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HazMat fee
Excepted Quantity
Free
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Structure of 40615-36-9 * Storage: {[proInfo.prStorage]}
Reference：
[1] Tetrahedron Letters, 1992, vol. 33, # 48, p. 7319 - 7323
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 3, p. 370 - 371
[3] Liebigs Annalen der Chemie, 1982, # 7, p. 1398 - 1402
[4] Helvetica Chimica Acta, 1982, vol. 65, # 8, p. 2372 - 2393
[5] Nucleosides and Nucleotides, 1997, vol. 16, # 5-6, p. 815 - 820
[6] Nucleosides, Nucleotides and Nucleic Acids, 2004, vol. 23, # 11, p. 1683 - 1705
2
[ 40615-36-9 ]
[ 64325-78-6 ]
Reference：
[1] Journal of the American Chemical Society, 1982, vol. 104, # 5, p. 1316 - 1319
3
[ 40615-36-9 ]
[ 4546-72-9 ]
[ 64325-78-6 ]
Reference：
[1] Patent: EP1253154, 2002, A1, . Location in patent: Example 2
4
[ 951-78-0 ]
[ 40615-36-9 ]
[ 23669-79-6 ]
Yield
Reaction Conditions
Operation in experiment
43 g
at 25℃; for 12 h;
To a solution of 308-1 (22.80 g, 99.91 mmol) in anhydrous pyridine (200 mE) was added DMTC1 (37.24 g, 109.90 mmol), and the mixture stirred at 25° C. for 12 h. The reaction was quenched with a sat. NH4C1 solution (200 mE), and extracted with EA (3x200 mE). The combined organic layers were washed with brine (2x 100 mE), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (PE:EA2: 1 to 0:1) to give the desired product (43.00 g, 72.94 mmol) as a yellow foam.
Reference：
[1] Bioorganic and Medicinal Chemistry, 1996, vol. 4, # 10, p. 1649 - 1658
[2] Organic letters, 2003, vol. 5, # 6, p. 917 - 919
[3] Journal of the American Chemical Society, 2001, vol. 123, # 15, p. 3405 - 3411
[4] Chemical Research in Toxicology, 2006, vol. 19, # 7, p. 968 - 976
[5] Nucleic Acids Research, 2015, vol. 43, # 11, p. 5275 - 5283
[6] Nucleosides, Nucleotides and Nucleic Acids, 2007, vol. 26, # 6-7, p. 709 - 712
[7] ChemMedChem, 2011, vol. 6, # 2, p. 309 - 320
[8] Tetrahedron Letters, 1992, vol. 33, # 1, p. 37 - 40
[9] Chemical & Pharmaceutical Bulletin, 1986, vol. 34, # 5, p. 2044 - 2048
[10] Tetrahedron Letters, 1994, vol. 35, # 29, p. 5221 - 5224
[11] Nucleosides and Nucleotides, 1995, vol. 14, # 3-5, p. 889 - 893
[12] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 14, p. 6824 - 6831
[13] Patent: US2009/264637, 2009, A1, . Location in patent: Page/Page column 29
[14] Bioconjugate Chemistry, 2012, vol. 23, # 3, p. 461 - 471
[15] Photochemical and Photobiological Sciences, 2013, vol. 12, # 8, p. 1366 - 1374
[16] Patent: US2015/366888, 2015, A1, . Location in patent: Paragraph 1309; 1310
[17] Patent: US2015/366887, 2015, A1, . Location in patent: Paragraph 1252-1253
5
[ 40615-36-9 ]
[ 23669-79-6 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 4, p. 1181 - 1184
6
[ 100-66-3 ]
[ 98-07-7 ]
[ 40615-36-9 ]
Yield
Reaction Conditions
Operation in experiment
85.13%
Stage #1: at 30℃; for 10 h; Large scale Stage #2: With hydrogenchloride In water at 30℃; for 3 h; Large scale Stage #3: for 6 h; Reflux; Large scale
