Name: 50-91-9|5-Fluoro-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione|98%
Brand: Ambeed
SKU: A230277
Price: 8.0 USD
Availability: InStock
Rating: 91 (30 reviews)

1
[ 1582-79-2 ]
[ 50-91-9 ]

Yield	Reaction Conditions	Operation in experiment
86.2%	With methanol; ammonia; at 10 - 25℃;	To a solution of methanolic ammonia (10-12% w/w; 500 mL, 10 v/w) at 10 C was added 3',5'-di-0-(4-chlorobenzoyl)-5-fluoro-2'-beta-deoxyuridine 3 (50 g, 0.0955 mole). The reaction mixture was raised to 25 C over 1-2 h and maintained at this temperature for 20-24 h. When the reaction was complete, as determined by HPLC, it was filtered through Celite at 25 C. The Celite was washed with MeOH (100 mL, 2 v/w) and the combined filtrate was concentrated to between 50-100 mL under vacuum (600 mmHg, Output: Wt. of the compound FUDR: 20.2 g Yield: 86.2% (HPLC Purity: 99.94% Characterisation data for FUDR is consistent with that which has been previously reported, e.g. in Aoyama et al. (Bull. Chem. Soc. Jpn., 1987, 60, 2073-2077).

Reference： [1]Patent: WO2019/53476,2019,A1 .Location in patent: Page/Page column 33-34
[2]Bulletin of the Chemical Society of Japan,1987,vol. 60,p. 2073 - 2077
[3]Patent: US2949451,1959,

2
[ 63-89-8 ]
[ 50-91-9 ]
[ 116539-52-7 ]

Yield	Reaction Conditions	Operation in experiment
	With acetate buffer; Diaion WK-20 resin <Na(1+) form>; calcium chloride 1.) H₂O, CHCl₃, 45 deg C, 6 h, pH 6.0, 2.) CHCl₃, MeOH, H₂O; Yield given. Multistep reaction;

Reference： [1]Shuto; Itoh; Ueda; Imamura; Fukukawa; Tsujino; Matsuda; Ueda [Chemical and Pharmaceutical Bulletin, 1988, vol. 36, # 1, p. 209 - 217]

3
[ 40615-36-9 ]
[ 50-91-9 ]
[ 104495-48-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With pyridine; at 20℃;Inert atmosphere;	5-Fluoro-2-deoxyuridine (5-FdU, 2.19 g, 9.0 mmol) was coevaporated two times with anhydrous pyridine and next dissolved in pyridine (20 mL). The resulting solution was chilled, followed by addition of the 4,4-dimethoxytrityl chloride (1.05 eq, 3.16 g, 9.34 mmol). The mixture was being stirred at room temperature for 3 h under N2 atmosphere and left at low temperature overnight. After that methanol was added and the mixture was evaporated to dryness. The residue oil was purified with silica gel column chromatography, using chloroform- methanol (2?5%) as an eluent to obtain pure 7 (white solid, yield: 4.48 g, 92%). 1H NMR (DMSO-d6) delta: 2.14-2.18 (ddd, 1H, H-2 alpha, 3JH2 H1 = 5.30 Hz, 3JH2 H3 = 4.20 Hz, 2JH2H2 = 13.9 Hz), 2.22-2.27 (m, 1H, H-2 beta, 3JH2H1 = 6.50 Hz, 3JH2H3 = 6.70 Hz, 2JH2H2 = 13.6 Hz), 3.12-3.15 (dd, 1H, H 5, 3JH5H4 = 5.40 Hz, 2JH5H5 = 10.6 Hz), 3.24-3.27 (dd, 1H, H5, 3JH5 H4 = 2.90 Hz, 2JH5H5 = 10.6 Hz), 3.73 (s, 6H, 2× CH3O), 3.87-3.89 (m, 1H, H-4, 3JH4H5 = 5.40 Hz, 3JH4H5 = 2.90, 3JH4H3 = 2.00 Hz), 4.25-4.29 (m, 1H, H-3, 3JH3H2 = 6.70, 3JH3H2 = 4.20, 3JH3H4 = 2.00 Hz), 5.33 (d, 1H, 3- OH, 3JHH = 4.65 Hz), 6.12-6.15 (m, 1H, H-1, 3JH1H2 = 6.50 Hz, 3JH1H2 = 5.30 Hz), 6.87-6.89 (dd, 4H, meta in 4-MeOC6H4-), 7.22-7.32 (m, 7H, DMTr), 7.38, 7.39 (2× brs, 2H, DMTr), 7.88 (d, 1H, H-6, 3JHF = 6.8), 11.85 (brs, 1H, NH). 13C NMR delta: 39.30 (C-2), 55.04, 55.02 (2× CH3OC5H4), 63.65 (C-5), 70.05 (C-3), 84.53 (C-1), 85.58 (C-4), 85.82 (CPh3), 113.2 (C meta in 4-MeOC6H4-), 124.5 (d, C-6, 2JCF = 33.8), 127.6, 127.9 (C ortho in 4-MeOC6H4-), 135.3, 135.5 (C- 1 in 4-MeOC6H4-), 140.0 (d, C-5, 1JCF = 231.5), 144.8 (C in C6H5), 148.9 (C-2), 157.1 (d, C-4, 2JCF = 26.0), 158.11, 158.13 (C para in 4-MeOC6H4-). 15N NMR delta: 136.0 (N-1), 157.9 (N-3). 19F NMR delta: -91.41 (3JFH = 6.8).
80%	With pyridine; at 20℃; for 4h;	First, 4,4-bismethoxytrityl chloride (DMT-Cl) (1.860 g, 5.5 mmol) and deoxyfluorouridine (1.231 g, 5 mmol) were weighed, and 50 mL of anhydrous pyridine was added thereto, and the mixture was stirred uniformly. The reaction was stirred at room temperature for 4 h. Then 5 mL of methanol was added and the reaction was continued for 30 min. The solvent was removed by rotary distillation under reduced pressure, and the product was separated by column chromatography.A white powder (Compound 2) was obtained in a yield of 80%.
65%	With pyridine;	<strong>[50-91-9]5-Fluoro-2'-deoxyuridine</strong> (FdU) (3.2 mmol) was reacted with dimethoxytrityl chloride (4.4 mmol) in dry pyridine. The solution was stirred overnight and the solvent was evaporated. The residue was purified by column chromatography using a gradient from pure CH2C12 to 10% methanol in CH2C12 to afford the desired dimethoxytrityl-5- fluoro-2'-deoxyuridine (DMT-FdU) in 65%.

18 g

With pyridine; at 20℃; for 16h;

To an anhydrous 5-fluoro-2?-deoxyuridine (10 g, 40.6 mmol, 1.0 eq) solution in 9 pyridine (70 mL) was added DMTrCl (15 g, 44.7 mmol, 1.1 eq) and the reaction mixture was stirred at 20 C. for 16 h monitored by TLC (DCM/MeOH=10/1, Rf=0.50). The reaction was quenched by MeOH (30 mL and then concentrated under reduced pressure. The residue was extracted with EtOAc and the combined organic layers were washed with saturated NaHCO3 (300 mL) and brine (200 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a crude mixture. Silica gel column chromatography (petroleum ether/ethyl acetate=5/1, DCM/MeOH=40/1, 30/1) provided dimethoxytrityl alkylated product as a white solid (18 g, 33 mmol). 1H-NMR (400 MHz, DMSO-d6) 7.86 (d, J=6.8, 1H), 7.40-7.35 (m, 2H), 7.32-7.18 (m, 7H), 6.87 (d, J=8.2, 4H), 6.15-6.10 (m, 1H), 5.73 (s, 1H), 4.29-4.22 (m, 1H), 3.91-3.83 (m, 1H), 3.72 (s, 6H), 3.25 (dd, J=5.6, 10.4, 1H), 3.13 (dd, J=2.8, 10.4, 1H), 2.29-2.10 (m, 2H).

Reference： [1]Tetrahedron,1990,vol. 46,p. 487 - 502
[2]Nucleosides, nucleotides and nucleic acids,2016,vol. 35,p. 178 - 194
[3]Nucleosides and nucleotides,2002,vol. 21,p. 79 - 92
[4]Angewandte Chemie - International Edition,2017,vol. 56,p. 12528 - 12532
Angew. Chem.,2017,vol. 129,p. 12702 - 12706,5
[5]Patent: CN109224080,2019,A .Location in patent: Paragraph 0080-0082; 0084
[6]Journal of Heterocyclic Chemistry,1992,vol. 29,p. 1143 - 1147
[7]Il Farmaco,1994,vol. 49,p. 793 - 797
[8]Patent: WO2019/12157,2019,A1 .Location in patent: Page/Page column 64-65
[9]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 2908 - 2911
[10]Nucleosides and Nucleotides,1995,vol. 14,p. 243 - 253
[11]Il Farmaco,1997,vol. 52,p. 71 - 81
[12]Bioconjugate Chemistry,2012,vol. 23,p. 461 - 471
[13]Journal of Medicinal Chemistry,2016,vol. 59,p. 3661 - 3670
[14]European Journal of Organic Chemistry,2017,vol. 2017,p. 3003 - 3008
[15]Angewandte Chemie - International Edition,2018,vol. 57,p. 8994 - 8997
Angew. Chem.,2018,vol. 130,p. 9132 - 9135,4
[16]Patent: US2019/100551,2019,A1 .Location in patent: Paragraph 0134
[17],2020,vol. 15,p. 885 - 900

4
[ 58066-85-6 ]
[ 50-91-9 ]
[ 86976-82-1 ]

Reference： [1]Chemical and pharmaceutical bulletin,1988,vol. 36,p. 5020 - 5023

5
[ 108-24-7 ]
[ 50-91-9 ]
[ 110522-47-9 ]

Yield	Reaction Conditions	Operation in experiment
97%	With pyridine; at 20℃; for 8h;	2'-Deoxy-5-fluorouridine (1a) (24.6 g, 0.1 mol) was dissolved in dry pyridine (200 ml) and acetic anhydride (47 ml, 0.5 mol) was added. The resulting solution was stirred under exclusion of moisture for 8 h at room temperature and subsequently concentrated until crystallisation occurred. The concentrate was co-evaporated with toluene (100 ml) and the resulting residue dissolved by heating (60 C) in ethanol (250 ml) followed by crystallization at 4-7 C. The precipitate was filtered, washed with cold ethanol and dried to yield 32.4 g (97%) of 2a; mp: 151 C; RF = 0.35 (CHCl3/MeOH, 95:5, v/v); MS (FAB+) 331. [M-H+]. Anal. Calcd C13FH15N2O7 (330.3): C, 47.28; H, 4.58; N, 8.48. Found: C, 47.43; H, 4.78; N, 8.20. 1H NMR (250 MHz, CDCl3): delta = 2.13 (s, 3H, -CH3), 2.15 (s, 3H, -CH3), 2.16-2.25 (m, 1H, H2'alpha), 2.55 (ddd, 1H, J1 = 2.3 Hz, J2 = 5.7 Hz, J3 = 14.3 Hz, H2'beta), 4.28 (m, 1H, H4'), 4.32 (dd, 1H, J1 = 3.1 Hz, J2 = 12.2 Hz, H5'beta), 4.41 (dd, 1H, J1 = 3.6 Hz, J2 = 12.1 Hz, H5'alpha), 5.24 (m, 1H, H3'), 6.31 (m, 1H, H1'), 7.7 (d, 1H, J = 6.2 Hz, H6). 13C NMR (62.9 MHz, CDCl3): delta = 20.8 (COCH3), 20.9 (COCH3), 37.8 (C2'), 63.8 (C5'), 73.9 (C3'), 82.5 (C4'), 85.4 (C1'), 123.2 (d, JCF = 34.5 Hz, C6), 139.7 and 142.1 (d, JCF = 238 Hz, C5), 149.2 (C2), 156.9 (d, JCF = 26.7 Hz, C4), 170.3 (CO), 170.5 (CO).
	With dmap; triethylamine; In dichloromethane; at -10 - 5℃;Large scale;	10 Kg (40.61 mol) of the above-mentioned biologically prepared 5-fluoro-deoxyuridine nucleoside was added100 L of anhydrous methylene chloride,Then 16.96 Kg (121.85 mol) of triethylamine was added,0.1 Kg 4-methylaminopyridine,Solid stirred suspension,System cooling bath cooling to -10-0 ,8.437 Kg (89.34 mol) of acetic anhydride was added dropwise with stirring,Control the internal temperature does not exceed 5 ,When the solid is fully dissolved,HPLC monitoring to the main raw material is complete.After the above reaction is complete,To the system drop into the 50L deionized water,Control the internal temperature does not exceed 5 ,After dripping,Separate the lower,The lower layer and then 50L water extraction once,Water phase abandoned,The lower layer was concentrated under reduced pressure at 40-45 C,To obtain a relatively pure 3 ', 5'-Di-Ac-5-fluoro-deoxyuridine nucleoside intermediate,HPLC purity 99.91%

