting product mixture is run through an HPLC column using an appropriate eluent, and the area under the HPLC peaks used to determine the %yield of product in the mixture.
94% With α-picoline; trifluoroacetic acid In tetrahydrofuran at 20℃; for 12h; 9 Examples 1-11 Examples 1-11; These Examples illustrate the phosphitylation of several protected nucleoside reagents with 2-Cyanoethyl-N,N,N',N'-tetraisopropylphosphordiamidite in the presence of several activators according to the present invention. Eleven phosphitylation reactions (1-11) comprising reacting a protected nucleoside reagent with 2-Cyanoethyl-N,N,N',N'-tetraisopropylphosphordiamidite in the presence of an acid-base activator according to the present invention were conducted, and the product yields of each calculated, as described in the General Procedure, below. The various combinations of protected nucleoside, activator base, activator acid, solvent, and yield for each of the 11 reactions are listed in Table 1. General Procedure: The activator base (1.1 to 1.2 equivalents) is added to the solvent and 0.95 to 1.1 equivalents of activator acid is subsequently added thereto at ambient temperature to form the activator solution. About 1 equivalent of the protected nucleoside is dissolved in about 10 equivalents of the solvent in a separate vessel and about 3 equivalents of the solvent is then distilled off under reduced pressure. About 1 to 1.2 equivalents of 2-Cyanoethyl-N,N,N',N'-tetraisopropylphosphordiamidite is added to the nucleoside mixture at ambient temperature, and the activator solution prepared previously is then added to the nucleoside mixture at ambient temperature with vigorous stirring. After 12 hours, the reaction mixture is diluted with toluene and washed with water. The organic layer is separated, dried over sodium sulfate if necessary, and concentrated under reduced pressure. The yield of the desired amidite is then calculated using HPLC techniques, that is, the resulting product mixture is run through an HPLC column using an appropriate eluent, and the area under the HPLC peaks used to determine the %yield of product in the mixture.
94% Stage #1: N,N,N',N'-tetraisopropyl 2-cyanoethylphosphorodiamidite; 5'-O-(4-4'-dimethoxytrityl)thymidine With 4-methyl-2-pentanone In acetonitrile at 20℃; Stage #2: With 5-Phenyl-1H-tetrazole In acetonitrile at 20℃; for 8h; 1 Example 1; Synthesis of 5'-O-(4,4'-dimethoxytrityl)thymidine 3'-O-(2-cyanoethyl N,N-diisopropylphosphoroamidite) ; 2.0 g of 5'-O-(4,4'-dimethoxytrityl)thymidine (containing 0.5 equivalent of 4-methyl-2-pentanone) was mixed with 10 mL of dehydrated acetonitrile and 1.22 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, 0.05 g of 5-phenyl-1 H-tetrazole (0.1 equivalent to the molar number of a raw material) was added thereto and the resulting mixture was stirred at a room temperature 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 97%. 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 [5b] was 451,
94% Stage #1: N,N,N',N'-tetraisopropyl 2-cyanoethylphosphorodiamidite; 5'-O-(4-4'-dimethoxytrityl)thymidine With 4-methyl-2-pentanone In acetonitrile at 20℃; Stage #2: With 1H-tetrazole; pyridinium trifluroacetate In acetonitrile at 20℃; for 8 - 24h; 1; 2 Comparative Examples 1 and 2; Synthesis of 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine 3'-O-(2-cyanoethyl N,N-diisopropylphosphoroamidite) ; The reaction was conducted in the same manner as in Example 1, except that 0.024 g of tetrazole (0.1 equivalent to the molar number of a raw material: Comparative Example 1) and 0.068 g of pyridinium trifluoroacetate (0.1 equivalent to the molar number of a raw material: Comparative Example 2) were respectively used, instead of 5-phenyl-1 H-tetrazole. The reaction solution after 8 or 24 hours was analyzed according to the high performance liquid chromatography (reverse phase column, eluent: water/acetonitrile 5/5 (TEAA 250 mM), detection wavelength: 254 nm). The results are shown in Table 1.
