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Chemical Structure| 54-42-2
Chemical Structure| 54-42-2
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Product Details of [ 54-42-2 ]

CAS No. :54-42-2 MDL No. :MFCD00134656
Formula : C9H11IN2O5 Boiling Point : -
Linear Structure Formula :- InChI Key :XQFRJNBWHJMXHO-RRKCRQDMSA-N
M.W : 354.10 Pubchem ID :5905
Synonyms :
5-Iodo-2′-deoxyuridine;5-IUdR;Idoxuridin;5-Iododeoxyuridine;54-42-2;5-Iodo-2'-deoxyuridine;SKF 14287;NSC 39661;IdUrd

Calculated chemistry of [ 54-42-2 ]

Physicochemical Properties

Num. heavy atoms : 17
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.56
Num. rotatable bonds : 2
Num. H-bond acceptors : 5.0
Num. H-bond donors : 3.0
Molar Refractivity : 65.82
TPSA : 104.55 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -9.14 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.22
Log Po/w (XLOGP3) : -0.96
Log Po/w (WLOGP) : -1.54
Log Po/w (MLOGP) : -0.99
Log Po/w (SILICOS-IT) : 0.47
Consensus Log Po/w : -0.36

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.56
Solubility : 9.76 mg/ml ; 0.0276 mol/l
Class : Very soluble
Log S (Ali) : -0.75
Solubility : 62.9 mg/ml ; 0.178 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.96
Solubility : 38.6 mg/ml ; 0.109 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.73

Safety of [ 54-42-2 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 54-42-2 ]

* 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 [ 54-42-2 ]
  • Downstream synthetic route of [ 54-42-2 ]