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3520 - 3526
[2]Journal of Organic Chemistry,1992,vol. 57,p. 2989 - 2991
[3]Magnetic Resonance in Chemistry,2013,vol. 51,p. 523 - 529
[4]Patent: CN103897007,2017,B .Location in patent: Paragraph 0108; 0109; 0110; 0111; 0112; 0113; 0114

6
[ 76-83-5 ]
[ 50-91-9 ]
[ 4031-24-7 ]

Yield	Reaction Conditions	Operation in experiment
70%	With pyridine; at 50℃; for 18h;	In a 25ml round bottom flask an amount of 100mg (0.41mmol) of37was co-evaporated 3 times with 5mL of dry pyridine and dissolved in 3mL of dry pyridine. Trityl chloride (136mg, 0.49mmol) was added to the reaction mixture. The mixture was heated at 50C for 18h. After 18h, the mixture was cooled to room temperature, quenched with 3mL of MeOH and stirred for 30min. The mixture was evaporated to dryness. The obtained crude compound was purified by column chromatography to obtain 140mg (70%) of38. TLC (MeOH/CH2Cl2, 1:9):Rf=0.80.1H NMR (300MHz, CDCl3):delta8.70 (s, 1H), 7.82 (d, 1H), 7.46-7.43 (m, 6H), 7.37-7.28 (m, 11H), 6.32-6.28 (m, 1H, H-1?), 4.57-4.55 (m, 1H), 4.08-4.06 (m, 1H), 3.48-3.46 (m, 2H, H-5?/H-5?), 2.54-2.46 (m, 1H, H-2?/H-2?), 2.32-2.19 (m, 1H, H-2?/H-2?);13C NMR (75MHz, CDCl3):delta149.5, 148.5, 138.9, 128.5, 128.1, 127.5, 124.2, 123.8, 87.8, 86.1, 85.4, 71.7, 63.2, 41.1; HRMS (EI+): m/z for [C28H25FN2O5Na]+calcd. 511.1639; found 511.1638.
	In pyridine; water;	REFERENCE EXAMPLE 10 Preparation of 2'-deoxy-5'-O-trityl-5-fluorouridine (13) In 2.5 ml of pyridine were dissolved 0.25 g of 2'-deoxy-5-fluorouridine and 0.34 g of trityl chloride, and the solution was reacted at 60 C. for 4 hours under stirring. After completion of the reaction, the reaction mixture was poured into 80 ml of ice-cold water and precipitated crystals were collected by filtration.
	With pyridine; at 20℃; for 48h;	Preparation of 5'-O-Trityl 5-fluoro-2'-deoxyuridine (1). <strong>[50-91-9]5-Fluoro-2'-deoxyuridine</strong> (2 g, 8.8 mmol) was dissolved in 40 ml dry pyridine under 30 an atmosphere of nitrogen.. trityl chloride (3.6 g, 12.6 mmol) was added and the reaction mixture stirred at room temperature for 48 hours.. The reaction was quenched with methanol (20 ml), and then the mixture was concentrated to dryness under reduced pressure.. The compound was purified on silica gel (flash), using chloroform/methanol (97/3) as an eluent. 4.1 g of the product (1) was obtained as a colorless, crystalline solid. Yield-990%.

Reference： [1]Journal of Pharmaceutical Sciences,1985,vol. 74,p. 246 - 249
[2]Drug Development Research,2012,vol. 73,p. 73 - 81
[3]Journal of Medicinal Chemistry,2010,vol. 53,p. 4130 - 4140
[4]Chemical and Pharmaceutical Bulletin,1996,vol. 44,p. 150 - 155
[5]European Journal of Medicinal Chemistry,2014,vol. 76,p. 98 - 109
[6]ChemMedChem,2011,vol. 6,p. 309 - 320
[7]Steroids,1987,vol. 47,p. 413 - 420
[8]Journal of Medicinal Chemistry,1995,vol. 38,p. 2672 - 2680
[9]Patent: US5049551,1991,A
[10]Patent: US6774121,2004,B1 .Location in patent: Page/Page column 16-17
[11]Journal of Medicinal Chemistry,2010,vol. 53,p. 7156 - 7166

7
[ 84366-67-6 ]
[ 50-91-9 ]
[ 62-49-7 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
81%	In chloroform at 45℃; for 6h; 250 mM CaCl₂, 200 mM acetate buffer (pH 6.0);

Reference： [1]Shuto, Satoshi; Ueda, Shigeru; Imamura, Shigeyuki; Fukukawa, Kiyofumi; Matsuda, Akira; Ueda, Tohru [Tetrahedron Letters, 1987, vol. 28, # 2, p. 199 - 202]

8
[ 98-59-9 ]
[ 50-91-9 ]
[ 10054-41-8 ]

Yield	Reaction Conditions	Operation in experiment
Ca. 65%	With pyridine; at 0 - 5℃; for 48h;	In a round-bottomed flask fitted with a magnetic stirrer, 5-fluoro-2'-deoxyuridine (1.02 g, 4.15 320 mmol) and dry pyridine (41.50 mL) were placed. The flask was cooled to 0C on an ice bath. Subsequently, p-toluenesulphonic acid chloride (1.04 g; 5.4 mmol) was added to the solution stirred vigorously. The stirring was continued until the tosyl chloride dissolved. The reaction flask was left to stand in a refrigerator at 0-5C for 48 hours. When the reaction was completed, most pyridine was evaporated under reduced pressure, and any residual pyridine was removed by evaporating the crude product three times with toluene added (20 mL) under reduced pressure. The resulting crude product was purified on a chromatographic column with silica gel using a chloroform-methanol mixture ( 1 to 10 % v/v) as the eluent. 5'-O-Tosyl-2',5'-dideoxy-5-fluorouridine was obtained as white powder with a yield of approx. 65%.
	With pyridine; at 0 - 5℃; for 24h;Inert atmosphere; Cooling with ice;	General procedure: An appropriate nucleoside(5a-c; 4 mmol, 1 eq) was dissolved in anhydrous pyridine (Py, 40 mL)under argon atmosphere. After the substrate was dissolved, the flask with the solution was placed in an ice bath and cooled. Then tosyl chloride (1.3eq, Ts-Cl) was added and stirred until it was completely dissolved. The reaction flask was placed in a refrigerator for 24 hours and progress of the reaction was checked by the thin-layer chromatography (TLC) using chloroform - methanol (10:1, v/v) as a solvent system. The reaction mixture was quenched with methanol and then evaporated to dryness. The crude product was dissolved in chloroform and extracted with saturated aqueous solution of NaHCO3. The organic layer was evaporated to drynessand purified by silica gel column chromatography using methylene chloride- methanol (21015%) as an eluent to give pure products 6a-c (white solids, yield ca. 70%).
	With pyridine; for 48h;Cooling;	To an ice-cold stirred solution of thymidine (1.00 g, 4.13 mmol) in anhydrous pyridine (7 mL) was added p-toluenesulfonyl chloride (1.02g, 5.35 mmol), and the reaction mixture was left at 4C for 48 h. Methanol (2 mL) was then added and the mixture was stirred for 1 h at roomtemperature. Solvents were removed under reduced pressure and the residue was dissolved in DMF (10 mL). Then sodium azide (805 mg,12.37 mmol) was added, and the reaction mixture was heated at 90C with stirring for 5 h. Then, the mixture was evaporated to dryness. Theresidue was treated with saturated sodium bicarbonate (20 mL) and it was extracted with ethyl acetate (3 x 40 mL). The combined organicextracts were dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was dissolved in methanol andevaporated with silica gel (3 g). The crude product was purified by silica gel column chromatography using dichloromethane-methanol(gradient from 100:1 to 10:1, v/v) as eluent to afford 10 (yield: 860.3 mg, 78%).

Reference： [1]Patent: WO2015/41550,2015,A1 .Location in patent: Page/Page column 20; 21
[2]Journal of Medicinal Chemistry,1993,vol. 36,p. 1570 - 1579
[3]Journal of Heterocyclic Chemistry,1992,vol. 29,p. 1133 - 1142
[4]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 5764 - 5773
[5]Nucleosides, nucleotides and nucleic acids,2019,vol. 38,p. 218 - 235
[6]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 2587 - 2594

9
[ 50-91-9 ]
[ 20105-69-5 ]

Reference： [1]Journal of Medicinal Chemistry,1993,vol. 36,p. 1570 - 1579
[2]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 6785 - 6789

10
[ 2691-71-6 ]
[ 50-91-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In methanol; at 20 - 30℃;Large scale;	10Kg (22 mol) of the 3 ', 5'-di-Bz-5-fluorodeoxyuridine obtained by the above method was added to100 L of methanol,Then add 10L1N NaOH,System closed insulation 20-30 stirring reaction,After solid solution,HPLC monitoring to the main raw material is complete.After the reaction was complete, the system was adjusted to pH between 6 and 6 with 6N hydrochloric acid. The system was then concentrated under reduced pressure at 40-55 C and then heated to 70 C with 100 L of ethanol. The solid was dissolved by stirring, Insoluble material, and then 10-15 , heat crystallization 12 hours, centrifuged, that was 5 - fluoride - deoxyuridine, solid at 50-60 blast drying 12 hours after the powder, mix, HPLC purity of 99.99 %, MS (ESI) m / z (M + H) 246.15, HPLC consistent with standard control.

Reference： [1]Collection of Czechoslovak Chemical Communications,1980,vol. 45,p. 3217 - 3230
[2]Patent: CN103897007,2017,B .Location in patent: Paragraph 0154; 0155; 0156; 0157; 0158; 0159

11
[ 51-21-8 ]
[ 951-78-0 ]
[ 50-91-9 ]

Yield	Reaction Conditions	Operation in experiment
	With purine nucleoside phosphorylase; uridine phosphorylase; In aq. phosphate buffer; dimethyl sulfoxide; at 80℃; for 3h;Enzymatic reaction;	5-Fluoruracil nucleosides were prepared as previously described above. One ml catalyst (cell lysate) withtransglycosylation activity of about 12 units/ml cell lysate was added to 150 ml of a solution kept thermostatically at 80C and having the following composition:- 7.5mM uridine/2?-Deoxyuridine,- 2.5mM 5-fluorouracil, and- 30 mM potassium phosphate buffer, pH 7.[0091] After 3 hour at 80 C, the reaction mixture was filtered by centrifugation at 2000 3g for 30 min, at 4C, throughTable 4. Production yields of 2,6-Diaminopurine nucleosides at different temperatures without use organic co-solvents.Temperature (C) 80 90 100Biotransformation (%) 79.3 79.6 81.1Amicon ultra-4 Centrifugal Filter Devices (Millipore, Bedford, MA) with a 3000-Da cut-off, and the filtrate was recovered.The bioconversion yield of the reaction was higher than 50%. The resulting 5-fluoruracil nucleosides (5-fluorouridineand 5-fluoro-2?-deoxyuridine) were analyzed by HPLC.