a.In a 500 L reactor, 75 kg of trichlorotoluene (M = 195.48, n = 383.67 mol)And 103.72 kg of anisole (M = 108.14, n = 959.17 mol)53.35 kg of catalyst aluminum chloride (M = 133.34, n = 400.1 mol) were added,The reaction temperature was controlled at 30 ,Stirring reaction 10h,The mixed reaction liquid I was obtained.b.At 30 ° C,475kg 5percent diluted hydrochloric acid was added to the reaction mixture I was loaded with 1000L reactor,Hydrolysis reaction 3h,Add dichloromethane 200kg,Stir stand still stratification,The organic phase was separated dichloromethane,Then extracted with dichloromethane 200kg * 2 times the aqueous phase,The combined organic phases were extracted with dichloromethane,Dry with anhydrous sodium sulfate for 2h.c.The methylene chloride was concentrated,The solvent methylene chloride was recovered.Oxalyl chloride 70.74 kg (M = 126.93, n = 557.32 mol)In the reflux state reaction 6h,Dropping petroleum ether 130kg,Crystallization after cooling down to 30 ,After solid-liquid separation to get crude DMT-Cl.The crude HPLC purity was 98.91percent.d.Crude DMT-Cl added 4.5 times the mass of dichloromethane, 20 times the mass of petroleum ether for recrystallization,After the solid-liquid separation obtained DMT-Cl wet product,DMT-Cl wet product dried to obtain the finished DMT-Cl 110.66kg,Finished DMT-Cl purity of 99.95percentFinished DMT-Cl yield 85.13percent.The mixed solvent was recovered,Quantitative use of gas chromatography GC and then apply.
Reference：
[1] Patent: CN107056590, 2017, A, . Location in patent: Paragraph 0022; 0023; 0024; 0025; 0026; 0027; 0028-0045
7
[ 40615-35-8 ]
[ 40615-36-9 ]
Reference：
[1] Journal of Heterocyclic Chemistry, 1993, vol. 30, # 5, p. 1197 - 1207
[2] Organic Process Research and Development, 1998, vol. 2, # 6, p. 415 - 417
[3] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1989, p. 769 - 778
[4] Chemische Berichte, 1903, vol. 36, p. 2790
[5] Journal of the American Chemical Society, 1986, vol. 108, p. 3762
[6] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1995, vol. 34, # 7, p. 634 - 635
8
[ 611-94-9 ]
[ 40615-36-9 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1989, p. 769 - 778
9
[ 14039-15-7 ]
[ 40615-36-9 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1994, # 7, p. 1463 - 1466
10
[ 98-07-7 ]
[ 40615-36-9 ]
Reference：
[1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1995, vol. 34, # 7, p. 634 - 635
11
[ 40615-36-9 ]
[ 54925-71-2 ]
[ 81246-80-2 ]
Reference：
[1] Nucleosides, nucleotides and nucleic acids, 2003, vol. 22, # 5-8, p. 1007 - 1009
[2] Tetrahedron Letters, 2002, vol. 43, # 11, p. 1983 - 1985
[3] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 18, p. 6657 - 6665
An operation of dissolving 2’-Deoxy-2’-fluorouridine (3.00 g, 12.2 mmol) in dry pyridine, followed by concentrationunder reduced pressure was repeated 3 times to perform dehydrative azeotropic distillation. Thereafter, under an argonatmosphere, the reaction mixture was dissolved in dry pyridine (120 ml), 4,4’-dimethoxytrityl chloride (4.55 g, 13.4 mmol)was added, and the mixture was stirred at room temperature for 3 hr. The completion of the reaction was confirmed,and ethyl acetate (150 ml) and water (60 ml) were added to the reaction mixture to allow layer separation. The organiclayer was washed 3 times with 5percent aqueous sodium hydrogen carbonate solution (20 ml), washed with water (20 ml)and saturated brine (20 ml), and the obtained organic layer was dried over sodium sulfate. The solvent in the filtrate wasevaporated and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate = 50:50- 0/100(v/v), containing 1percent triethylamine). The object fractions were collected and concentrated to give the title compound(8.48 g, quant).