[ 54-42-2 ] Synthesis Path-Upstream   1~20

  • 1
  • [ 54-42-2 ]
  • [ 36792-88-8 ]
  • [ 696-07-1 ]
  • [ 66-22-8 ]
Reference: [1] Pharmazie, 1980, vol. 35, # 10, p. 602 - 604
  • 2
  • [ 54-42-2 ]
  • [ 17039-17-7 ]
  • [ 696-07-1 ]
Reference: [1] Biochemical Journal, 2012, vol. 445, # 1, p. 113 - 123
  • 3
  • [ 951-78-0 ]
  • [ 696-07-1 ]
  • [ 54-42-2 ]
  • [ 66-22-8 ]
Reference: [1] Journal of Molecular Catalysis B: Enzymatic, 2013, vol. 95, p. 16 - 22
  • 4
  • [ 951-78-0 ]
  • [ 54-42-2 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 14, p. 3591 - 3596
[2] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 11, p. 2035 - 2038
[3] Canadian Journal of Chemistry, 1994, vol. 72, # 9, p. 2005 - 2010
[4] Canadian Journal of Chemistry, 1994, vol. 72, # 9, p. 2005 - 2010
[5] Synthesis, 2009, # 23, p. 3957 - 3962
[6] Nucleosides, Nucleotides and Nucleic Acids, 2009, vol. 28, # 9, p. 821 - 834
[7] Journal of Organic Chemistry, 1990, vol. 55, # 16, p. 4928 - 4933
[8] Canadian Journal of Chemistry, 1982, vol. 60, p. 554 - 557
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[10] Synthetic Communications, 1990, vol. 20, # 21, p. 3391 - 3394
[11] Biochimica et Biophysica Acta, 1959, vol. 32, p. 295
[12] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1985, vol. 39, # 6 B, p. 501 - 504
[13] Nucleosides, Nucleotides and Nucleic Acids, 2011, vol. 30, # 10, p. 753 - 767
  • 5
  • [ 1956-30-5 ]
  • [ 54-42-2 ]
Reference: [1] Journal of Organic Chemistry, 1990, vol. 55, # 16, p. 4928 - 4933
[2] Nucleosides, Nucleotides and Nucleic Acids, 2009, vol. 28, # 9, p. 821 - 834
  • 6
  • [ 65505-76-2 ]
  • [ 51592-06-4 ]
  • [ 54-42-2 ]
Reference: [1] Patent: US4851520, 1989, A,
  • 7
  • [ 696-07-1 ]
  • [ 50-89-5 ]
  • [ 54-42-2 ]
  • [ 65-71-4 ]
Reference: [1] Chemistry Letters, 2006, vol. 35, # 2, p. 232 - 233
  • 8
  • [ 13030-62-1 ]
  • [ 54-42-2 ]
Reference: [1] Journal of Organic Chemistry, 1990, vol. 55, # 16, p. 4928 - 4933
  • 9
  • [ 146629-34-7 ]
  • [ 54-42-2 ]
Reference: [1] Journal of Labelled Compounds and Radiopharmaceuticals, 1994, vol. 34, # 6, p. 513 - 522
  • 10
  • [ 951-78-0 ]
  • [ 696-07-1 ]
  • [ 54-42-2 ]
Reference: [1] Collection of Czechoslovak Chemical Communications, 1994, vol. 59, # 10, p. 2303 - 2330
  • 11
  • [ 624-67-9 ]
  • [ 54-42-2 ]
  • [ 504-17-6 ]
YieldReaction ConditionsOperation in experiment
25% With triethylamine In <i>N</i>-methyl-acetamide; ethyl acetate EXAMPLE IV
3-(5'-Iodo-2'-deoxyuridin-3'-yl)prop-2-enal
5-Iodo-2'-deoxyuridine (142 mg; 0.4 mmole) in dimethylformamide (2 ml) is treated with triethylamine (56 μl, 0.4 mmole) and the mixture is stirred at room temperature for 1 hr. then cooled to -70° C. Propargyl aldehyde (40 μl; 0.8 mmole) is added in one portion, stirring is continued for 1 hr. and the solution is allowed to warm slowly to 10° C.
The solvent and triethylamine are removed at room temperature under reduced pressure and the residue is chromatographed on two 20*20 cm preparative TLC plates (silica gel).
The eluding solvent used is ethyl acetate and the band running just head of starting material gives a positive thiobarbituric acid test.
This is removed and the silica gel extracted with methanol.