Reference： [1]Collection of Czechoslovak Chemical Communications,1994,vol. 59,p. 2303 - 2330
[2]Patent: EP2516637,2016,B1 .Location in patent: Paragraph 0090-0091

12
[ 18162-48-6 ]
[ 50-91-9 ]
[ 129816-30-4 ]

Yield	Reaction Conditions	Operation in experiment
76%	With pyridine; 1H-imidazole; at 20℃; for 24h;Inert atmosphere;	<strong>[50-91-9]5-Fluoro-2'-deoxyuridine</strong> (5-FdU, 0.67 g, 2.73 mmol) and imidazole (3 eq, 0.56 g, 8.19 mmol) were dissolved in anhydrous pyridine (6.72 mL), and after that tertbutyldimethylsilylchloride (1.1 eq, 0.45 g, 3 mmol) was added. The reaction mixture was being stirred under N2 atmosphere overnight. The mixture was first evaporated to dryness and then evaporated twice with toluene. The organic layer was extracted with saturated aqueous sodium bicarbonate, then with methylene chloride and evaporated to dryness. The residue was purified with silica gel column chromatography, using methylene chloride-methanol (2?5?10%) as an eluent to give pure 5 (white solid, yield: 0.76 g, 76%). 1H NMR (DMSO-d6) delta: 0.08 (s, 6H, (CH3)2Si), 0.88 (s, 9H, (CH3)3), 2.05-2.11 (m, 1H, H-2 beta, 3JH2H1 = 6.60 Hz, 3JH2H3 = 6.20 Hz, 2JH2H2 = 13.4 Hz), 2.13-2.18 (ddd, 1H, H-2 alpha, 3JH2 H1 = 5.00 Hz, 3JH2 H3 = 3.60 Hz, 2JH2H2 = 13.4 Hz), 3.73-3.76 (dd, 1H, H-5, 3JH5H4 = 3.00 Hz, 2JH5H5 = 10.5 Hz), 3.81-3.84 (m, 2H, H-5, H-4, 3JH5 H4 = 2.3 Hz, 2JH5H5 =10.5Hz), 4.19-4.21 (m, 1H, H-3, 3JH3H2 =6.20Hz, 3JH3H2 =3.60Hz, 3JH3H4 = 3.55 Hz), 5.32 (d, 1H, 3-OH, 3JHH = 4.65 Hz), 6.10-6.13 (m, 1H, H- 1, 3JH1H2 = 6.60 Hz, 3JH1H2 = 5.00 Hz), 7.97 (d, 1H, H-6, 3JHF = 6.9), 12.00 (brs, 1H, NH). 13C NMR delta: -5.61 ((CH3)2Si), 18.01 (C(CH3)3), 25.73 (C(CH3)3), 39.10 (C-2, signal overlapped with DMSO), 62.95 (C-5), 69.98 (C-3), 84.64 (C- 1), 86.98 (C-4), 124.1 (d, C-6, 2JCF = 34.2), 139.9 (d, C-5, 1JCF = 230.4), 148.8 (C-2), 157.0 (d,C-4, 2JCF = 26.1). 19F NMR delta: -91.58 (3JFH = 7.0). 29Si NMR delta: 21.56.
	With triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 12h;	2'-deoxy-5-fluorouridine 2.6g was dissolved in 50mL of anhydrous N,N-dimethylformamide, 1.5g of triethylamine was added, and tert-butyldimethylsilyl chloride 3g was added at 0 C, 0 Stir at C for 1 hour, then raise to room temperature for 12 hours, add 30 mL of human water, and wash the organic phase with 10% dilute hydrochloric acid solution, saturated sodium bicarbonate solution and saturated sodium chloride solution, dry over anhydrous magnesium sulfate, filter, oil pump Vacuum distillation. Column chromatography gave 2'deoxy-5-fluoro-5'-TBDMS-uridine.0.37 g of 2'deoxy-5-fluoro-5'-TBDMS-uridine was dissolved in pyridine, and 0.2 g of adipic anhydride was added thereto, and a catalytic amount of DMAP was allowed to react at room temperature for 24 hours. The oil pump is distilled under reduced pressure, added with 1% dilute hydrochloric acid solution, centrifuged, and the supernatant is discarded. The precipitate is washed successively with 0.1% diluted hydrochloric acid solution, distilled water, and lyophilized to obtain 2'deoxy-5-fluoro-5'-TBDMS-uridine- 3'-adipic acid.2'deoxy-5-fluoro-5'-TBDMS-uridine-3'-adipate 0.5g dissolved in 20mL dimethyl sulfoxide, added CDI 0.2g, activated for 1 hour, added GPC 0.1g and DBU 0.2g The reaction was carried out at room temperature for 24 hours, and the precipitate was precipitated in cold diethyl ether, and separated by column chromatography to obtain bis(2'deoxy-5-fluoro-5'-TBDMS-uridine-3'-adipate) phosphatidylcholine, double (2 'Deoxy-5-fluoro-5'-TBDMS-uridine-3'-adipate) phosphatidylcholine was dissolved in tetrahydrofuran, tetrabutylammonium fluoride was added, and reacted at room temperature for 1 hour to remove the TBDMS protecting group. .Column chromatography gave the product bis(2'-deoxy-5-fluorouridine-3'-adipate) phosphatidylcholine.

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1840 - 1846
[2]Chemical and Pharmaceutical Bulletin,1996,vol. 44,p. 1196 - 1201
[3]Nucleosides, nucleotides and nucleic acids,2016,vol. 35,p. 178 - 194
[4]Patent: CN105288648,2018,B .Location in patent: Paragraph 0197
[5]Patent: WO2019/53476,2019,A1 .Location in patent: Page/Page column 38-39

13
[ 2493-04-1 ]
N-methyl-N-(4-chloro-n-butyl)amine hydrochloride [ No CAS ]
[ 50-91-9 ]
5-fluoro-2'-deoxyuridyl 5-nitrofurfuryl N-methyl-N-(4-chlorobutyl) phosphoramidate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4475 - 4480

14
[ 65-85-0 ]
[ 50-91-9 ]
[ 507232-12-4 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 995 - 1004

15
[ 18162-48-6 ]
[ 50-91-9 ]
[ 150109-68-5 ]

Yield	Reaction Conditions	Operation in experiment
97%		A solution of TBDMSCl (45.91 g, 304.6 mmol) and imidazole(24.27 g, 356.6 mmol) inCH2Cl2(200 mL) under argon was cooled to 0C for 10 minutes. 2'-Deoxy-5-fluorouridine (24.88 g, 101.1 mmol) dissolved in CH2Cl2 (100 mL) was added slowly, the reaction allowed to warm to room temperature and monitored by TLC (30% EtOAc:70% pet. spirit). After 20 hours, thereaction mixture was placedin a freezer (-20C) for 30 minutes (to precipitate the imidazole·HCl). The imidazole·HCl was filtered off and the filtrate washed with cold CH2Cl2 (2 × 25 mL). The filtrate was transferred to a separating funnel and washed withsaturated NaHCO3(aq)(3 × 100 mL) andbrine (1 × 100 mL), dried over anhydrous MgSO4 and concentrated in vacuo. The cruderesidue was purified byrecrystallisation from hot pet. spirit to yield 10 as a white solid (46.8 g, 97% yield). Rf = 0.78 (30% EtOAc:70% pet. spirit). M.P. 82-86C;O.R.[alpha]D25= +18.8 (c 1.00, CHCl3). IR (solid, nu/cm-1): 3469, 3360, 2952, 1737, 1655, 1628, 1592, 1504, 1472, 1458, 1436, 1372, 1317, 1255, 1144, 1091, 1066, 1025, 974, 884, 830, 783, 740, 676.1H NMR (500 MHz, CDCl3)delta 9.44 (br. s, 1H), 8.05 (d, J = 6.2 Hz, 1H), 6.29 (dt, J = 6.3, 1.5 Hz, 1H), 4.40 (dt, J = 6.0, 4.9 Hz, 1H), 3.95-3.90 (m, 2H), 3.76 (dd, J = 11.9, 2.2 Hz, 1H), 2.31 (ddd, J = 13.3, 6.1, 3.9 Hz, 1H), 2.05 (dt, J = 13.1, 6.4 Hz, 1H), 0.92 (s, 9H), 0.88 (s, 9H), 0.12 (d, J = 3.6 Hz, 6H), 0.07 (d, J = 3.0 Hz, 6H).13C NMR(126 MHz, CDCl3)delta 157.1 (d, J = 26.8 Hz), 149.0, 140.7 (d, J = 236.2 Hz), 124.4 (d, J = 34.1 Hz), 88.2, 85.7, 71.7, 62.8, 41.0, 26.0, 25.8, 18.5, 18.1, -4.5, -4.7, -5.4, -5.5.HREI-MS:m/z calculated for C21H40FN2O5Si2 [M+H+] 475.2454; observed 475.2460.
91%		To a solution of floxuridine 8 (300 mg, 1.22 mmol) in dry DMF (8 ml) was added imidazole (605 mg, 8.89 mmol) and stirred at room temperature for 5 mm. TBS-Cl (643 mg, 4.27 mmol) was then added to the mixture and the reaction stirred at room temperature for 2 h. The mixture was then concentrated in vacuo, dissolved in EtOAc (20 ml) and washed with H20 (20 ml). The aqueous layer was then washed Iwo more times with EtOAc. The organic layer were collected, washed with brine (60 ml), and dried over anhydrous MgSO4. The product was then purified by column chromatography with EtOAc/hexane (2:1, v/v, DCM (Rf 0.74, EtOAc 2: 1 Hexane) to yield TBS-protected compound 9 as a white solid 552 mg (91%). 1H NMR (500 MHz, CDCI3) 6 9.31 (d, J = 3.9, 1 H, NH), 8.04 (d, J = 6.3, 1H, ArH), 6.29 (td, J = 6,3, 1.6, IH, ArH), 4.44 -4.38 (m, 1H, ArH), 3.96 3.90 (m, 2H, CHr OH), 3.77 (t J = 6.0, IH), 2.32 (ddd, J = 13.3, 6.1,3.8, 1H), 2.09-2.01 (m, IH), 0.94-0.91 (m, 9H), 0.90-0.87 (m, 9H), 0.12(t J= 3.2, 6H), 0.07 (t, J = 2.8, 6H). 13C NMR (126 MHz, CDCI3) 6 157.05 (d, Jcc& = 26.9, C),148.98 (C), 140.63 (d, Jcp 236.6, C), 124.43 (d, JCCF- 34.0, CH), 88.23 (CH), 85.67 (CH), 71.67 (CH), 62.82 (CH2), 41.95 (CH2), 26.02 (CH3), 25.85 (CH3), 18.55 (C), 18.12 (C), -4.61 (dsjcH3, J = 31.1, CH3), -5.45 (d, JsIcI-13 3.2, CH3). LC-MS (m/z): 475.4

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 1215 - 1219
[2]Patent: WO2014/202994,2014,A1 .Location in patent: Page/Page column 96
[3]Journal of Medicinal Chemistry,2004,vol. 47,p. 1840 - 1846

16
[ 50-91-9 ]
[ 10356-76-0 ]

Reference： [1]Journal of Organic Chemistry,1992,vol. 57,p. 2989 - 2991
[2]Journal of Organic Chemistry,1992,vol. 57,p. 2989 - 2991

17
[ 33657-49-7 ]
[ 50-91-9 ]
[ 161632-24-2 ]

Yield	Reaction Conditions	Operation in experiment
58.9%	With sodium iodide; potassium carbonate	R.5.a REFERENCE EXAMPLE 5 (a) In the same manner as described in Reference Example 1(a) except for using 2.2 g of 5-fluoro-2'-deoxyuridine, 6.67 g of anhydrous potassium carbonate, 4.82 g of sodium iodide and 2.44 g of chloromethyl n-butanoate, there was prepared 1.82 g of 3-n-butanoyloxymethyl-2'-deoxy-5-fluorouridine in the form of white powder (yield: 58.9%). The melting point of the obtained powder was 103.0° to 105.0° C.
58.9%	With sodium iodide; potassium carbonate	25.a Preparation of the compound (I) wherein R1=CH3(CH2)2COO, R2=R3=CH3(CH2)6COO, R4=H, R=H, Y=F (a) The procedures of Example 1(a) were repeated except that 5-fluoro-2'-deoxyuridine (2.2 g, 8.94 mmol), anhydrous potassium carbonate (6.67 g), sodium iodide (4.82 g) and chloromethyl n-butyrate (2.44 g, 2 equivalents) were used to give 3-n-butyryloxymethyl-2'-deoxy-5-fluorouridine as white powder (1.82 g) (yield: 58.9 %) (melting point: 103.0 to 105.0°C).