100%
at 20℃; for 3 h; Inert atmosphere
(1) Synthesis of 5'-O-(4,4'-dimethoxytrityl)-2'-deoxy-2'-fluorouridine An operation of dissolving 2'-Deoxy-2'-fluorouridine (3.00 g, 12.2 mmol) in dry pyridine, followed by concentration under reduced pressure was repeated 3 times to perform dehydrative azeotropic distillation. Thereafter, under an argon atmosphere, the reaction mixture was dissolved in dry pyridine (120 ml), 4,4'-dimethoxytrityl chloride (4.55 g, 13.4 mmol) was added, and the mixture was stirred at room temperature for 3 hr. The completion of the reaction was confirmed, and ethyl acetate (150 ml) and water (60 ml) were added to the reaction mixture to allow layer separation. The organic layer was washed 3 times with 5percent aqueous sodium hydrogen carbonate solution (20 ml), washed with water (20 ml) and saturated brine (20 ml), and the obtained organic layer was dried over sodium sulfate. The solvent in the filtrate was evaporated and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50-0/100 (v/v), containing 1percent triethylamine). The object fractions were collected and concentrated to give the title compound (8.48 g, quant).
100%
at 20℃; for 16 h;
A solution of 2’-deoxy-2’-fluorouridine (6g, 24.37 mmol) and 4,4'-(chloro(phenyl) methylene)-bis(methoxybenzene) (9.91 g, 29.2 mmol) in pyridine (48.7 ml) was stirred at rt for 16 hours. The mixture was treated with MeOH (20 mL), concentrated to dryness and was partitioned between water (50 mL) and EtOAc (250 mL). The aqueous phase was back extracted with EtOAc (50 mL) and the combined organic layers were washed with water (50 mL) and dried over Na2SO4. The solution was concentrated to give 2’-deoxy-2’-fluoro-5’- (4’,4’-dimethoxytrityl)uridine (14g, quant.) which was used without further purification.
100%
at 20℃; for 16 h;
A solution of 2'-deoxy-2'-fluorouridine (6g, 24.37 mmol) and 4,4'-(chloro(phenyl) methylene)-bis(methoxybenzene) (9.91 g, 29.2 mmol) in pyridine (48.7 ml) was stirred at rt for 16 hours. The mixture was treated with MeOH (20 mL), concentrated to dryness and was partitioned between water (50 mL) and EtOAc (250 mL). The aqueous phase was back extracted with EtOAc (50 mL) and the combined organic layers were washed with water (50 mL) and dried over Na2S04 The solution was concentrated to give 2'-deoxy-2'- fluoro-5'-(4',4'-dimethoxytrityl)uridine (14g, quant.) which was used without further purification.
A solution of 2'-deoxy-2'-fluorouridine (6g, 24.37 mmol) and 4,4'-(chloro(phenyl) methylene)-bis(methoxybenzene) (9.91 g, 29.2 mmol) in pyridine (48.7 ml) was stirred at rt for 16 hours. The mixture was treated with MeOH (20 mL), concentrated to dryness and was partitioned between water (50 mL) and EtOAc (250 mL). The aqueous phase was back extracted with EtOAc (50 mL) and the combined organic layers were washed with water (50 mL) and dried over Na2S04. The solution was concentrated to give 2'-deoxy-2'-fluoro-5'-(4',4'- dimethoxytrityl)uridine (14g, quant.) which was used without further purification.