88% With pyridinium trifluroacetate In dichloromethane at 20℃; for 3h; Inert atmosphere;
With N,N-diisopropylamine tetrazolide In dichloromethane Ambient temperature; Yield given;
With N,N-diisopropylamine tetrazolide In acetonitrile for 15h;
With 1H-tetrazole In chloroform; acetonitrile at 25℃; for 0.5h;
With chloro-trimethyl-silane Yield given;
96 %Chromat. With N-ethyl-N,N-diisopropylamine; trifluoroacetic acid In tetrahydrofuran at 20℃; for 12h; 11 Examples 1-11 Examples 1-11; These Examples illustrate the phosphitylation of several protected nucleoside reagents with 2-Cyanoethyl-N,N,N',N'-tetraisopropylphosphordiamidite in the presence of several activators according to the present invention. Eleven phosphitylation reactions (1-11) comprising reacting a protected nucleoside reagent with 2-Cyanoethyl-N,N,N',N'-tetraisopropylphosphordiamidite in the presence of an acid-base activator according to the present invention were conducted, and the product yields of each calculated, as described in the General Procedure, below. The various combinations of protected nucleoside, activator base, activator acid, solvent, and yield for each of the 11 reactions are listed in Table 1. General Procedure: The activator base (1.1 to 1.2 equivalents) is added to the solvent and 0.95 to 1.1 equivalents of activator acid is subsequently added thereto at ambient temperature to form the activator solution. About 1 equivalent of the protected nucleoside is dissolved in about 10 equivalents of the solvent in a separate vessel and about 3 equivalents of the solvent is then distilled off under reduced pressure. About 1 to 1.2 equivalents of 2-Cyanoethyl-N,N,N',N'-tetraisopropylphosphordiamidite is added to the nucleoside mixture at ambient temperature, and the activator solution prepared previously is then added to the nucleoside mixture at ambient temperature with vigorous stirring. After 12 hours, the reaction mixture is diluted with toluene and washed with water. The organic layer is separated, dried over sodium sulfate if necessary, and concentrated under reduced pressure. The yield of the desired amidite is then calculated using HPLC techniques, that is, the resulting product mixture is run through an HPLC column using an appropriate eluent, and the area under the HPLC peaks used to determine the %yield of product in the mixture.
Stage #1: 5'-O-(4-4'-dimethoxytrityl)thymidine With 1H-tetrazole In dichloromethane at 20℃; for 0.25h; Inert atmosphere; Stage #2: N,N,N',N'-tetraisopropyl 2-cyanoethylphosphorodiamidite at 20℃; for 3h;
With 1H-tetrazole; N-ethyl-N,N-diisopropylamine In acetonitrile

References: [1]Dabkowski, Wojciech; Tworowska, Izabela; Michalski, Jan; Cramer, Friedrich [Chemical Communications, 1997, # 9, p. 877 - 878].
[2]Szemzo; Szecsi; Sagi; Otvos [Tetrahedron Letters, 1990, vol. 31, # 10, p. 1463 - 1466].
[3]Mellor, Ben J.; Thomas, Eric J. [Journal of the Chemical Society. Perkin transactions I, 1998, # 4, p. 747 - 757].
[4]Current Patent Assignee: HONEYWELL INTERNATIONAL - US2003/232980, 2003, A1 Location in patent: Page 7.
[5]Current Patent Assignee: HONEYWELL INTERNATIONAL - US2003/232980, 2003, A1 Location in patent: Page 6.
[6]Current Patent Assignee: HONEYWELL INTERNATIONAL - US2003/232980, 2003, A1 Location in patent: Page 6.
[7]Current Patent Assignee: MITSUI CHEMICALS - EP1582528, 2005, A1 Location in patent: Page/Page column 8.
[8]Current Patent Assignee: MITSUI CHEMICALS - EP1582528, 2005, A1 Location in patent: Page/Page column 8.
[9]Sanghvi, Yogesh S.; Guo, Zhiqiang; Pfundheller, Henrik M.; Converso, Antonella [Organic Process Research and Development, 2000, vol. 4, # 3, p. 175 - 181].
[10]Hamamoto, Shoji; Takaku, Hiroshi [Chemistry Letters, 1986, p. 1401 - 1404].
[11]Kierzek, Ryszard; Rozek, Marek; Markiewicz, Wojciech T. [Bulletin of the Polish Academy of Sciences: Chemistry, 1987, vol. 35, # 11-12, p. 507 - 516].
[12]Nielsen, J.; Marugg, J. E.; Taagaard, M.; Boom, J. H. van; Dahl, O. [Recueil des Travaux Chimiques des Pays-Bas, 1986, vol. 105, # 1, p. 33 - 34].
[13]Dabkowski, Wojciech; Tworowska, Izabela; Michalski, Jan; Cramer, Friedrich [Nucleosides and Nucleotides, 1998, vol. 17, # 9-11, p. 1639 - 1644].