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US5650172, 1997, A
[2]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - EP588317, 1994, A1

18
[ 76068-79-6 ]
[ 50-91-9 ]
[ 173531-00-5 ]

Yield	Reaction Conditions	Operation in experiment
61.1%	With sodium iodide; sodium chloride; potassium carbonate; In water; ethyl acetate; acetone;	(a) To 70 ml of acetone was added 4.95 g of 5-fluoro-2'-deoxyuridine and 12 g of sodium iodide. With stirring at room temperature, thereto was added 7.19 g of chloromethyl n-heptanoate and 15 g of anhydrous potassium carbonate. After the mixture was reacted with stirring at room temperature overnight, the obtained mixture was concentrated under reduced pressure. To the concentrate was added 150 ml of ethyl acetate, and then the insoluble matter was separated by filtration. The flitrate was washed with water, saturated aqueous solution of sodium chloride and water successively, followed by concentrating. The obtained concentrate was purified by silica gel column chromatography (eluding solvent: ethyl acetate) to give 4.77 g of 3-n-heptanoyloxymethyl-2'-deoxy-5-fluorouridine in the form of colorless solid matter (yield: 61.1%). The melting point of the obtained solid matter was 104 to 106 C.
61.1%	With sodium iodide; potassium carbonate;	(a) The procedures of Example 1(a) were repeated except that 5-fluoro-2'-deoxyuridine (4.95 g, 20.1 mmol), anhydrous potassium carbonate (15 g), sodium iodide (12 g, 80 mmol) and chloromethyl n-heptanoate (7.19 g, 40.2 mmol) were used to give 3-n-heptanoyloxymethyl-2'-deoxy-5-fluorouridine as colorless solid (4.77 g) (yield: 61.1 %) (melting point: 104 to 106C).

Reference： [1]Patent: US5650172,1997,A
[2]Patent: EP588317,1994,A1

19
[ 1608-67-9 ]
[ 10416-59-8 ]
[ 50-91-9 ]
[ 103782-09-8 ]

Yield	Reaction Conditions	Operation in experiment
81.7%	With acetic acid; triethylamine;tin(IV) chloride; In methanol; dichloromethane;	REFERENCE EXAMPLE 2 Preparation of 2'-deoxy-5-fluoro-3-(2-tetrahydrofuranyl)uridine A 16.5 g quantity of N,O-bis(trimethylsilyl) acetamide was added to a suspension of 5.00 g of 2'-deoxy-5-fluorouridine in 50 ml of dry dichloromethane at room temperature with stirring, and the mixture was stirred for four hours. Then a solution of 4.00 g of 2-acetoxytetrahydrofuran and 1.17 ml of stannic chloride in 10 ml of dry dichloromethane was added and the mixture was stirred for 1.5 hours. Then 8.0 ml of triethylamine was added to neutralize the mixture and the mixture was washed with water. The dichloromethane layer was concentrated and the residue was dissolved in 100 ml of methanol. A 3 ml quantity of acetic acid was added thereto and the mixture was left to stand at 40 C. for 3 hours. The solvent was distilled off and the residue was applied to a silica gel column to conduct gradient elution using chloroform and methanol (up to 4%)-chloroform mixtures, giving 5.25 g of 2'-deoxy-5-fluoro-3-(2-tetrahydrofuranyl)uridine as an oil in a yield of 81.7%. 1 H-NMR (CDCl3)delta: 8.06 (1H, d, J=6 Hz, C6 --H) 6.53 (1H, bt, J=6 Hz, STR40 6.23 (1H, bt, J=6 Hz, C1' --H) 4.45-3.75 (8H, m, C3'.4'.5' --H, C3'.5' --OH, STR41 2.29-2.16 (6H, m, C2' --H, STR42

Reference： [1]Patent: US4864021,1989,A

20
chloromethyl ester [ No CAS ]
[ 50-91-9 ]
3-n-butoxybutyryloxymethyl-2'-deoxy-5-fluorouridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.2%	With sodium iodide; potassium carbonate;	(a) The procedures of Example 1(a) were repeated except that 5-fluoro-2'-deoxyuridine (3.2 g, 13 mmol), anhydrous potassium carbonate (9.70 g, 70 mmol), sodium iodide (7.11 g, 47 mmol) and glutaric acid n-butyl and chloromethyl ester (6.2 g, 26 mmol) were used to give 3-n-butoxybutyryloxymethyl-2'-deoxy-5-fluorouridine (5.35 g) (yield: 92.2 %). IR(Neat): numax(cmmin1) 3500, 2970, 2930, 2880, 1735 FAB-MS (m/z): 447 (MH+)

Reference： [1]Patent: EP588317,1994,A1

21
[ 14243-64-2 ]
[ 50-91-9 ]
(5-fluoro-2'-deoxyuridinato-N₃)(triphenylphosphine)gold(I) [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1989,vol. 62,p. 1078 - 1080

22
[ 1135685-99-2 ]
[ 1192-07-0 ]
[ 50-91-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 941 - 944

23
[ 1135686-00-8 ]
[ 81778-07-6 ]
[ 50-91-9 ]

Yield	Reaction Conditions	Operation in experiment
	at 37℃; aq. phosphate buffer;

Reference： [1]Location in patent: scheme or table Ge, Yiyu; Wu, Xinghua; Zhang, Dazhi; Hu, Longqin [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 3, p. 941 - 944]

24
[ 75-77-4 ]
[ 50-91-9 ]
[ 54202-96-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at -10 - 0℃;Large scale;	A crude product of 5-fluoro-deoxyuridine was prepared by adding 10 Kg (40.61 mol) of the above biological method to 100 L of anhydrous methylene chloride,Then 16.96 Kg (121.85 mol) of triethylamine was added, the mixture was stirred,(89.34 mol) of TMS-Cl was added dropwise under stirring, and the reaction was carried out at 0-10 C. After solid solution, the reaction was complete and the reaction was complete.After the reaction is complete, 50L of deionized water is added dropwise to the system, and the internal temperature does not exceed 10 C. After dripping, the lower layer is separated and the lower layer is extracted again with 50 L of water. The water phase is discarded and the lower layer is at 40-45 C And the purified 3 ', 5'-di-TMS-5-fluoro-deoxyuridine nucleoside intermediates were purified under reduced pressure, and the HPLC purity was 99.94%

Reference： [1]Molecules,2011,vol. 16,p. 5655 - 5664
[2]Patent: CN103897007,2017,B .Location in patent: Paragraph 0041; 0042; 0043; 0044; 0045; 0046; 0047

25
[ 906670-24-4 ]
[ 50-91-9 ]
[ 1332837-31-6 ]

Yield	Reaction Conditions	Operation in experiment
8%	With 1-methyl-1H-imidazole; In tetrahydrofuran; at 20℃;Inert atmosphere;	A solution of the appropriate nucleoside (1.0 equiv.) in dry THF (10 mL) was added to NMI (5.0 equiv.) at room temperature under argon atmosphere. After 10 min the reaction mixture was added dropwise to a solution of phosphorochloridate (3.0 equiv) in anhydrous THF. The reaction was stirred at room temperature overnight and evaporated in vacuo. The oil obtained was dissolved in CH2CI2, washed twice with H2O, then with HC1 0.5 M or in alternative the crude product was washed with diethyl ether. Then the crude product was purified by column chromatography on silica, eluting with Ch Ch-MeOH as a gradient to afford the phosphoramidate. The phosphoramidate was prepared using 5-Fluoro- 2'deoxyuridine (0.25 g, 1.01 mmol), NMI (0.40 mL, 5.07 mmol) and naphthyl(benzyl-L-alaninyl) phosphorochloridate (0.82 g, 3.04 mmol) according to the general procedure C. Purification by gradient column chromatography eluting with CH2CI2 until CH2Cl2-MeOH (95:5) afforded the title compound as a colourless solid (47.0 mg, 8%) [Rf = 0.19 (CH2Cl2-MeOH, 95:5)], (Found: MNa+, 636.1520. C29H29N309FNaP requires [MNa+], 636.1523); 31P NMR (202 MHz, MeOD, mixture of diastereoisomers): deltaRho 4.24, 4.59; 19F NMR (470 MHz, MeOD): 5F -167.36, -167.18; W NMR (500 MHz, MeOD): deltaEta 1.34-1.38 (m, 3H, CHCH3), 1.67-1.79 (m, 1H, H-2'), 2.08- 2.17 (m, 1H, H-2'), 4.03-4.15 (m, 2H, CHCH3, H-4'), 4.24-4.36 (m, 3H, CH2OP, H-3'), 5.08 (d, 1H = 12.0 Hz, OCHHPh), 5.13 (d, 1HJ = 12.0 Hz, OCHHPh), 6.09-6.16 (m, 1H, H-l'), 7.27-7.45 (m, 6H, ArH), 7.47-7.55 (m, 3H, ArH], 7.67-7.72 (m, 2H, ArH, H- 6), 7.86-7.90 (m, 1H, ArH], 8.12-8.18 (m, 1H, ArH); 13C NMR (125 MHz, MeOD): 6C 20.3 (d, 3/c-p = 7.6 Hz, CH3), 20.5 (d, = 6.5 Hz, CH3), 40.8 (CH2), 40.9 (CH2), 51.8 (CH), 51.9 (CH), 67.6 (d, 2Jc-p = 5.3 Hz, CH2), 67.8 (d, 2JC-P = 5.2 Hz, CH2), 68.0 (CH2), 68.1 (CH2), 72.0 (CH), 72.1 (CH), 86.7 (d, 3JC-P = 8.1 Hz, CH), 86.8 (d, yC-p = 8.1 Hz, CH), 86.9 (CH), 87.0 (CH), 116.2 (d, 3JC-P = 3.3 Hz, CH), 116.5 (d, yC-p = 3.5 Hz, CH), 122.6 (CH), 125.3 (CH), 125.4 (CH), 125.6 (CH), 125.7 (CH), 126.2 (CH), 126.5 (CH), 126.6 (CH), 127.6 (CH), 127.7 (CH), 127.8 (C), 127.9 (C), 128.0 (CH), 128.1 (CH), 128.9 (CH), 129.0 (CH), 129.4 (CH), 129.5 (CH), 129.6 (CH), 129.7 (CH), 136.2 (C), 137.1 (C), 137.2 (C), 141.6 (d, 1JC-F = 233.8 Hz, C), 141.7 (d, I/C-F = 233.9 Hz, C), 147.8 (d, 2Jc-p = 7.7 Hz, C), 147.9 (d, 2Jc-p = 7.4 Hz, C), 150.5 (d, *JC-F = 4.0 Hz, C), 159.3 (d,JC-F = 26.1 Hz, C), 174.6 (d, 3/c-p = 5.0 Hz, C), 174.9 (d, yC-p = 4.3 Hz, C), m/z (ES) 636 (MH+, 100%), Reverse HPLC eluting with (H20/MeOH from 100/0 to 0/100) in 45 min., showed two peaks of the diastereoisomers with £R 34.23 min. and £R 34.59 min. Anal. Calcd for C29H29FN3O9P: C, 56.77; H, 4.76; N, 6.85. Found: C, 56.57; H, 5.06; N, 6.72. Radioactive pyrimidine deoxynucleosides
8%	With 1-methyl-1H-imidazole; In tetrahydrofuran; at 20℃;Inert atmosphere;	Synthesis of 5-Fluoro-2?deoxyuridine-5?-O-[alpha-naphthyl(benzyl-L-alaninyl)]phosphate (1) [0094] The phosphoramidate was prepared using 5-Fluoro-2?deoxyuridine (0.25 g, 1.01 mmol), NMI (0.40 mL, 5.07 mmol) and naphthyl(benzyl-L-alaninyl) phosphorochloridate (0.82 g, 3.04 mmol) according to the general procedure C. Purification by gradient column chromatography eluting with CH2Cl2 until CH2Cl2-MeOH (95:5) afforded the title compound as a colourless solid (47.0 mg, 8%) [Rf=0.19 (CH2Cl2-MeOH, 95:5)], (Found: MNa+, 636.1520. C29H29N3O9FNaP requires [MNa+], 636.1523); 31P NMR (202 MHz, MeOD, mixture of diastereoisomers): deltaP 4.24, 4.59; 19F NMR (470 MHz, MeOD): deltaF-167.36, -167.18; 1H NMR (500 MHz, MeOD): deltaH1.34-1.38 (m, 3H, CHCH3), 1.67-1.79 (m, 1H, H-2?), 2.08-2.17 (m, 1H, H-2?), 4.03-4.15 (m, 2H, CHCH3, H-4?), 4.24-4.36 (m, 3H, CH2OP, H-3?), 5.08 (d, 1H, J=12.0 Hz, OCHHPh), 5.13 (d, 1H, J=12.0 Hz, OCHHPh), 6.09-6.16 (m, 1H, H-1?), 7.27-7.45 (m, 6H, ArH), 7.47-7.55 (m, 3H, ArH), 7.67-7.72 (m, 2H, ArH, H-6), 7.86-7.90 (m, 1H, ArH), 8.12-8.18 (m, 1H, ArH); 13C NMR (125 MHz, MeOD): deltaC 20.3 (d, 3JC-P=7.6 Hz, CH3), 20.5 (d, 3JC-P=6.5 Hz, CH3), 40.8 (CH2), 40.9 (CH2), 51.8 (CH), 51.9 (CH), 67.6 (d, 2JC-P=5.3 Hz, CH2), 67.8 (d, 2JC-P=5.2 Hz, CH2), 68.0 (CH2), 68.1 (CH2), 72.0 (CH), 72.1 (CH), 86.7 (d, 3JC-P=8.1 Hz, CH), 86.8 (d, 3JC-P=8.1 Hz, CH), 86.9 (CH), 87.0 (CH), 116.2 (d, 3JC-P=3.3 Hz, CH), 116.5 (d, 3JC-P=3.5 Hz, CH), 122.6 (CH), 125.3 (CH), 125.4 (CH), 125.6 (CH), 125.7 (CH), 126.2 (CH), 126.5 (CH), 126.6 (CH), 127.6 (CH), 127.7 (CH), 127.8 (C), 127.9 (C), 128.0 (CH), 128.1 (CH), 128.9 (CH), 129.0 (CH), 129.4 (CH), 129.5 (CH), 129.6 (CH), 129.7 (CH), 136.2 (C), 137.1 (C), 137.2 (C), 141.6 (d, 1JC-F=233.8 Hz, C), 141.7 (d, 1JC-F=233.9 Hz, C), 147.8 (d, 2JC-P=7.7 Hz, C), 147.9 (d, 2JC-P=7.4 Hz, C), 150.5 (d, 4JC-F=4.0 Hz, C), 159.3 (d, 2JC-F=26.1 Hz, C), 174.6 (d, 3JC-P=5.0 Hz, C), 174.9 (d, 3JC-P=4.3 Hz, C), m/z (ES) 636 (MH+, 100%), Reverse HPLC eluting with (H2O/MeOH from 100/0 to 0/100) in 45 min., showed two peaks of the diastereoisomers with tR 34.23 min. and tR 34.59 min. Anal. Calcd for C29H29FN3O9P: C, 56.77; H, 4.76; N, 6.85. Found: C, 56.57; H, 5.06; N, 6.72.
0.11g		0.25 g of 5-fluoro-2'-deoxyuridine (5-FdU) was dissolved in 10 mL of dry tetrahydrofuran, and 1 ml of 1 M tert-butylmagnesium chloride in THF was added and stirred for 0.5 h.A solution of 0.8 g of ii-2 dissolved in 2 ml of THF was added with stirring and stirred for 12 h. The organic layer was evaporated to dryness, and the residue was applied to silica gel column chromatography, eluting with methylene chloride:methanol:triethylamine (100:5:1). 0.11g