Compound 129 (570 g, 1.53 mol, 1 wt, 1 vol, 1 eq) was dissolved in pyridine (2.85 L, 35.2 mol, 4.89 wt, 5.0 vols, 23 eq). The mixture was cooled to 2.6 °C and treated with 4,4’- dimethoxytrityl chloride (DMTC1; 543 g, 1.60 mol, 0.953 wt, 1.05 eq). The mixture was stirred at 0 to 5 °C for 2 h and then allowed to warm to ambient temperature. The reaction was monitored by LC/MS and complete conversion was confirmed after overnight stirring. The reaction mixture was cooled to below 5 °C and quenched by treatment with MeOH (124 ml, 3.05 mol, 0.172 wt, 0.217 vol, 2.0 eq) for 15 minutes. The mixture was co-evaporated with toluene (2.00 L, 3.04 wt, 3.51 vol) under vacuum and then diluted with a mixture of EtOAc (2.850 L, 4.5 wt, 5.0 vol) and n-heptane (2.85 L, 3.42 wt, 5.0 vol). The organic layer was washed with saturated NaHCO3 (9 wtpercent solution in water; 2.0 L, 3.5 vol). An additional EtOAc (2.85 L, 4.5 wt, 5.0 vol) was added to completely dissolve the crude product. After stirred for 5 minutes, the two layers were separated. The organic layer was washed with water (2.0 L,3.5 wt, 3.5 vol). Solid began slowly precipitating out of the organic layer. The water layer was separated. The organic layer was then concentrated to approx. 1 vol. The crude product was slurried with a mixture of n-heptane (2.00 L, 2.40 wt, 3.51 vol) and toluene (0.50 L, 0.76 wt, 0.88 vol). After stirring for 15 minutes, the pale yellow solid was collected by vacuum filtration. The filter cake was sequentially rinsed with: (1) a mixture of n-heptane (0.60 L, 0.72 wt, 1.05 vol) and toluene (0.30 L, 0.46 wt, 0.53 vol), and then (2) n-heptane (3.00 L,3.6 wt, 5.26 vol). The solid was dried with no heat for 30 minutes and then transferred to trays for drying at 50 °C in a vacuum oven overnight to give Compound 130 as pale yelllow solid (996.7 g, 1.47 mol, 1.75 wt, 97percent yield).‘H NMR (400 IVIFIz, CHLOROFORM-d) = 8.99 (s, 1H), 8.76 (s, 1H), 8.21 (s, 1H), 8.04 - 8.00 (m, 2H), 7.64 - 7.59 (m, 1H), 7.57 - 7.50 (m, 2H), 7.41 - 7.36 (m, 2H), 7.32 - 7.15 (m, 7H), 6.83 - 6.76 (m, 4H), 6.31 (dd, J= 2.5, 17.0 Hz, 1H), 5.68 (ddd, J 2.3, 4.7, 52.7 Hz, 1H), 4.88 -4.77 (m, 1H), 4.26 -4.21 (m, 1H), 3.77 (s, 6H), 3.57 (dd, J 3.1, 10.9 Hz, 1H),3.43 (dd, J= 4.1, 10.7 Hz, 1H), 2.60 (br s, 1H)
84%
at 20℃; for 16 h;
To a solution of N- (9-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl) tetrahydrofuran-2-yl)-9H-purin-6-yl)- benzamide (35 g, 93.7 mmol) in pyridine (180 mL) was added DMTrCI (38.12 g, 1 12.5 mmol, 1.2 eq) and the resulting mixture was stirred at RT for 16 h. The mixture was then diluted with CH2CI2 (800 mL), washed with sat NaHC03 (2x 400 mL) and brine (400 mL). The organic layer was dried over anhydrous Na2S04, filtered and concentrated under reduced pressure. The residue was purified by S1O2 gel chromatography (petroleum ether / EtOAc=10/l to 1/4) to give the title compound as a white solid (53.0 g, 78.4 mmol, 84percent). [0291] 1H-NMR (400 MHz, DMSO-de) δ ppm 11.26 (br s, 1H), 8.74 (s, 1H), 8.62 (s, 1H), 8.05 (d, J=7.4 Hz, 2H), 7.60 - 7.72 (m, 1H), 7.48 - 7.58 (m, 2H), 7.32 (d, J=7.2 Hz, 2H), 7.14 - 7.24 (m, 7H), 6.80 (dd, J=6.2, 8.7 Hz, 4H), 6.43 (d, J=20.0 Hz, 1H), 5.73 - 5.85 (m, 1H), 5.61 (d, J=4.4 Hz, 1H), 4.76 - 4.99 (m, 1H), 4.14 (br d, J=5.4 Hz, 1H), 3.64 - 3.79 (m, 7H), 3.19 - 3.33 (m, 2H).
31.2 g
at 20℃; for 3 h;
To a solution of compound 8b (30 g, 80.35 mmol) in pyridine (250 mL) was added4,4’-dimethoxytrityl chloride (54.45 g,160.71 mmol). After stirring at rt for 3 h, EtOAc (1L) was added and the mixture was filtered. The organic layer was successively washed with brine (300 mL x 3), dried over anhydrous Na2SO4, filtered, and the filtrate concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (MeOH in DCM = 0percent to 5percent) to give compound 8c (31.2 g) as a white solid. ESI-MS: m/z 676.3 [M + H] .