Removal of the solvent affords the title compound as an almost colorless glassy solid (40 mg; 25percent yield) by pure TLC analysis. 1 H-NMR (DMSO) 6.09 (t, J=6.1 Hz, 1H, --CH(O) N).
7.04 (q,J=7.8 Hz, J2 =14.8 Hz, 1H CH=CHCHO) 8.5 (d,J=14.8 Hz, 1H, --CH=CH--CHO) 8.59 (s, 1H, N--CH)=C(I) 9.60 (d,J=7.7 Hz, 1H, CH=CH--CHO).
Mass spectrum m/z (intensity, percent base peak), ion: 408 (0.1)+, 379 (9.1) (M-CHO)+ 354 (0.1) (M--CH=CH--CHO)+ 317 (27.8), 263 (53) 195 (31.5) 117 (100).
Reference: [1] Patent: US4689321, 1987, A,
  • 12
  • [ 54-42-2 ]
  • [ 69304-47-8 ]
Reference: [1] Tetrahedron, 1987, vol. 43, # 20, p. 4601 - 4608
[2] RSC Advances, 2015, vol. 5, # 31, p. 24558 - 24563
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 23, p. 5618 - 5623
  • 13
  • [ 193631-86-6 ]
  • [ 54-42-2 ]
  • [ 37972-24-0 ]
Reference: [1] Patent: US5645985, 1997, A,
  • 14
  • [ 14719-21-2 ]
  • [ 54-42-2 ]
  • [ 115899-40-6 ]
YieldReaction ConditionsOperation in experiment
76%
Stage #1: With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide for 0.166667 h; Inert atmosphere
Stage #2: With triethylamine In N,N-dimethyl-formamide at 20℃;
To a solution of 5-iodouridine A (5.0 g, 14.1 mmol) in anhyd. DMF (4OmL), CuT (0.20g.1.05 mmol) and Pd(PPh3)4 (0.41g, 0.O3Smmol) were added under nitrogen. After stirring for 10 mi triethylamine ( 4.0 mL28.6 mmol) and trifluoro-N-prop-2-ynyl-acetamide (5.4g, 35.7 mmol) were added and the reaction mixture was stirred overnight at room temperature. All the volatiles were removed under vacuum and the residue was purified by flash chromatography on silica gel [EtOAc/MeOH (0-15percent)j to afford the desired product as yellow solid 4.ig (76percent). 1H- NMR (DMSO-d6) 11.68, (br s, 1H, NH), 10.02 (s, 1H, NH), 7.94 (s, 7.94 (s, 1H, H6), 6.11 (t, J = 7.2Hz, H-i’), 5.29 (d, J= 0.4 Hz, 1H, OH), 4.21 (m, 3H, H-3’, NCH2), 3.71-3.83 (m, 2H, CH2-5’), 2.15-2.19 (m, 1H, H-2’), 2.03-2.08 (m, 1H, H-2’), Mass, Calcd for C14H14F3N306 (M+Na), 400, Found 400.
71%
Stage #1: With copper(l) iodide; triethylamine In N,N-dimethyl-formamide for 0.0833333 h; Darkness
Stage #2: at 20℃; for 16 h;
To a solution of 5-iodo-2’-deoxyuridine (1.05 g, 2.96 mmol) and CuI (114 mg, 0.60 mmol) in dry DMF (21 ml)was added triethylamine (0.9 ml). After stirring for 5 min trifluoro-N-prop-2-ynyl-acetamide (1.35 g, 9.0 mmol) andPd(PPh3)4 (330 mg, 0.29 mmol) were added to the mixture and the reaction was stirred at room temperature in the darkfor 16 h. Metanol (MeOH) (40 ml) and bicarbonate dowex added to the reaction mixture and stirred for 45 min. Themixture was filtered and the filtrate washed with MeOH and the solvent was removed under vacuum. The crude mixturewas purified by chromatography on silica (ethyl acetate (EtOAc) to EtOAc:MeOH 95:5) to give slightly yellow crystals(794 mg, 71 percent). 1H NMR (d6 dimethylsulfoxide (DMSO)) δ 2.13-2.17 (m, 2H, H-2’), 3.57-3.65 (m, 2H, H-5’), 3.81-3.84(m, 1H, H-4’), 4.23-4.27 (m, 3H, H-3’, CH2N) , 5.13 (t, J = 5.0 Hz, 1H, OH), 5.20 (d, J = 4.3 Hz, 1H, OH), 6.13 (t, J = 6.7Hz, 1H, H-1’), 8.23 (s, 1H, H-6), 10.11 (t, J = 5.6 Hz, 1H, NH), 11.70 (br s, 1H, NH). Mass (-ve electrospray) calcd forC14H14F3N3O6 377.08, found 376.