[14]Current Patent Assignee: HONEYWELL INTERNATIONAL - US2003/232980, 2003, A1 Location in patent: Page 6.
[15]Mei, Hui; Xing, Lei; Cai, Li; Jin, Hong-Wei; Zhao, Peng; Yang, Zhen-Jun; Zhang, Liang-Ren; Zhang, Li-He [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 20, p. 5355 - 5358].
[16]Tran, Ai; Zheng, Song; White, Dawanna S.; Curry, Alyson M.; Cen, Yana [Chemical Science, 2020, vol. 11, # 43, p. 11818 - 11826].
  • 4
  • [ 98796-51-1 ]
  • [ 40733-27-5 ]
  • [ 214152-30-4 ]
YieldReaction ConditionsOperation in experiment
82% With 5-(ethylthio)-1H-tetrazole for 0.5h; Milling;
With 1H-tetrazole In acetonitrile Ambient temperature;
95 % Spectr. Stage #1: 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite]; 3'-O-(t-butyldimethylsilyl)thymidine With 4 A molecular sieve; benzimidazolium triflate In acetonitrile at 25℃; for 0.05h; Stage #2: With tert.-butylhydroperoxide In toluene; acetonitrile at 25℃; for 0.0833333h;
Stage #1: 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite]; 3'-O-(t-butyldimethylsilyl)thymidine With 3 A molecular sieve In acetonitrile at 25℃; for 0.5h; Stage #2: With trichloroacetic acid In acetonitrile at 25℃; for 0.0833333h;
With 3 A molecular sieve; benzimidazolium triflate In acetonitrile at 25℃; for 0.0166667h;
With N-phenylimidazolium triflate In acetonitrile at 25℃; for 0.05h;
With benzotriazol-1-ol In acetonitrile at 20℃; for 0.5h; Inert atmosphere;
With 1-methyl-1H-imidazole; pyridinium trifluroacetate In acetonitrile
Stage #1: 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite]; 3'-O-(t-butyldimethylsilyl)thymidine With piperidine; 5-(benzylthio)-1H-tetrazole at 20℃; Inert atmosphere; Stage #2: With pyridine; iodine In water at 20℃; Inert atmosphere; 32 Example 32 Synthesis of Nucleic Acid Dimer Using Phosphoramidite Activator 32 A phosphoramidite activator 32 with 0.30 mol/L of BTT, containing 0.6% by volume of piperidine, was prepared in the same manner as in Example 1, except that the amount of piperidine to be added was 0.6% by volume, instead of 0.5% by volume. Next, 752 mg (1.01 mmol) of 5′-O-(4,4′-dimethoxytrityl)thymidine-3′-[(2-cyanoethyl)-N,N-diisopropyl]phosphoramidite (manufactured by CARBOSYNTH Limited) and 300 mg (0.84 mmol) of 3′-O-(tert-butyldimethylsilyl)thymidine obtained in Synthesis Example 2 were charged in a nitrogen atmosphere, 6.73 mL of the phosphoramidite activator 32 was added thereto, and the mixture was stirred at room temperature for 15 minutes. Thereafter, 8.42 mL (8.42 mmol) of a 1.0 mol/L iodine solution (pyridine-water (9:1)) was added thereto, and the mixture was stirred at room temperature for 15 minutes. 84 mL of ethyl acetate and 84 mL of a 5% by mass aqueous sodium thiosulfate solution were added thereto to perform liquid separation, and the aqueous layer was extracted with 42 mL of ethyl acetate. The organic layer was washed with 84 mL of a 5% by mass aqueous sodium thiosulfate solution and dried by the addition of sodium sulfate. After filtering sodium sulfate, the organic layer was removed under reduced pressure. The obtained crude product was subjected to 1H NMR measurement and purified by silica gel column chromatography (hexane:ethyl acetate=4:6, ethyl acetate:methanol=98:2) to form 506 mg of a target pale yellow crystal-like nucleic acid dimer. The NMR and the isolation yields of the crude product were 64% and 59%, respectively. Furthermore, the NMR yield was calculated from an integrated value of 5.093 ppm of a target nucleic acid dimer, based on an integrated value of 3.322 ppm of a chemical shift, using dimethyl sulfone (manufactured by FUJIFILM Wako Pure Chemical Corporation) as an internal standard material.