Acetic acid (2R,3R,4R,5R)-4-acetoxy-5-acetoxymethyl-2-(6-[bis-(4-methoxy-phenyl)-phenyl-methyl]-amino}-purin-9-yl)-tetrahydro-furan-3-yl ester[ No CAS ]
To a 50 L glass reactor equipped with air stirrer and Ar gas line was added thymidine (1.00 kg, 4.13 mol) in anhydrous pyridine (6 L) at ambient temperature. Dimethoxytrityl (DMT) chloride (1.47 kg, 4.34 mol, 1.05 eq) was added as a solid in four portions over 1 h. After 30 min, TLC indicated approx. 95% product, 2% thymidine, 5% DMT reagent and by-products and 2% 3',5'-bis DMT product (Rf in EtOAc 0.45, 0.05, 0.98, 0.95 respectively). Saturated sodium bicarbonate (4 L) and CH2Cl2 were added with stirring (pH of the aqueous layer 7.5). An additional 18 L of water was added, the mixture was stirred, the phases were separated, and the organic layer was transferred to a second 50 L vessel. The aqueous layer was extracted with additional CH2Cl2 (2×2 L). The combined organic layer was washed with water (10 L) and then concentrated in a rotary evaporator to approx. 3.6 kg total weight. This was redissolved in CH2Cl2 (3.5 L), added to the reactor followed by water (6 L) and hexanes (13 L). The mixture was vigorously stirred and seeded to give a fine white suspended solid starting at the interface. After stirring for 1 h, the suspension was removed by suction through a ½ diameter teflon tube into a 20 L suction flask, poured onto a 25 cm Coors Buchner funnel, washed with water (2×3 L) and a mixture of hexanes-CH2Cl2 (4:1, 2×3 L) and allowed to air dry overnight in pans (1 deep). This was further dried in a vacuum oven (75 C., 0.1 mm Hg, 48 h) to a constant weight of 2072 g (93%) of a white solid, (mp 122-124 C.). TLC indicated a trace contamination of the bis DMT product. NMR spectroscopy also indicated that 1-2 mole percent pyridine and about 5 mole percent of hexanes was still present.
93%
With pyridine; at 20℃; for 1.5h;
To a 50 L glass reactor equipped with air stirrer and Ar gas line was added thymidine (1.00 kg, 4.13 mol) in anhydrous pyridine (6 L) at ambient temperature. Dimethoxytrityl (DMT) chloride (1.47 kg, 4.34 mol, 1.05 eq) was added as a solid in four portions over 1 h. After 30 min, TLC indicated approx. 95% product, 2% thymidine, 5% DMT reagent and by-products and 2% 3',5'-bis DMT product (Rf in EtOAc 0.45, 0.05, 0.98, 0.95 respectively). Saturated sodium bicarbonate (4 L) and CH2Cl2 were added with stirring (pH of the aqueous layer 7.5). An additional 18 L of water was added, the mixture was stirred, the phases were separated, and the organic layer was transferred to a second 50 L vessel. The aqueous layer was extracted with additional CH2Cl2 (2x2 L) The combined organic layer was washed with water (10 L) and then concentrated in a rotary evaporator to approx. 3.6 kg total weight. This was redissolved in CH2Cl2 (3.5 L), added to the reactor followed by water (6 L) and hexanes (13 L). The mixture was vigorously stirred and seeded to give a fine white suspended solid starting at the interface. After stirring for 1 h, the suspension was removed by suction through a 1/2" diameter teflon tube into a 20 L suction flask, poured onto a 25 cm Coors Buchner funnel, washed with water (2x3 L) and a mixture of hexanes-CH2Cl2 (4:1, 2x3 L) and allowed to air dry overnight in pans (1" deep). This was further dried in a vacuum oven (75 C., 0.1 mm Hg, 48 h) to a constant weight of 2072 g (93%) of a white solid, (mp 122-124 C.). TLC indicated a trace contamination of the bis DMT product. NMR spectroscopy also indicated that 1-2 mole percent pyridine and about 5 mole percent of hexanes was still present.