61% With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere To a one-necked flask was added F1 (0.7 mmol, 247 mg) 9.7 mg CuI and 20.3 mg Pd(PPh3)4 were weighed (Tetrakis(triphenylphosphine)palladium) was added to the reaction flask, evacuated, nitrogen protected, Aluminum box wrapped, by adding 2.3ml DMF, stirring dissolved, 0.20 ml of TEA (triethylamine) was added, Fill F2 (254mg, 1.7mmol) with DMF dissolved in the reaction flask, stirring at room temperature, the reaction overnight. TLC plate monitoring, EA for the agent, Rf = 0.35 for the raw material F1, Rf=0.32 for the product F3, two very close to the location. After the completion of the reaction, the solvent was evaporated under reduced pressure, and the residue was separated by direct column chromatography, 20:1 DCM: ΜeOΗ for eluent, was 214mg, yield 61percent.
61%
Stage #1: With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamideInert atmosphere
Stage #2: With triethylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere
F1 (0.7 mmol, 247 mg) was added to a single-necked flask and 9.7 mg CuI and 20.3 mg Pd (PPh3) 4 (tetrakistriphenylphosphine) palladium were weighed into a reaction flask. The reaction flask was evacuated, purged with nitrogen and wrapped in aluminum foil , 2.3 ml DMF was added,Stirring to dissolve, adding 0.2ml TEA, weighing F2 (254mg, 1.7mmol) dissolved in DMF was added to the above reaction flask, stirred at room temperature, the reaction overnight.TLC plate monitoring, EA as developing solvent, Rf = 0.35 as the raw material F1, Rf = 0.32 for the product F3, two very close position.After the reaction was over, the solvent was evaporated to dryness under reduced pressure and the residue was directly purified by column chromatography. Elution with 20: 1 DCM: MeOH as eluant gave 214 mg, yield 61percent.
37% With triethylamine In N,N-dimethyl-formamide Starting with 5-iodouridine 6 the compound 9 was made in a 5 step synthesis. First, Sonogashira coupling (JACS 2005, 127, 15071) with propargylamine trifluoroacetamide, copper iodide and tetrakistriphenylphosphine palladium (0) in DMF with triethylamine gave 5-propargyl(trifluoroacetamide) nucleotide 7 in 37percent yield after silica chromatography. The nucleoside was dried well and the 5'DMT group was added by using DMT chloride in dry pyridine to give 8 in 87percent yield after chromatography. The TFA amine protecting group was removed with methylamine in ethanol, to give 5-propargylamine nucleoside. Next, BHQ1 C3 carboxylic acid was added to the amine nucleoside with BOP and N-methylmorpholine to produce 5'-DMTdU-5-alkynyl(BHQ1) nucleoside 11. After drying by evaporation from pyridine, the nucleoside 11 was converted into 5'-DMTdU-5-alkynyl(BHQ1)3'-diisopropyl cyanoethyl phosphoramidite 12 with tetraisopropyl cyanoethyl phosphoramidite and tetrazole in a mixture of dry acetonitrile and dichloromethane. After purification on a silica column with a gradient of methanol in dichloromethane with 2percent pyridine, 700 mg of 12 were obtained. The phosphramidite was coupled to 5'-TTTTTTTTTT-3' immobilized on CPG with standard phosphoramidite chemistry. Analysis of the product by ESMS showed a mass of 3809.5 AMU (Calc'd 3808.5).