Reference： [1]Biochemical Pharmacology,2011,vol. 82,p. 441 - 452
[2]Patent: WO2012/117246,2012,A1 .Location in patent: Page/Page column 25-26; 34-35
[3]Patent: US2014/57866,2014,A1 .Location in patent: Paragraph 0094
[4]Journal of Medicinal Chemistry,2011,vol. 54,p. 7247 - 7258
[5]Patent: CN109134568,2019,A .Location in patent: Paragraph 0042-0043; 0046; 0047

26
[ 142629-80-9 ]
[ 50-91-9 ]
[ 232925-20-1 ]

Yield	Reaction Conditions	Operation in experiment
4%	With 1-methyl-1H-imidazole; In tetrahydrofuran; at -78 - 20℃;Inert atmosphere;	To a stirring solution of 5-F-dUrd (1.0 eq.) in anhydrous THF, an appropriate phosphorochloridate (3.0 eq.) dissolved in anhydrous THF was added dropwise under an Ar atmosphere. To that reaction mixture at -78C was added dropwise over 5 minutes NMI (5.0 eq.). After 15 minutes, the reaction mixture was let to rise to room temperature and stirred overnight. The solvent was removed under vacuum and the residue was re-dissolved in DCM and washed with 0.5 M HC1 three times. The organic layer was dried over MgSCH, filtered, reduced to dryness and purified by column chromatography with gradient of eluent (DCM/MeOH 99:1 to 97:3 to 95:5). The phosphoramidate was prepared using 5-fluoro-2'-deoxyuridine (0.25 g, 1.01 mmol), iV-methylimidazole (NMI) (0.40 mL, 5.07 mmol) and phenyl (methoxy-L- alaninyl) phosphorochloridate (0.84 g, 3.04 mmol) according to general procedure D. Purification by gradient column chromatography eluting with CH2CI2 until CH2Cl2-MeOH (95:5) afforded the title compound as a colourless solid (16.0 mg, 4%) [Rf = 0.30 (CH2Cl2-MeOH, 95:5)], (Found: MNa+, 510.1045. CigfeNsOgNaPF requires [MNa+], 510.1054); 31P NMR (202 MHz, MeOD):P 3.79, 4.09; 19F NMR (470 MHz, MeOD) :F -167.78, -167.72; *H NMR (500 MHz, MeOD):H 1.34 (d, 3HJ = 7.1 Hz, CHCH3, one diast), 1.36 (d, 3HJ = 7.1 Hz, CHCH3, one diast), 2.02-2.16 (m, 1H, -2' 2.25-2.34 (m, 1H, H-2'), 3.69 (s, 3H, OCH3, one diast), 3.70 (s, 3H, OCH3, one diast), 3.93-4.02 (m, 1H, CHCH3), 4.08-4.13 (m, 1H, H-4'), 4.27-4.45 (m, 3H, CH2OP, H-3' 6.20-6.29 (m, 1H, H-V), 7.18-7.28 (m, 3H, Ar/f), 7.35-7.40 (m, 2H, ArH), 7.85 (d, 1H, = 6.4 Hz, H-6); 13C NMR (125 MHz, MeOD):c 20.2 (d, /C-p = 7.5 Hz, CH3), 20.5 (d, yC-p = 6.7 Hz, CH3), 40.8 (CH2), 40.9 (CH2), 51.5 (CH3), 51.6 (CH3), 52.7 (CH), 52.8 (CH), 67.5 (d, 2Jc-p = 5.5 Hz, CH2), 67.6 (d, 2JC-P = 5.1 Hz, CH2), 72.0 (CH), 72.1 (CH), 86.7 (d, 3/C-P = 8.2 Hz, CH), 86.8 (d, 3/c-p = 8.2 Hz, CH), 86.9 (CH), 87.0 (CH), 121.2 (d, yC-p = 4.5 Hz, CH), 121.4 (d, 3JC-P = 4.7 Hz, CH), 125.6 (d, 5/c-P = 2.9 Hz, CH), 125.9 (d, 5Jc-p = 2.9 Hz, CH), 126.2 (CH), 130.8 (CH), 130.9 (CH), 141.6 (d, C-F = 233.8 Hz, C), 141.7 (d, yC-F = 233.9 Hz, C), 150.6 (d, 4/c-f = 3.6 Hz, C), 152.1 (d, 2JC-P = 6.8 Hz, C), 152.2 (d, 2Jc-p = 6.8 Hz, C), 159.4 (d, 2JC-F = 26.0 Hz, C), 175.2 (d, 37C-P = 4.8 Hz, C), 175.5 (d, 3/c-p = 3.7 Hz, C), m/z (ES) 510 (MNa+, 100%); Reverse-phase HPLC eluting with H20/MeOH from 100/0 to 0/100 in 45 minutes, 1 ml/min, L = 275 nm, showed two peaks of the diastereoisomers with tR 23.11 min. and tR 24.11 min. (74% : 24%).
4%	With 1-methyl-1H-imidazole; In tetrahydrofuran; at -78 - 20℃;Inert atmosphere;	5-Fluoro-2?-deoxyuridine-5?-O-[phenyl(methoxy-L-alaninyl)]phosphate (CPF382) Reference Example [0100] [0101] The phosphoramidate was prepared using 5-fluoro-2?-deoxyuridine (0.25 g, 1.01 mmol), N-methylimidazole (NMI) (0.40 mL, 5.07 mmol) and phenyl(methoxy-L-alaninyl)phosphorochloridate (0.84 g, 3.04 mmol) according to general procedure D. Purification by gradient column chromatography eluting with CH2Cl2 until CH2Cl2-MeOH (95:5) afforded the title compound as a colourless solid (16.0 mg, 4%) [Rf=0.30 (CH2Cl2-MeOH, 95:5)], (Found: MNa+, 510.1045. C19H23N3O9NaPF requires [MNa+], 510.1054); 31P NMR (202 MHz, MeOD): TMP 3.79, 4.09; 19F NMR (470 MHz, MeOD): TMF -167.78, -167.72; 1H NMR (500 MHz, MeOD): TMH 1.34 (d, 3H, J=7.1 Hz, CHCH3, one diast.), 1.36 (d, 3H, J=7.1 Hz, CHCH3, one diast.), 2.02-2.16 (m, 1H, H-2?), 2.25-2.34 (m, 1H, H-2?), 3.69 (s, 3H, OCH3, one diast.), 3.70 (s, 3H, OCH3, one diast.), 3.93-4.02 (m, 1H, CHCH3), 4.08-4.13 (m, 1H, H-4?), 4.27-4.45 (m, 3H, CH2OP, H-3?), 6.20-6.29 (m, 1H, H-1?), 7.18-7.28 (m, 3H, ArH), 7.35-7.40 (m, 2H, ArH), 7.85 (d, 1H, 3JH-F=6.4 Hz, H-6); 13C NMR (125 MHz, MeOD): TMC 20.2 (d, 3JC-P=7.5 Hz, CH3), 20.5 (d, 3JC-P=6.7 Hz, CH3), 40.8 (CH2), 40.9 (CH2), 51.5 (CH3), 51.6 (CH3), 52.7 (CH), 52.8 (CH), 67.5 (d, 2JC-P=5.5 Hz, CH2), 67.6 (d, 2JC-P=5.1 Hz, CH2), 72.0 (CH), 72.1 (CH), 86.7 (d, 3JC-P=8.2 Hz, CH), 86.8 (d, 3JC-P=8.2 Hz, CH), 86.9 (CH), 87.0 (CH), 121.2 (d, 3JC-P=4.5 Hz, CH), 121.4 (d, 3JC-P=4.7 Hz, CH), 125.6 (d, 5JC-P=2.9 Hz, CH), 125.9 (d, 5JC-P=2.9 Hz, CH), 126.2 (CH), 130.8 (CH), 130.9 (CH), 141.6 (d, 1JC-F=233.8 Hz, C), 141.7 (d, 1JC-F=233.9 Hz, C), 150.6 (d, 4JC-F=3.6 Hz, C), 152.1 (d, 2JC-P=6.8 Hz, C), 152.2 (d, 2JC-P=6.8 Hz, C), 159.4 (d, 2JC-F=26.0 Hz, C), 175.2 (d, 3JC-P=4.8 Hz, C), 175.5 (d, 3JC-P=3.7 Hz, C), m/z (ES) 510 (MNa+, 100%); Reverse-phase HPLC eluting with H2O/MeOH from 100/0 to 0/100 in 45 minutes, 1 ml/min, =275 nm, showed two peaks of the diastereoisomers with tR 23.11 min. and tR 24.11 min. (74%:24%).
1.1 g	With 1-methyl-1H-imidazole; In tetrahydrofuran; at -78℃; for 12h;	To a flame dried round bottom flask under inert atmosphere was added phenol (500 mg, 5.31 mmol), POCl3 (495 L, 5.31 mmol) and Et2O (200 mL). The reaction mixture was cooled to -78oC and slowly Et3N (740 L, 5.31 mmol) was added and the reaction mixture was stirred overnight. Next day, triethylamine hydrochloride was removed by filtration and the filtrate was evaporated in vacuo. To the residue was added DCM (200 mL) and L-alanine methylester hydrochloride (661 mg, 4.7 mmol). The reaction mixture was cooled to -78 oC and Et3N (1.32 mL, 9.4 mmol) was added slowly. The reaction mixture was stirred overnight and the solvent was evaporated in vacuo next day. The residue was dissolved in Et2O (200 mL) and triethylamine hydrochloride was removed by filtration. The filtrate was evaporated in vacuo to yield semisolid product, which was used without purification (31P NMR (162 MHz, CDCl3) delta 8.27, 7.94). To a stirred suspension of 5-fluoro-2'-deoxyuridine (371 mg, 1.5 mmol) in THF (20 mL) at -78oC was added the above product (1.39 g, 5.00 mmol). N-methylimidazole (401 , 5.00 mmol) was added and the reaction mixture was stirred for 12 h. The solvent was evaporated in vacuo and the residue was purified by silica gel column chromatography (4% MeOH in DCM) to yield 3 (1.10 g, 40%) as a white fluffy solid.