5'-O-Dimethoxytriphenylmethyl-2'-O-methyl-5-methyluridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In pyridine; methanol; dichloromethane; acetonitrile;
ii. 5'-O-Dimethoxytriphenylmethyl-<strong>[55486-09-4]2'-O-methyl-5-methyluridine</strong> Crude 2'-O-methyl-5-methyl uridine (12 g) was coevaporated in pyridine (2*50 mL) and dissolved in dry pyridine (50 mL). Dimethoxytriphenylmethyl chloride (18.1 g, 0.054 mol) was added. the flask was stoppered and allowed to stand for 45 min at room temperature. Methanol (10 mL) was added to quench the reaction and the solution was concentrated under reduced pressure to an oil. The residue was partitioned between ethyl acetate (2*400 mL) and saturated sodium bicarbonate solution (500 mL). The organic layers were combined, dried (sodium sulfate), filtered and concentrated to a yellow foam. The foam was dissolved in methylene chloride (60 mL) and put onto a silica gel column (300 g) and eluted with ethyl acetate-hexanes-triethylamine, 60:40:1. The product containing fractions were combined, concentrated and coevaporated with dry acetonitrile (2*50 mL). The resulting residue was dried at 1 mm Hg for 24 h to a crisp white foam, 17.0 g (60.4% in three steps from 5-methyluridine).
In pyridine; methanol; dichloromethane; acetonitrile;
EXAMPLE 21 5'-O-Dimethoxytriphenylmethyl-<strong>[55486-09-4]2'-O-methyl-5-methyluridine</strong> Crude 2'-O-methyl-5-methyl uridine (12 g) was coevaporated in pyridine (2*50 mL) and dissolved in dry pyridine (50 mL). Dimethoxytriphenylmethyl chloride (18.1 g, 0.054 mol) was added the flask was stoppered and allowed to stand for 45 min at room temperature. Methanol (10 mL) was added to quench the reaction and the solution was concentrated under reduced pressure to an oil. The residue was partitioned between ethyl acetate (2*400 mL) and saturated sodium bicarbonate solution (500 mL). The organic layers were combined, dried (sodium sulfate), filtered and concentrated to a yellow foam. The foam was dissolved in methylene chloride (60 mL) and put onto a silica gel column (300 g) and eluted with ethyl acetate-hexanes-triethylamine, 60:40:1. The product containing fractions were combined, concentrated and coevaporated with dry acetonitrile (2*50 mL). The resulting residue was dried at 1 mm Hg for 24 h to a crisp white foam, 17.0 g (60.4% in three steps from 5-methyluridine).
In pyridine; methanol; dichloromethane; acetonitrile;
EXAMPLE 21 5'-O-Dimethoxytriphenylmethyl-<strong>[55486-09-4]2'-O-methyl-5-methyluridine</strong> Crude 2'-O-methyl-5-methyl uridine (12 g) was coevaporated in pyridine (2*50 mL) and dissolved in dry pyridine (50 mL). Dimethoxytriphenylmethyl chloride (18.1 g, 0.054 mol) was added. the flask was stoppered and allowed to stand for 45 min at room temperature. Methanol (10 mL) was added to quench the reaction and the solution was concentrated under reduced pressure to an oil. The residue was partitioned between ethyl acetate (2*400 mL) and saturated sodium bicarbonate solution (500 mL). The organic layers were combined, dried (sodium sulfate), filtered and concentrated to a yellow foam. The foam was dissolved in methylene chloride (60 mL) and put onto a silica gel column (300 g) and eluted with ethyl acetate-hexanes-triethylamine, 60:40:1. The product containing fractions were combined, concentrated and coevaporated with dry acetonitrile (2*50 mL). The resulting residue was dried at 1 mm Hg for 24 h to a crisp white foam, 17.0 g (60.4% in three steps from 5-methyluridine).