  • 5
  • [ 98796-51-1 ]
  • [ 171285-25-9 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multistep reaction;
  • 6
  • [ 112-53-8 ]
  • [ 98796-51-1 ]
  • [ 830322-65-1 ]
YieldReaction ConditionsOperation in experiment
66% Stage #1: 1-dodecyl alcohol; 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite] With 1H-tetrazole In acetonitrile at 20℃; for 5h; Stage #2: With pyridine; water; iodine In tetrahydrofuran; acetonitrile at 20℃; for 12h; Stage #3: With ammonia In water for 24h; 5.a; 5.b; 5.c 5'-(4,4'-dimethoxytrityl)-2'-deoxythymidine,3'-[(2-cyanoethyl)-N,N-diisopropyl)]-phosphoramidite (1 g, 1.34 mmol, 1 eq), dodecanol (0.324 g, 1.74 mmol, 1.3 eq), and tetrazole (0.122 g, 1.74 mmol, 1.3 eq) were dissolved in dry acetonitrile under nitrogen. The reaction mixture was stirred for 5 h at room temperature. A 100 mL solution of 0.02M I2 in THF/Pyr/H2O oxidized the resulting mixture. After 12 h at room temperature the solvent was removed under vacuum to yield compound 6a. To remove the cyanoethyl-protecting group to give compound 9a, the contents of the reaction flask were dissolved in 100 mL of NH4OH 30% in water and heated under stirring in a sealed tube for 24 hours. The phosphate derivative 9a (0.71 g) was isolated after purification on silicagel (MeOH/DCM 20/80). (Yield: 66%). The characterization data were consistent with the proposed structure.
  • 7
  • [ 178925-48-9 ]
  • [ 948899-56-7 ]
  • [ 951777-48-3 ]
  • [ 98796-51-1 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multistep reaction.;
  • 8
  • [ 142808-44-4 ]
  • [ CAS Unavailable ]
  • [ 98796-51-1 ]
  • [ 98796-53-3 ]
  • [ 93183-15-4 ]
  • [ 109389-30-2 ]
  • [ 102212-98-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: C10H13N2O5Pol; 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite] With 5-(benzylthio)-1H-tetrazole In acetonitrile Automated synthesizer; solid phase reaction; Stage #2: With dichloro-acetic acid Automated synthesizer; solid phase reaction; Stage #3: N-[1-[(2R,5R)-5-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-4-[2-cyanoethoxy(diisopropylamino)phosphanyl]oxy-3,3-difluoro-tetrahydrofuran-2-yl]-2-oxopyrimidin-4-yl]benzamide; N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite]; 5'-O-dimethoxytrityl-N2-isobutyryl-2'-deoxyguanosine-3'-O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite; Diisopropyl-phosphoramidous acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester; N4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine-3-O-[O-(2-cyanoethyl)-N,N-(diisopropyl)]phosphoramidite Further stages;
  • 9
  • [ 142808-44-4 ]
  • [ CAS Unavailable ]
  • [ 98796-51-1 ]
  • [ 98796-53-3 ]
  • [ 93183-15-4 ]
  • [ 109389-30-2 ]
  • [ 102212-98-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: C10H13N2O5Pol; 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite] With 5-(benzylthio)-1H-tetrazole In acetonitrile Automated synthesizer; solid phase reaction; Stage #2: With dichloro-acetic acid Automated synthesizer; solid phase reaction; Stage #3: N-[1-[(2R,5R)-5-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-4-[2-cyanoethoxy(diisopropylamino)phosphanyl]oxy-3,3-difluoro-tetrahydrofuran-2-yl]-2-oxopyrimidin-4-yl]benzamide; N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite]; 5'-O-dimethoxytrityl-N2-isobutyryl-2'-deoxyguanosine-3'-O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite; Diisopropyl-phosphoramidous acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester; N4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine-3-O-[O-(2-cyanoethyl)-N,N-(diisopropyl)]phosphoramidite Further stages;
  • 10
  • [ 142808-44-4 ]
  • [ CAS Unavailable ]
  • [ 98796-51-1 ]
  • [ 98796-53-3 ]
  • [ 93183-15-4 ]
  • [ 109389-30-2 ]
  • [ 102212-98-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: C10H13N2O5Pol; 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite] With 5-(benzylthio)-1H-tetrazole In acetonitrile Automated synthesizer; solid phase reaction; Stage #2: With dichloro-acetic acid Automated synthesizer; solid phase reaction; Stage #3: N-[1-[(2R,5R)-5-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-4-[2-cyanoethoxy(diisopropylamino)phosphanyl]oxy-3,3-difluoro-tetrahydrofuran-2-yl]-2-oxopyrimidin-4-yl]benzamide; N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite]; 5'-O-dimethoxytrityl-N2-isobutyryl-2'-deoxyguanosine-3'-O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite; Diisopropyl-phosphoramidous acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester; N4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine-3-O-[O-(2-cyanoethyl)-N,N-(diisopropyl)]phosphoramidite Further stages;