Reference: [1] Tetrahedron, 2009, vol. 65, # 4, p. 934 - 939
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[3] Helvetica Chimica Acta, 2007, vol. 90, # 6, p. 1082 - 1098
[4] Journal of the American Chemical Society, 2011, vol. 133, # 8, p. 2463 - 2480
[5] Helvetica Chimica Acta, 2008, vol. 91, # 1, p. 165 - 175
[6] Patent: WO2016/182984, 2016, A1, . Location in patent: Paragraph 00123
[7] Chemical Communications, 2005, # 36, p. 4551 - 4553
[8] Patent: EP2607369, 2015, B1, . Location in patent: Paragraph 0130
[9] Angewandte Chemie - International Edition, 2008, vol. 47, # 5, p. 967 - 970
[10] Patent: CN104003902, 2016, B, . Location in patent: Paragraph 0090-0092
[11] Patent: CN104292117, 2016, B, . Location in patent: Paragraph 0358; 0368; 0372-0374
[12] European Journal of Organic Chemistry, 2010, # 17, p. 3229 - 3236
[13] Patent: US2009/259030, 2009, A1, . Location in patent: Page/Page column 28-29
[14] Journal of the American Chemical Society, 1990, vol. 112, # 11, p. 4324 - 4330
[15] Journal of the American Chemical Society, 1999, vol. 121, # 42, p. 9781 - 9789
[16] Organic and Biomolecular Chemistry, 2009, vol. 7, # 18, p. 3826 - 3835
[17] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 16, p. 4384 - 4390
  • 15
  • [ 54-42-2 ]
  • [ 115899-40-6 ]
Reference: [1] Patent: US9096856, 2015, B2,
  • 16
  • [ 54-42-2 ]
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Reference: [1] Patent: US5596091, 1997, A,
  • 17
  • [ 54-42-2 ]
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  • [ 59-14-3 ]
Reference: [1] Tetrahedron Letters, 1999, vol. 40, # 31, p. 5721 - 5724
  • 18
  • [ 75-77-4 ]
  • [ 598-73-2 ]
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  • [ 70523-31-8 ]
Reference: [1] Journal of Medicinal Chemistry, 1982, vol. 25, # 11, p. 1329 - 1334
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  • [ 18162-48-6 ]
  • [ 134218-81-8 ]
YieldReaction ConditionsOperation in experiment
90% With 1H-imidazole In N,N-dimethyl-formamide at 0℃; To a solution of 5-iodo-2’-deoxyuridine (5.0 g, 14 mmol) in 70 ml in dry N,N-dimethylformamide (DMF) wasadded imidazole (1.09 g, 16 mmol), followed by (2.41 g, 16 mmol) TBDMSCl at 0 °C. The mixture was left in the ice bathand stirred overnight. The reaction was quenched with sat. aq. NaCl solution and extracted with EtOAc. After drying(MgSO4), the solvent was removed and the crude mixture was purified by chromatography on silica (EtOAc:petroleumether 3:7). The product (33) (5.9 g, 90 percent) was obtained as a colourless solid. 1H NMR (d6 DMSO) δ 0.00 (s, 3H, CH3),0.79 (s, 9H, tBu), 1.88-1.97 (m, 1H, H-2’), 2.00-2.05 (m, 1H, H-2’), 3.59-3.71 (m, 2H, H-5’), 3.75 (br s, 1H, H-4’), 4.06(br s, 1H, H-3’), 5.18 (d, J = 4.0 Hz, 1H, OH), 5.98 (t, J = 5.9 Hz, 1H, H-1’), 7.89 (s, 1H, H-6), 11.62 (s, 1H, NH). Mass(-ve electrospray) calcd for C15H25IN2O5Si 468.06 found 467.
88% With 1H-imidazole In N,N-dimethyl-formamide at 20℃; 5-Iodo-5'-0-/ert-butyldimethylsilyl-thymidine (T2): A mixture of 5-iodo-2'- deoxythymidine (Tl, 1 g, 2.8 mmol), fert-butyldimethylsilyl chloride (453 mg, 3.0mmol) and imidazole (199 mg, 3.0 mmol) was dissolved in dry DMF(15 inL) and stirred at room temperature overnight. The reaction mixture was poured into ice water (200 mL) under stirring and the precipitate was collected by suction filtration, then washed with water and hexane. The obtained crude product was purified by column chromatography (dichloromethane/methanol: 20: 1) to give 5-iodo-5'-0-/ert- butyldimethylsilyl-thymidine (T2, 1.152 g, 88 percent). 'H NMR (400 MHz, CDCI3) δ 8.19 (s, 1H), 8.12 (s, 1H), 6.36 - 6.27 (m, 1H), 4.51 (dd, J = 5.7, 2.9 Hz, 1H), 4.11 (q, J= 2.5 Hz, 1H), 4.04 - 3.83 (m, 2H), 2.45 (ddd, J = 13.5, 5.7, 2.3 Hz, 1H), 2.14 (ddd, J = 13.6, 8.0, 5.8 Hz, 1H), 1.86 (d, J = 3.5 Hz, 1H), 0.97 (s, 9H), 0.19 (d, J= 6.7 Hz, 6H).
79% With 1H-imidazole; dmap In N,N-dimethyl-formamide at -5 - 20℃; for 3 h; Inert atmosphere General procedure: To a solution of (1) (3.2 g, 17.24 mmol, 1 eq.) dissolved in anhydrous DMF (30 mL), cooled at -5 °C, imidazole (56.89 mmol, 3.3 eq.) and DMAP (2.24 mmol, 0.13 eq.) were added, followed by a solution of tert-butyldimethylsilane chloride (1.1 eq.) dissolved in anhydrous DMF (15 mL).
The reaction mixture was stirred at -5 °C for 30 min and then at room temperature for 2 h 30 min.
An aqueous saturated ammonium chloride solution (60 mL) was added and the reaction mixture was extracted with ethyl acetate (3 * 30 mL).
The combined organic layers were washed with water (40 mL), brine (2 * 30 mL), dried over sulfate magnesium, filtered and evaporated under reduced pressure.