3-Dimethylamino-l,2-propanediol (6.0 g, 50 mmol) was weighed into a 1 L round bottomed flask with a stir bar. The flask was sealed, flushed with argon, charged with pyridine and cooled to 0 0C. 4,4'-Dimethoxytrityl chloride (17.9 g, 1.05 equiv.) was weighed into a 100 mL round bottomed flask, sealed and then dissolved in pyridine (80 mL). The 4,4'- dimethoxytrityl chloride solution was transferred to the stirring reaction mixture slowly, using additional fresh pyridine (20 mL) to effect the transfer of residual 4,4'-dimethoxytrityl chloride. The reaction was allowed to come to room temperature while stirring overnight. The reaction was concentrated in vacuo and re-dissolved in dichloromethane (300 mL). The organic phase was washed with saturated bicarbonate (2 x 200 mL) and brine (I x 200 mL), dried over MgSO4, filtered, concentrated and dried under high vacuum to afford 22.19g of a yellow gum that was used without further purification.
To a solution of Lambda^-acetylcytidine (65.0 g, 0.228 mol) in anhydrous pyridine (60OmL) cooled in an ice bath, DMTrCl (84.7 g, 0.251 mol) was added. The reaction mixture was stirred at room temperature overnight. To the reaction mixture cooled with an ice bath, THF (600 ml) and AgNO3 (58.1 g, 0.342 mmol) were added. Then TBSCl (51.5 g, 0.342 mmol) was added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was filtered, solvent was removed under vacuum to give a residue which was diluted with EtOAc (500 mL) and washed with water (200 ml) and brine (200 ml). The organic layer was separated and dried over anhydrous Na2SO4 and the filtrate was concentrated to a syrup which was purified by chromatography on silica gel (eluted with PE : EA = 5:1 to 3 : 1) to give N4-acetyl-2'-O-(t-butyldimethylsilyl)-5'-O- (4,4'-dimethoxytrityl)cytidine as yellow solid (80 g, 50percent). 1H NMR (CDCl3) delta 8.39 (d, J = 7.6 Hz, IH), 7.34 (dd, Jl = 1.6 Hz, J2 = 8.4 Hz, 2H), 7.21 - 7.27 (m, 6H), 7.02 (d, J = 7.2 Hz, IH), 6.80 (dd, Jl = 2.0 Hz, J2 = 6.8 Hz, 4H), 5.82 (d, J = 1.2 Hz, IH), 4.26 - 4.32 (m, IH), 4.20 (dd, Jl = 1.2 Hz, J2 = 4.4 Hz, IH), 4.00 - 4.02 (m, IH), 3.74 (d, J = 1.6 Hz, 6 H), 3.43 - 3.53 (m, 2H), 2.32 (d, J = 9.6 Hz, IH), 2.18 (s, 3H), 0.86 (s, 9H), 0.22 (s, 3H), 0.11 (s, 3H).
1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(((3-methoxyphenyl)(4-methoxyphenyl)(phenyl)methoxy)methyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
With pyridine; at 0 - 25℃;
To a cooled (0 °C) solution of the compound 16 (3.0 g, 13.2 mmol) in pyridine (33 mL) was added 4,4'-dimethoxytriphenylmethyl chloride (DMTCl) (5.6 g, 16.5 mmol) and the reaction mixture was stirred at 25 °C for 50 min. After evaporated under reduced pressure, the residue was purified by silica gel column chromatography (DCM : MeOH = 20 : 1) to give the compound 17 (4.4 g, 63percent) as a white solid. 1HNMR (400 MHz, CDC13) delta 8.63 (dd, J= 4.4, 3.2 Hz, 1H), 8.40 (dd, 7 = 5.6, 2.4 Hz, 1H), 7.63-7.16 (m, 9H), 6.84-6.81 (m, 4H), 6.14 (dd, J = 6.8, 4.0 Hz, 1H), 5.87 (d, J= 3.2 Hz, 1H), 4.43-4.39 (m, 3H), 3.80 (s, 6H), 3.51-3.41 (m, 2H).
1-((2R,3R,4R,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-3,4-bis((tert-butyldimethylsilyl)oxy)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one[ No CAS ]
0.5 g (0.57 mmol) of fine diosgenin, 0.77 g (1.70 mmol) of DMT-Cl was dissolved in 10 mL of pyridine, reacted at room temperature overnight, and TCL showed the end of the reaction. The reaction solution was concentrated under reduced pressure, and water was added to precipitate a white solid which was filtered through a silica gel column, trichloromethane / methanol 30: 1 and the eluent was concentrated to give 0.12 g of a white solid.
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