  • 11
  • [ 142808-44-4 ]
  • [ CAS Unavailable ]
  • [ 98796-51-1 ]
  • [ 98796-53-3 ]
  • [ 93183-15-4 ]
  • [ 109389-30-2 ]
  • [ 102212-98-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: C10H13N2O5Pol; 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite] With 5-(benzylthio)-1H-tetrazole In acetonitrile Automated synthesizer; solid phase reaction; Stage #2: With dichloro-acetic acid Automated synthesizer; solid phase reaction; Stage #3: N-[1-[(2R,5R)-5-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-4-[2-cyanoethoxy(diisopropylamino)phosphanyl]oxy-3,3-difluoro-tetrahydrofuran-2-yl]-2-oxopyrimidin-4-yl]benzamide; N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite]; 5'-O-dimethoxytrityl-N2-isobutyryl-2'-deoxyguanosine-3'-O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite; Diisopropyl-phosphoramidous acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester; N4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine-3-O-[O-(2-cyanoethyl)-N,N-(diisopropyl)]phosphoramidite Further stages;
  • 12
  • [ 142808-44-4 ]
  • [ CAS Unavailable ]
  • [ 98796-51-1 ]
  • [ 98796-53-3 ]
  • [ 93183-15-4 ]
  • [ 109389-30-2 ]
  • [ 102212-98-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: C10H13N2O5Pol; 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite] With 5-(benzylthio)-1H-tetrazole In acetonitrile Automated synthesizer; solid phase reaction; Stage #2: With dichloro-acetic acid Automated synthesizer; solid phase reaction; Stage #3: N-[1-[(2R,5R)-5-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-4-[2-cyanoethoxy(diisopropylamino)phosphanyl]oxy-3,3-difluoro-tetrahydrofuran-2-yl]-2-oxopyrimidin-4-yl]benzamide; N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite]; 5'-O-dimethoxytrityl-N2-isobutyryl-2'-deoxyguanosine-3'-O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite; Diisopropyl-phosphoramidous acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester; N4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine-3-O-[O-(2-cyanoethyl)-N,N-(diisopropyl)]phosphoramidite Further stages;
  • 13
  • [ 142808-44-4 ]
  • [ CAS Unavailable ]
  • [ 98796-51-1 ]
  • [ 98796-53-3 ]
  • [ 93183-15-4 ]
  • [ 109389-30-2 ]
  • [ 102212-98-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: C10H13N2O5Pol; 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite] With 5-(benzylthio)-1H-tetrazole In acetonitrile Automated synthesizer; solid phase reaction; Stage #2: With dichloro-acetic acid Automated synthesizer; solid phase reaction; Stage #3: N-[1-[(2R,5R)-5-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-4-[2-cyanoethoxy(diisopropylamino)phosphanyl]oxy-3,3-difluoro-tetrahydrofuran-2-yl]-2-oxopyrimidin-4-yl]benzamide; N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite]; 5'-O-dimethoxytrityl-N2-isobutyryl-2'-deoxyguanosine-3'-O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite; Diisopropyl-phosphoramidous acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester; N4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine-3-O-[O-(2-cyanoethyl)-N,N-(diisopropyl)]phosphoramidite Further stages;
  • 14
  • [ CAS Unavailable ]
  • [ 98796-51-1 ]
  • [ 98796-53-3 ]
  • [ 93183-15-4 ]
  • [ 109389-30-2 ]
  • [ 102212-98-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: C10H13N2O5Pol; 5'-O-(4,4'-dimethoxytrityl)-2'-deoxythymidine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite] With benzyl tetrazol-5-yl sulphide In acetonitrile Automated synthesizer; solid phase reaction; Stage #2: With dichloro-acetic acid Automated synthesizer; solid phase reaction; Stage #3: N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine-3'-O-[O-(2-cyanoethyl)-N,N'-diisopropylphosphoramidite]; 5'-O-dimethoxytrityl-N2-isobutyryl-2'-deoxyguanosine-3'-O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite; Diisopropyl-phosphoramidous acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester; N4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine-3-O-[O-(2-cyanoethyl)-N,N-(diisopropyl)]phosphoramidite Further stages;
 

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