Reference： [1]Patent: WO2012/117246,2012,A1 .Location in patent: Page/Page column 27; 29
[2]Patent: US2014/57866,2014,A1 .Location in patent: Paragraph 0100-0101
[3]Journal of Medicinal Chemistry,2011,vol. 54,p. 7247 - 7258
[4]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4497 - 4501

27
[ 183370-70-9 ]
[ 50-91-9 ]
[ 1338052-09-7 ]

Yield	Reaction Conditions	Operation in experiment
8%		To a stirring solution of 5-FdUrd (1.0 eq.) dissolved in anhydrous THF, fBuMgCl (1.1 mol eq. 1M solution in THF) was added dropwise under an Ar atmosphere, followed by addition (after 30 min.) of the appropriate phosphorochloridate (2.0 mol eq.) dissolved in anhydrous THF. The resulting reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue was purified by column chromatography using gradient of eluent (DCM/MeOH 99:1 to 97:3 to 95:5) The phosphoramidate was prepared using 5-fluoro-2'-deoxyuridine (0.40 g, 1.62 mmol), tert-butylmagnesium chloride in tetrahydrofuran (tBuMgCl) (1.0 M, 2.43 mL, 2.43 mmol) and phenyl (benzoxy-L-alaninyl) phosphorochloridate (1.08 g, 3.20 mmol) according to general procedure E. Purification by gradient column chromatography on silica, eluting with CH2CI2 until CH Ch-MeOH (95:5) afforded the title compound as a colourless solid (71.0 mg, 8%) [Rf = 0.35 (CH2Cl2-MeOH, 95:5)], (Found: MNa+, 586.1360. C25H27N309NaPF requires [MNa+], 586.1367); 31P NMR (202 MHz, MeOD):P 3.74, 4.14; 19F NMR (470 MHz, MeOD):F -167.57, - 167.46; *H NMR (500 MHz, MeOD):H 1.35 (d, 3HJ = 7.4 Hz, CHCH3, one dias ), 1.37 (d, 3H = 6.9 Hz, CHCH3, one diast), 1.96-2.32 (m, 2H, H-2'), 3.95-4.08 (m, 2H, CHCH3, H-4'), 4.23-4.34 (m, 3H, CH2OP, H-3'), 5.13 (br d, 1HJ = 12.3 Hz, OCHHPh), 5.16 (br d, 1HJ = 12.3 Hz, OCHHPh, one diast.), 5.17 (br d, 1HJ = 12.2 Hz, OCHHPh, one diast), 6.16-6.22 (m, 1H, H-l'), 7.17-7.25 (m, 3H, ArH), 7.26-7.40 (m, 7H, ArH), 7.81-7.85 (m, 1H, H-6); 13C NMR (125 MHz, MeOD):c 20.2 (d, 3/C-P = 7.5 Hz, CH3), 20.4 (d, 3/c-p = 6.2 Hz, CH3), 40.6 (CH2), 40.9 (CH2), 51.6 (CH), 51.8 (CH), 67.5 (d, 2JC-P = 5.3 Hz, CH2), 67.6 (d, 2JC-P = 5.5 Hz, CH2), 68.0 (CH2), 71.8 (CH), 71.9 (CH), 86.6 (d, 3Jc-p = 8.0 Hz, CH), 86.8 (d, Jc-p = 8.3 Hz, CH), 86.9 (CH), 87.0 (CH), 121.4 (d, /c-p = 5.1 Hz, CH), 121.5 (d, yC-p = 5.6 Hz, CH), 125.5 (d, 5/C-P = 3.2 Hz, CH), 125.8 (d, = 3.2 Hz, CH), 126.3 (CH), 129.0 (CHx2), 129.3 (CHx2), 129.6 (CHx2), 130.8 (CHx2), 140.9 (C), 141.6 (d, = 233.6 Hz, C), 150.7 (d, 4/C-F = 5.7 Hz, C), 152.1 (d, 2JC-F = 6.5 Hz, C), 159.2 (d, 2JC-F = 26.3 Hz, C), 174.6 (d, /C-P = 4.9 Hz, C), 174.7 (d, yc-p = 4.9 Hz, C), m/z (ES) 586 (MNa+, 100%); Reverse-phase HPLC eluting with H20/MeOH from 100/0 to 0/100 in 45 minutes, 1 ml/min, L = 275 nm, showed one peak of the mixture of diastereoisomers with tR 25.08 min. (97%).
8%	With tert-butylmagnesium chloride; In tetrahydrofuran; at 20℃;Inert atmosphere;	5-Fluoro-2?-deoxyuridine-5?-O-[phenyl(benzoxy-L-alaninyl)]phosphate (CPF381) [0098] [0099] The phosphoramidate was prepared using 5-fluoro-2?-deoxyuridine (0.40 g, 1.62 mmol), tert-butylmagnesium chloride in tetrahydrofuran (tBuMgCl) (1.0 M, 2.43 mL, 2.43 mmol) and phenyl(benzoxy-L-alaninyl)phosphorochloridate (1.08 g, 3.20 mmol) according to general procedure E. Purification by gradient column chromatography on silica, eluting with CH2Cl2 until CH2Cl2-MeOH (95:5) afforded the title compound as a colourless solid (71.0 mg, 8%) [Rf=0.35 (CH2Cl2-MeOH, 95:5)], (Found: MNa+, 586.1360. C25H27N3O9NaPF requires [MNa+], 586.1367); 31P NMR (202 MHz, MeOD): TMP 3.74, 4.14; 19F NMR (470 MHz, MeOD): TMF-167.57, -167.46; 1H NMR (500 MHz, MeOD): TMH 1.35 (d, 3H, J=7.4 Hz, CHCH3, one diast.), 1.37 (d, 3H, J=6.9 Hz, CHCH3, one diast.), 1.96-2.32 (m, 2H, H-2?), 3.95-4.08 (m, 2H, CHCH3, H-4?), 4.23-4.34 (m, 3H, CH2OP, H-3?), 5.13 (br d, 1H, J=12.3 Hz, OCHHPh), 5.16 (br d, 1H, J=12.3 Hz, OCHHPh, one diast.), 5.17 (br d, 1H, J=12.2 Hz, OCHHPh, one diast.), 6.16-6.22 (m, 1H, H-1?), 7.17-7.25 (m, 3H, ArH), 7.26-7.40 (m, 7H, ArH), 7.81-7.85 (m, 1H, H-6); 13C NMR (125 MHz, MeOD): TMC 20.2 (d, 3HC-P=7.5 Hz, CH3), 20.4 (d, 3JC-P=6.2 Hz, CH3), 40.6 (CH2), 40.9 (CH2), 51.6 (CH), 51.8 (CH), 67.5 (d, 2JC-P=5.3 Hz, CH2), 67.6 (d, 2JC-P=5.5 Hz, CH2), 68.0 (CH2), 71.8 (CH), 71.9 (CH), 86.6 (d, 3JC-P=8.0 Hz, CH), 86.8 (d, 3JC-P=8.3 Hz, CH), 86.9 (CH), 87.0 (CH), 121.4 (d, 3JC-P=5.1 Hz, CH), 121.5 (d, 3JC-P=5.6 Hz, CH), 125.5 (d, 5JC-P=3.2 Hz, CH), 125.8 (d, 5JC-P=3.2 Hz, CH), 126.3 (CH), 129.0 (CH×2), 129.3 (CH×2), 129.6 (CH×2), 130.8 (CH×2), 140.9 (C), 141.6 (d, 1JC-F=233.6 Hz, C), 141.7 (d, 1JC-F=233.6 Hz, C), 150.7 (d, 4JC-F=5.7 Hz, C), 152.1 (d, 2JC-P=6.5 Hz, C), 159.2 (d, 2JC-F=26.3 Hz, C), 174.6 (d, 3JC-P=4.9 Hz, C), 174.7 (d, 3JC-P=4.9 Hz, C), m/z (ES) 586 (MNa+, 100%); Reverse-phase HPLC eluting with H2O/MeOH from 100/0 to 0/100 in 45 minutes, 1 ml/min, =275 nm, showed one peak of the mixture of diastereoisomers with tR 25.08 min. (97%).

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 7247 - 7258
[2]Patent: WO2012/117246,2012,A1 .Location in patent: Page/Page column 27-28
[3]Patent: US2014/57866,2014,A1 .Location in patent: Paragraph 0098-0099

28
[ 32991-17-6 ]
[ 50-91-9 ]
C₂₂H₃₃FN₄O₉ [ No CAS ]
C₂₂H₃₃FN₄O₉ [ No CAS ]
C₃₅H₅₅FN₆O₁₃ [ No CAS ]

Reference： [1]Pharmaceutical Research,2011,vol. 28,p. 2575 - 2588
[2]Molecules,2012,vol. 17,p. 3672 - 3689

29
[ 1384863-38-0 ]
[ 50-91-9 ]
[ 1384863-42-6 ]

Yield	Reaction Conditions	Operation in experiment
34%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; acetonitrile; at 20℃; for 2h;	To the reaction flask was added 5-fluoro-2'-deoxyuridine (300 mg, 1.21 mmol), DBU (437 L, 2.92 mmol), ACN (50 mL). The reaction mixture was stirred at room temperature and compound 1b (601 mg, 1.45 mmol) dissolved in DCM (50 mL) was added slowly. After 2 h the solvent was evaporated in vacuo and the residue was purified by silica gel column chromatography (6% MeOH in DCM) to yield 2b (160 mg, 34%) as a white solid.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4497 - 4501

30
[ 91-01-0 ]
[ 50-91-9 ]
[ 1454883-42-1 ]

Yield	Reaction Conditions	Operation in experiment
64%	With palladium dichloride; In 1,2-dichloro-ethane; at 85℃; for 16h;Inert atmosphere;	General procedure: To a solution of the respective nucleoside (100 mg) and diphenylmethanol in dichloroethane(5 mL/mmol) was added palladium chloride (0.2 eq). The reaction mixture was heated at 85 C underan argon atmosphere for 16 h or until disappearance of the starting materials as monitored by TLC.The solvent was removed in vacuo and the crude mixture obtained was purified by columnchromatography to afford the desired compound.

