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[ CAS No. 98796-51-1 ] {[proInfo.proName]}

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Chemical Structure| 98796-51-1
Chemical Structure| 98796-51-1
Structure of 98796-51-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 98796-51-1 ]

CAS No. :98796-51-1 MDL No. :MFCD00055063
Formula : C40H49N4O8P Boiling Point : -
Linear Structure Formula :- InChI Key :UNOTXUFIWPRZJX-CEXSRUIHSA-N
M.W : 744.81 Pubchem ID :9940288
Synonyms :

Calculated chemistry of [ 98796-51-1 ]

Physicochemical Properties

Num. heavy atoms : 53
Num. arom. heavy atoms : 24
Fraction Csp3 : 0.42
Num. rotatable bonds : 17
Num. H-bond acceptors : 10.0
Num. H-bond donors : 1.0
Molar Refractivity : 204.02
TPSA : 150.86 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.83 cm/s

Lipophilicity

Log Po/w (iLOGP) : 5.12
Log Po/w (XLOGP3) : 5.65
Log Po/w (WLOGP) : 6.39
Log Po/w (MLOGP) : 2.03
Log Po/w (SILICOS-IT) : 6.5
Consensus Log Po/w : 5.14

Druglikeness

Lipinski : 2.0
Ghose : None
Veber : 2.0
Egan : 2.0
Muegge : 4.0
Bioavailability Score : 0.17

Water Solubility

Log S (ESOL) : -7.23
Solubility : 0.0000438 mg/ml ; 0.0000000588 mol/l
Class : Poorly soluble
Log S (Ali) : -8.58
Solubility : 0.00000195 mg/ml ; 0.0000000026 mol/l
Class : Poorly soluble
Log S (SILICOS-IT) : -10.14
Solubility : 0.0000000535 mg/ml ; 0.0000000001 mol/l
Class : Insoluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 3.0
Synthetic accessibility : 7.01

Safety of [ 98796-51-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 98796-51-1 ]

* 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.

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

[ 98796-51-1 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 102691-36-1 ]
  • [ 40615-39-2 ]
  • [ 98796-51-1 ]
YieldReaction ConditionsOperation in experiment
95% With pyridine; trifluoroacetic acid In tetrahydrofuran at 20℃; for 12 h; 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 12 h; 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 percentyield of product in the mixture.
94% With α-picoline; trifluoroacetic acid In tetrahydrofuran at 20℃; for 12 h; 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 percentyield of product in the mixture.
94%
Stage #1: With 4-methyl-2-pentanone In acetonitrile at 20℃;
Stage #2: With 5-Phenyl-1H-tetrazole In acetonitrile at 20℃; for 8 h;
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 97percent. The reaction selectivity (HPLC area percent of the entitled compound / HPLC area percent 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: With 4-methyl-2-pentanone In acetonitrile at 20℃;
Stage #2: With 1H-tetrazole; pyridinium trifluroacetate In acetonitrile at 20℃; for 8 - 24 h;
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.
96 %Chromat. With N-ethyl-N,N-diisopropylamine; trifluoroacetic acid In tetrahydrofuran at 20℃; for 12 h; 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 percentyield of product in the mixture.

Reference: [1] Chemical Communications, 1997, # 9, p. 877 - 878
[2] Tetrahedron Letters, 1990, vol. 31, # 10, p. 1463 - 1466
[3] Journal of the Chemical Society - Perkin Transactions 1, 1998, # 4, p. 747 - 757
[4] Patent: US2003/232980, 2003, A1, . Location in patent: Page 7
[5] Patent: US2003/232980, 2003, A1, . Location in patent: Page 6
[6] Patent: US2003/232980, 2003, A1, . Location in patent: Page 6
[7] Patent: EP1582528, 2005, A1, . Location in patent: Page/Page column 8
[8] Patent: EP1582528, 2005, A1, . Location in patent: Page/Page column 8
[9] Organic Process Research and Development, 2000, vol. 4, # 3, p. 175 - 181
[10] Chemistry Letters, 1986, p. 1401 - 1404
[11] Bulletin of the Polish Academy of Sciences, Chemistry, 1987, vol. 35, # 11-12, p. 507 - 516
[12] Recueil des Travaux Chimiques des Pays-Bas, 1986, vol. 105, # 1, p. 33 - 34
[13] Nucleosides and Nucleotides, 1998, vol. 17, # 9-11, p. 1639 - 1644
[14] Patent: US2003/232980, 2003, A1, . Location in patent: Page 6
[15] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 20, p. 5355 - 5358
  • 2
  • [ 124482-92-4 ]
  • [ 40615-39-2 ]
  • [ 98796-51-1 ]
Reference: [1] Chemical Communications, 2014, vol. 50, # 56, p. 7463 - 7465
[2] Tetrahedron Letters, 1983, vol. 24, # 52, p. 5843 - 5846
[3] Journal of the American Chemical Society, 1998, vol. 120, # 48, p. 12395 - 12401
[4] Tetrahedron, 2004, vol. 60, # 41, p. 9273 - 9281
[5] Journal of the American Chemical Society, 2015, vol. 137, # 9, p. 3253 - 3264
  • 3
  • [ 40615-39-2 ]
  • [ 174647-46-2 ]
  • [ 98796-51-1 ]
Reference: [1] Tetrahedron Letters, 1996, vol. 37, # 3, p. 331 - 334
  • 4
  • [ 108-18-9 ]
  • [ 98796-51-1 ]
Reference: [1] Tetrahedron Letters, 1986, vol. 27, # 2, p. 199 - 202
[2] Tetrahedron Letters, 1983, vol. 24, # 52, p. 5843 - 5846
  • 5
  • [ 40615-36-9 ]
  • [ 98796-51-1 ]
Reference: [1] Tetrahedron, 2004, vol. 60, # 41, p. 9273 - 9281
  • 6
  • [ 50-89-5 ]
  • [ 98796-51-1 ]
Reference: [1] Tetrahedron, 2004, vol. 60, # 41, p. 9273 - 9281
  • 7
  • [ 124482-92-4 ]
  • [ 98796-51-1 ]
Reference: [1] Tetrahedron Letters, 1996, vol. 37, # 3, p. 331 - 334
  • 8
  • [ 17425-88-6 ]
  • [ 98796-51-1 ]
Reference: [1] Tetrahedron Letters, 1983, vol. 24, # 52, p. 5843 - 5846
  • 9
  • [ 921-26-6 ]
  • [ 40615-39-2 ]
  • [ 109-78-4 ]
  • [ 98796-51-1 ]
Reference: [1] Tetrahedron Letters, 1986, vol. 27, # 2, p. 199 - 202
  • 10
  • [ 56183-63-2 ]
  • [ 40615-39-2 ]
  • [ 109-78-4 ]
  • [ 98796-51-1 ]
Reference: [1] Tetrahedron Letters, 1986, vol. 27, # 20, p. 2271 - 2274
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