The crude product was purified on silica gel eluted by ethyl acetate/cyclohexane (10/90, v/v) to afford compound (3) (4.5 g, 14.92 mmol). Yield: 87percent; 4.3.1
5-Iodo-5'-O-tert-butyldimethylsilyl-2'-deoxyuridine (6)
Compound (6) was synthesized from 5-iodo-2'-deoxyuridine (4.5 g, 12.70 mmol) according to the previous described protocol to synthesize compound (3).
The crude product was purified on silica gel eluted with a gradient of dichloromethane/ethyl acetate (60/40 to 50/50, v/v) to afford product (6) (4.68 g, 9.99 mmol). Yield: 79percent; Mp: 223 +- 1 °C; IR (KBr) ν (cm-1) 3568, 3173, 2953, 2852, 1733 (CO), 1676 (CO), 1608, 1261, 1119; 1H NMR (200 MHz, acetone-d6) δppm 10.37 (brs, 1H, NH), 8.13 (s, 1H, H-6), 6.23 (dd, 3J = 9.1 Hz, 3J = 5.2 Hz, 1H, H-1'), 4.43 (m, 1H, H-3'), 4.01 (m, 1H, H-4'), 3.90 (m, 2H, H-5'), 2.27 (m, 2H, H-2'), 0.95 (s, 9H, H-9), 0.17 (s, 3H, H-7 or H-7'), 0.16 (s, 3H, H-7 or H-7').
79% at 20℃; A mixture of IUdR (2.54g, 7.17 mmol) and TBDMSC1 (1.35g, 8.97 mmol) in 25 mL of pyridine was stirred at room temperature overnight. Methanol (2 mL) was added and the solvent removed under reduced pressure. The residue was dissolved in DCM (30 mL), washed with water, dried over MgS04, filtered, and the solution evaporated. A crude product was purified by column chromatography on a silica gel with a gradient of MeOH in DCM (0.3-0.7: 10) to give 2.65g (79percent yield) of compound (4); Rfvalue 0.54 (DCM/MeOH, 10:0.5). MR (DMSO-d6, 500MHz) δ 11.57 (s, 1H, H), 7.78 (s, 1H, H6-uridine), 6.07 (dd, HI ', · = 5.45 Hz,3Jr,2- = 4.45 Hz), 5.32 (d, 1H, OH), 3.83 - 3.74 (m, 1H, H3'), 3.72-3.64 (m, 4H, H4\ H5'), 2.24 -2.12 (m, 2H, H2'), 0.91 (s, 9H, H3-TBDMS), 0.17 (s, 6H, Hl-TBDMS) ppm.13C NMR (DMSO-d6, 100MHz) δ: 162.82 (C4), 158.75 152.26 (C2), 140.18 (C6), 109.37 (C5), 86.49 (CI '), 84.24 (C4'), 73.37 (C3'), 64.47 (C5'), 39.52 (C2'), 29.06 (C3-TBDMS), 25.11 (C2-TBDMS), -5.02 (Cl-TBDMS) ppm.
70%
Stage #1: With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere
Stage #2: at 0 - 20℃; for 12 h; Inert atmosphere
Commercially available 5-iodo-2'-deoxyuridine 8 (1 g, 2.82 mmol) was dissolved in dry DMF (12 mL) at RT under N2. To this clear solution, imidazole (576 mg, 8.47 mmol, 3 eq.) was added. After cooling this solution down to 0°C, TBDMSCl (468 mg, 3.1 mmol, 1.1 eq.) was added in one portion. The reaction mixture was allowed to warm to RT and stirred overnight. Upon completion of the reaction (as monitored by TLC), the DMF was removed under reduced pressure. The crude mixture was extracted with EtOAc (3 x 50 mL) and NaHCO3. The organic phases were combined, dried over MgSO4, concentrated and purified by flash chromatography (DCM/ 5percent MeOH) to yield 923 mg of compound 9 as a white solid (70 percent). HRMS (ESI) for C15H26IN2O5Si+ m/z calcd: 469.0650; found: 469.07679. 1H NMR (400.13 MHz, MeOD): 0.18 (6H, d, J = 10.80 Hz), 0.96 (9H, d, J = 5.72 Hz), 2.08-2.36 (2H, m,), 3.31 (2H, m), 3.88 (2H, m,), 4.01 (1H, dd, J = 5.02, 2.54 Hz), 4.36 (1H, td, J = 2.42, 5.48 Hz), 6.21 (1H, q, J = 4.56 Hz), 8.17 (1H, s). 13C NMR (100.62 MHz, MeOD): -6.5, -6.3, 18.0, 25.3, 40.9, 63.3, 67.3, 71.5, 86.0, 88.0, 144.7, 150.5, 161.3.
69% With 1H-imidazole; dmap In N,N-dimethyl-formamide for 0.666667 h; Cooling with ice [0131] To an ice-cold solution of 2’—deoxy--S-iodouridine (1.00 g, 2.82 mmcl), imidazole (0.58 g, 8.47 mmcl), and 4-(dimethylamino)pyridine (34.5 mg, 0.28 mmnol) in anhydrous DMF (13 mL) was added tert-butyldimethylsilyl chloride (0.51 g, 3.39 mmcl) portionwise and the mixture was stirred for 40 minutes before allowing it to warm slowly to room temperature overnight. The resulting mixture was quenched with saturated aqueous ammomiium chloride solution (50 mnL) and diluted with ethyl acetate (40 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2 x 40 mL). The combined organic extracts were washed with water (5 x 60 rnL) and saturated brine (60 mL), dried over MgSO4, and concentrated to give a colorless oil. This residual material was purified using a Biotage solera automated chromatography system under normal phase conditions (silica column, gradient of 10percent to 80 percent ethyl acetate in dichloromethane) with detection at 254 nm to give 5’-O-(teft-butyldimethylsilyl)-2’-deoxy-5-iodouridine (0.91 g, 69 percent), as a white solid. A 0.29 (dichloromethane - ethyl acetate, 6:4, v/v)

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  • [ 69739-34-0 ]
  • [ 54-42-2 ]
  • [ 134218-81-8 ]
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