Reference： [1]Molecules,2013,vol. 18,p. 8524 - 8534

31
[ 91-01-0 ]
[ 50-91-9 ]
[ 1454883-43-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	With palladium dichloride; In 1,2-dichloro-ethane; at 85℃; for 16h;Inert atmosphere;	General procedure: To a solution of the respective nucleoside (100 mg) and diphenylmethanol in dichloroethane(5 mL/mmol) was added palladium chloride (0.2 eq). The reaction mixture was heated at 85 C underan argon atmosphere for 16 h or until disappearance of the starting materials as monitored by TLC.The solvent was removed in vacuo and the crude mixture obtained was purified by columnchromatography to afford the desired compound.
	With palladium dichloride; In 1,2-dichloro-ethane; at 85℃;Inert atmosphere;	General procedure: To a solution of the respective nucleoside (100mg) and diphenylmethanol in dichloroethane (5mL/mmol) was added palladium chloride (0.2eq). The reaction mixture was heated at 85C under Argon atmosphere for 16h or until disappearance of the starting materials. The reaction was monitored by TLC. The solvent was removedin vacuoand the crude mixture obtained was purified by column chromatography to afford the desired compound. Analytical details for the different compounds obtained can be found in Ref.[15].

Reference： [1]Molecules,2013,vol. 18,p. 8524 - 8534
[2]European Journal of Medicinal Chemistry,2014,vol. 76,p. 98 - 109

32
[ 51-21-8 ]
[ 50-89-5 ]
[ 50-91-9 ]

Yield	Reaction Conditions	Operation in experiment
35%	With Lactobacillus animalis ATCC 35046 2?-N-deoxyribosyltransferase immobilized in DEAE-Sepharose; In aq. buffer; at 30℃;pH 7.0;Green chemistry; Enzymatic reaction;	General procedure: Thymidine (dThd) and 2'-deoxyuridine (dUrd) were assayed as sugar donors. Different purine and pyrimidine bases were tested: 5-fluorouracil (5FUra), 5-bromouracil (5BrUra), 5-chlorouracil (5ClUra), 6-chloropurine (6ClPur), 6-bromopurine (6BrPur) and 6-chloro-2-fluoropurine (6Cl2FPur). Reactions were performed using 100 mg/mL of immobilized LaNDT, 6 mM nucleoside and 2 mM base, 30 C and 200 rpm. At different times (5-8 h), 20 muL aliquots were taken and centrifuged at 10,000 x g, and the supernatant was analyzed by HPLC to evaluate yield expressed as percentage and product conversion expressed as mg of product per gram of support.
	With ammonium dihydrogen phosphate; ammonia; In water; at 45 - 55℃; for 45h;pH 6.6;Large scale; Enzymatic reaction;	35Kg beta-thymidine, 21Kg 5-fluorouracil,8.4Kg ammonium dihydrogen phosphate used1750L pure water stirring suspended,With 2.8L concentrated ammonia to adjust the pH = 6.6,Adding 0.75Kg of industrial nucleoside phosphorylase,Stir,Temperature control 45-55 C reaction.After 45 hours of reaction,HPLC monitoring to complete reaction.After the reaction is complete,The reaction system was cooled to room temperature,Centrifugal,Remove insoluble matter,Centrifuge the mother liquor to adjust pH = 8-9,It was then purified with 900 L Cl-type strongly basic resin (eluted with deionized water)A fraction containing 5-fluoro-deoxyuridine and a beta-thymidine content of less than 3%The partially collected solution was then concentrated to dryness at 60 C under reduced pressure,Remove the solid,At 60-65 C under the blast drying to less than 1% moisture,This is the 5 - fluoro - deoxyuridine nucleoside crude,HPLC purity 90.5%

Reference： [1]Journal of Fluorine Chemistry,2016,vol. 186,p. 91 - 96
[2]Organic and Biomolecular Chemistry,2013,vol. 11,p. 6900 - 6905
[3]Patent: CN103897007,2017,B .Location in patent: Paragraph 0102; 0103; 0104; 0105; 0106; 0107
[4]Catalysis science and technology,2019,vol. 9,p. 5122 - 5129

33
[ 4704-31-8 ]
[ 50-91-9 ]
[ 118694-11-4 ]
[ 118694-12-5 ]

Yield	Reaction Conditions	Operation in experiment
	With Novozym 435 from Candida antarctica; In acetone; at 40℃; for 4.5h;Enzymatic reaction;	General procedure: The solvents were dried by gentle shaking with 4 A molecular sieves overnight. Anhydrous organic solvent (2 mL), nucleoside (0.04 mmol), vinyl ester (0.28 mmol),and Novozym 435 (60 mg) were incubated in a 10-mL Erlenmeyer shaking flask capped with a septum and heated to 40 C over a water bath. Periodically, aliquotswere withdrawn from the reaction mixture and analyzed by HPLC. No chemical acylation was detectable as confirmed by the control experiments.

Reference： [1]Process Biochemistry,2013,vol. 48,p. 1208 - 1211

34
[ 3050-69-9 ]
[ 50-91-9 ]
[ 123739-84-4 ]
[ 123739-81-1 ]

Yield	Reaction Conditions	Operation in experiment
	With Novozym 435 from Candida antarctica; In acetone; at 40℃; for 3.5h;Enzymatic reaction;	General procedure: The solvents were dried by gentle shaking with 4 A molecular sieves overnight. Anhydrous organic solvent (2 mL), nucleoside (0.04 mmol), vinyl ester (0.28 mmol),and Novozym 435 (60 mg) were incubated in a 10-mL Erlenmeyer shaking flask capped with a septum and heated to 40 C over a water bath. Periodically, aliquotswere withdrawn from the reaction mixture and analyzed by HPLC. No chemical acylation was detectable as confirmed by the control experiments.

Reference： [1]Process Biochemistry,2013,vol. 48,p. 1208 - 1211

35
[ 5809-91-6 ]
[ 50-91-9 ]
[ 1111240-44-8 ]
[ 1111240-45-9 ]

Yield	Reaction Conditions	Operation in experiment
	With Novozym 435 from Candida antarctica; In acetone; at 40℃; for 5.5h;Enzymatic reaction;	General procedure: The solvents were dried by gentle shaking with 4 A molecular sieves overnight. Anhydrous organic solvent (2 mL), nucleoside (0.04 mmol), vinyl ester (0.28 mmol),and Novozym 435 (60 mg) were incubated in a 10-mL Erlenmeyer shaking flask capped with a septum and heated to 40 C over a water bath. Periodically, aliquotswere withdrawn from the reaction mixture and analyzed by HPLC. No chemical acylation was detectable as confirmed by the control experiments.

Reference： [1]Process Biochemistry,2013,vol. 48,p. 1208 - 1211

36
C₁₂H₁₃FN₂O₅ [ No CAS ]
[ 50-91-9 ]

Yield	Reaction Conditions	Operation in experiment
	With Pd0-functionalized PEG-PS resins; In aq. phosphate buffer; at 37℃; for 24h;	Figure 17 illustrates the palladium-mediated reactions of the drug precursors with Pd(0) under biocompatible conditions to form either 5FU, 1, or floxuridine, 8. In the table it iscompHed the conversion percentages and resulting products after incubating each of the drug precursors (100 pM) with lmglmL of Pd-resins in PBS for 24 h at 37 C(Thermomixer, shaker speed: 1,400 rpm). Values were calculated by HPLC using an UV detector.

Reference： [1]Patent: WO2014/202994,2014,A1 .Location in patent: Page/Page column 89

37
[ 16506-27-7 ]
[ 50-91-9 ]
C₂₅H₃₀Cl₂FN₅O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%		10109] In a typical procedure, FdU (280 mg, 1.14 mmol), DMAP (5 mg, 0.038 mmol), DCC (95 mg, 0.46 mmol) and TEA (53 IL, 0.38 mmol) were dissolved in anhydrous DMF (6 mE) and the mixture was stirred at room temperature under N2. After 15 mm, the BdM (53 pL, 0.38 mmol) in DMF (4 mE) was added dropwise and the reaction mixture was stirred for 48 h at room temperature. Then the reaction mixture was filtered to remove white solids (dicyclohexylurea) and the filtrate was concentrated under vacuum. The crude product was purified by column chromatograph using DCMJCH3OH (12:1, v/v) as the eluent. The product was collected and the solvent was removed by rotary evaporation to obtain FdUBdM conjugate (155mg, 69%). ?H NMR (400 MHz, DMSOd 5) oe (ppm) 11.85-11.84 (d, J=4.8 Hz, 1H), 7.91-7.90 (d,J=7.2 Hz, 1H), 7.32-7.30 (d, J=8.8 Hz, 1H), 6.89-6.88 (d,J=2.4 Hz, 1H), 6.78-6.76 (dd, J=8.8 Hz, 1H), 6.13-6.10 (t,J=13.2 Hz, 1H), 5.44-5.43 (d, J=4.4 Hz, 1H), 4.21-4.20 (d,J=4.8 Hz, 2H), 3.69 (m, 8H), 3.64 (s, 3H), 3.15-3.14 (t, J=5.2Hz, 2H), 2.84-2.80 (t, J=14.8 Hz, 2H), 2.01 (m, 1H), 2.11 (m,1H), 2.22-2.19 (t, J=13.2 Hz, 2H). ?3C NMR (100 MHz,DMSO-d5) oe (ppm) 173.07, 162.98, 157.79, 154.80, 149.65,143.20, 129.66, 125.57, 125.23, 111.01, 110.67, 102.42,85.22, 84.47,70.66, 64.51, 54.08,42.08,36.46,33.33,30.12,26.10, 22.69. ESI-MS m/z (M+H) calcd: 586.1637, found:586.1649.

Reference： [1]Patent: US2015/31644,2015,A1 .Location in patent: Paragraph 0109; 0110

38
[ 65-85-0 ]
[ 50-91-9 ]
2,3'-anhydro-5'-O-benzoyl-5-fluoro-2'-deoxvuridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With di-isopropyl azodicarboxylate; triphenylphosphine; In N,N-dimethyl-formamide; for 0.75h;	To a stirred solution of 5-fluoro-2'-deoxyuridine (3.69 g, 15 mmol) and triphenylphosphine (5.90g, 22.5 mmol) in anhydrous DMF (30 mL) a solution of benzoic acid (2.75 g, 22.5 mmol) anddiisopropyl azodicarboxylate (DIAD) (4.43 mL, 22.5 mmol) in anhydrous DMF (7 mL) wasaddeed portionwise using a syringe. After 15 min, another portion of DIAD (4.43 mL, 22.5 mmol)and triphenylphosphine (5.90 g, 22.5 mmol) in DMF (7 mL) was added, and the mixture was340 stirred for another 30 min. Subsequently, the reaction mixture was poured into cooled diethyl ether(370 mL), and the resulting suspension was stirred using a magnetic stirrer for 2 hours. White precipitate of the product was filtered using vacuum and washed with a volume of diethyl ether;this yielded 4.18 g (84%) of2.3'-anhydro-5'-0-benzoyl-5-fluoro-2'-deoxyuridine which was usedwithout purification in the subsequent stage of synthesis.345 1H NMR (DMSO-d6) 8: 2.55-2.69 (m, lH, H-2', H-2"), 3.17 (m, lH, H-4'), 3.52 (m, 2H, H-5', H-5"), 4.22 (m, lH, H-3'), 5.08 (pseudo t, lH, J = 6.1 Hz, H-1'), 6.84 (d, lH, J = 3.5 Hz, H-6),7.52-8.03 (m, 5H, Ph).13C NMR (DMSO-d6) 8: 31.26, 59.38, 77.52, 85.42, 87.34, 125.59 (d, J c-F = 36.8 Hz), 128.70,129.13, 130.19, 133.46, 144.27 (d, J c-F = 248.7 Hz), 151.70, 162.93 (d, J c-F = 16.3 Hz),350 166.84.19F NMR (DMSO-d6) 8: -158.46 (d, IF, J = 5.0 Hz).MS-ESI m/z: 333 [M + Ht; 355 [M +Nat; 371 [M + Kt; 331 [M- HL 367, 369 [M + Cir.

Reference： [1]Patent: WO2015/50467,2015,A1 .Location in patent: Page/Page column 19; 20

39
[ 3543-75-7 ]
[ 50-91-9 ]
C₂₅H₃₀Cl₂FN₅O₆ [ No CAS ]

Reference： [1]Molecular Pharmaceutics,2015,vol. 12,p. 2328 - 2336

40
[ 50-91-9 ]
2'-deoxy-5-fluorouridine 3'-O-triphosphate [ No CAS ]
2'-deoxy-5-fluorouridine 5'-O-triphosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%		5-Fluoro-deoxyuridine (60 mg, 0.244 mmol) was dried underreduce pressure at 80 C for 2 h. After cooling down, the F5dUwas suspended in trimethyl phosphate (0.6 ml) in argon purgedvial and POCl3 (27 lL, 0.294 mmol) was added. The mixturewas then stirred overnight at 0 C, an ice-cooled solution of(NHBu3)2H2P2O7 (600 mg, 1.09 mmol) and Bu3N (0.22 ml,0.92 mmol) in dry DMF (2.2 ml) was added and the mixture wasstirred at 0 C for another 1 h. Then the reaction was quenchedby addition of 2 M aqueous TEAB (0.5 ml) and the solvents wereevaporated in vacuo and the residue was co-distilled with waterseveral times. The product was purified twice by using semipreparativereversed-phase HPLC (C18) with TEAB in H2O (0.1 M)to TEAB in H2O/MeOH (1:1, 0.1 M) linear gradient as eluent. Severalco-distillations with water and conversion into the sodium saltform (Dowex 50WX8 in Na+ cycle) followed by freeze-drying fromwater gave white powder of 20-deoxy-5-fluoro uridine 50-Otriphosphateand 20-deoxy-5-fluoro uridine 30-O-triphosphate(33 mg, 75:25, 22% yield of 50-O-triphosphate). F5dUTP: 1H NMR(400 MHz, D2O, ref(dioxane) = 3.75 ppm) d 8.07 (d, J = 6.4 Hz, 1H,H-6), 6.29 (t, J = 6.6 Hz, 1H, H-10), 4.70-4.58 (m, 1H, H-30), 4.19(q, J = 4.5, 3.2 Hz, 2H, H-50), 3.84 (d, J = 3.8 Hz, 1H, H-40), 2.48-2.30 (m, 2H, H-20); 31P NMR (162 MHz, D2O) d 9.48 (d,J = 19.2 Hz), 11.28 (d, J = 19.7 Hz), 22.40 to 22.71 (m). MS(ESI): m/z (%): 405.0 (100) [MPO3+H] 427.0 (33) [MPO3+Na+H]; HR/MS: calcd (m/z) for C9H11O14N2FNaP3 528.92080; found528.92099 [M+Na+H].

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6885 - 6890

41
[ 288-32-4 ]
[ 18162-48-6 ]
[ 50-91-9 ]
[ 129816-30-4 ]

Yield	Reaction Conditions	Operation in experiment
72%	With dmap; In N,N-dimethyl-formamide; at 0 - 20℃; for 1h;	To a stirred solution of 5-fluoro-20-deoxyuridine (1) (3.69 g,15 mmol), imidazole (3.06 g, 45 mmol) and DMAP (183 mg,1.5 mmol) in DMF (75 mL) was added t-butyldimethyl silyl chloride(2.94 g, 19.5 mmol) at 0 C and the mixture was allowed towarm to room temperature and stirring was continued for 1 h.Then saturated aqueous solution of ammonium chloride (150 mL)was added and the mixture was extracted with ethyl acetate(3 75 mL). The combined organic extracts were washed withwater (20 mL), dried over anhydrous magnesium sulfate, filteredand evaporated to dryness. The residue was purified by silica gelcolumn chromatography using chloroform-methanol (80:1, v/v)as eluent to afford pure 2 (yield: 3.89 g, 72%). 1H NMR (DMSOd6)d: 0.10 (s, 3H, SiCH3), 0.11 (s, 3H, SiCH3), 0.90 (s, 9H, t-Bu),2.03-2.48 (m, 2H, H-20 , H-200), 3.80-3.98 (m, 2H, H-50 , H-500),4.08-4.12 (m, 1H, H-40), 4.43-4.58 (m, 1H, H-30), 6.37 (pseudo t,1H, J = 6.5 Hz, H-10), 7.82 (d, 1H, JH-F = 6.2 Hz, H-6), 8.10 (br s, 1H,H-3). 13C NMR (DMSO-d6) d: 5.60 (Si(CH3)2), 18.35 (t-C), 25.86(C(CH3)3), 41.32 (C-20), 63.48 (C-50), 72.03 (C-30), 85.73 (C-10),87.87 (C-40), 124.43 (d, JC-F = 39.3 Hz, C-6), 140.53 (d,JC-F = 236.1 Hz, C-5), 149.34 (C-2), 157.47 (d, JC-F = 26.3 Hz, C-4).19F NMR (DMSO-d6) d: 166.28 (d, 1F, JH-F = 6.2 Hz). MS-ESI m/z:361 [M+H]+; 383 [M+Na]+; 399 [M+K]+; 359 [MH]; 395, 397[M+Cl]. Anal. Calcd for C15H25FN2O5Si: C, 49.98; H, 6.99; N, 7.77.Found: C, 50.03; H, 7.00; N, 7.78.

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 2330 - 2341

42
[ 58479-61-1 ]
[ 50-91-9 ]
1-((2R,4S,5R)-5-(((tert-butyldiphenylsilyl)oxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-5-fluoropyrimidine-2,4(1H,3H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With dmap; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	5?-O-TBDPS-floxuridine (1): Floxuridine (3.0 g, 12.2 mmol), DMAP (1.37 g), and DIPEA (4.8 ml) were dissolved in anhydrous DMF (30 ml). TBDPSCl (3.15 ml) was added into the solution slowly at room temperature. The reaction solution was allowed to stir overnight. Methanol (5 ml) was added. After 5 minutes, the solvent was evaporated under reduced pressure. The resulting residue was subjected to flash chromatography (MeOH/DCM=2%7%) to give the desired compound,
80%	With 1H-imidazole; In N,N-dimethyl-formamide; at 20℃; for 12h;	To a solution of commercially available Floxuridine (5-FdU) 1 (500.0 mg, 2.0 mmol) in DMF (5.0 mL), imidazole (207.4 mg, 13.1 mmol) was added portion wise followed by slow addition of TBDPSCl (669.9 mg, 2.4 mmol, 0.6 mL) at room temperature. The reaction was stirred for 12 h. The mixture was diluted with H2O and HCl (0.1 M) was added. The layers were separated. The aqueous phase was extracted with Et2O (2 x 60 mL). The combined organic layers were dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with MeOH in CH2Cl2 (0-7%) to give sylil ether 1a as a white solid (782.4 mg, 80% yield).1H NMR (400 MHz, CDCl3) delta 10.47 (s, 1H), 7.95 (d, J = 5.8 Hz, 1H), 7.67 (d, J = 7.0 Hz, 4H), 7.49 - 7.35 (m, 6H), 6.38 (t, J = 6.5 Hz, 1H), 4.52 (s, 1H), 4.08 (d, J = 1.9 Hz, 1H), 3.99 - 3.92 (m, 1H), 3.87 - 3.79 (m, 1H), 3.75 - 3.67 (m, 1H), 2.59 - 2.49 (m, 1H), 2.24 - 2.15 (m, 1H), 1.09 (s, 9H).13C NMR (101 MHz, CDCl3) delta 157.61, 157.35, 149.39, 141.88, 139.52, 135.69, 135.49, 132.46, 132.32, 130.19, 130.14, 128.02, 128.01, 124.39, 124.05, 87.64, 85.65, 71.91, 64.07, 41.16, 26.99, 19.19. HRMS (ESI+) m/z calcd for C25H30FN2O5Si [M+1]+: 485.1903, found: 485.1921.

Reference： [1]Patent: US9365604,2016,B2 .Location in patent: Page/Page column 37
[2]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 2652 - 2654

43
[ 50-91-9 ]
[ 5965-66-2 ]
[ 163218-40-4 ]

Yield	Reaction Conditions	Operation in experiment
18.8%	With β-galactosidase from Bacillus megaterium YZ08 In dimethyl sulfoxide at 35℃; Enzymatic reaction; regioselective reaction;

Reference： [1]Zhou, Youzhi; Chu, Jianlin; Zhang, Jinsong; Liu, Ke; He, Bingfang [RSC Advances, 2016, vol. 6, # 69, p. 64841 - 64846]

44
5'-DMT-5-fluoro-2'-deoxyuridine [ No CAS ]
[ 50-91-9 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid; In dichloromethane; at 5 - 10℃;Large scale;	10'g of the 5'-DMT-5-fluorodeoxyuridine was prepared by the above-mentioned method and added to 100 L of dichloromethane,Then add 5L trifluoroacetic acid,System closed insulation 5-10 stirring reaction,After two hours,HPLC monitoring to the main raw material is complete.After the reaction is complete, 50L of deionized water is added dropwise to the system, and the internal temperature does not exceed 10 C. After dripping, the lower layer is separated and the upper aqueous phase is adjusted to pH 6-7 with 6N NaOH. The aqueous phase was discarded with 20L dichloromethane and the dichloromethane was discarded. The aqueous phase was concentrated under reduced pressure at 45-55 C. After adding 100 L of acetonitrile to 70 C, 5 L of water was added and the solid was dissolved by stirring. , Remove the small amount of insoluble matter, and then 10-15 , heat crystallization for 10 hours, centrifugal, that was 5 - fluoride - deoxyuridine nucleoside, solid at 50-60 blast drying 12 hours after the powder, mix, HPLC Purity 99.99%, MS (ESI) m /z (M + H) 246.12, HPLC was consistent with the standard control.

Reference： [1]Patent: CN103897007,2017,B .Location in patent: Paragraph 0160; 0161; 0162; 0163; 0164; 0165

45
[ 1585199-32-1 ]
[ 50-91-9 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; In dichloromethane; at 25 - 30℃;Large scale;	10'g of the 5'-Tr-5-fluorodeoxyuridine obtained by the above-mentioned method was added to 100 L of dichloromethane,Then add 10L acetic acid,System closed insulation 25-30 stirring reaction,After two hours,HPLC monitoring to the main raw material is complete.After the reaction was complete, 50 L of deionized water was added dropwise to the system and the internal temperature did not exceed 30 C. After the dropwise addition, the lower layer was separated and the upper aqueous phase was adjusted to pH 6-7 with 6N NaOH. With 20L methylene chloride on the water phase extraction, dichloromethane phase, the water phase at 45-55 C under reduced pressure concentrated dry, then add 100L acetone heated to 60 , add 15L water, stirring dissolved solids, , Remove a small amount of insoluble matter, and then 5-10 , 10 minutes of thermal crystallization, centrifugation, that was 5 - fluoro - deoxyuridine nucleoside, solid at 50-60 blast drying 12 hours after the powder, mix, HPLC Purity 99.99%, MS (ESI) m /z (M + H) 246.20, HPLC consistent with the standard control.

Reference： [1]Patent: CN103897007,2017,B .Location in patent: Paragraph 0166; 0167; 0168; 0169; 0170; 0171

46
3',5'-di-TBDMS-5-fluoro-2'-deoxyuridine [ No CAS ]
[ 50-91-9 ]

Yield	Reaction Conditions	Operation in experiment
	With tetrabutyl ammonium fluoride; In dichloromethane; at 25 - 30℃;Large scale;	The 10 ', 5'-di-TBDMS-5-fluorodeoxyuridine was prepared by adding 10Kg of the above method to100 L of dichloromethane,Then add 10L tetrabutylammonium fluoride,System closed insulation 25-30 stirring reaction,After two hours,HPLC monitoring to the main raw material is complete.After the reaction is complete, 50 L of deionized water is added dropwise to the system, and the internal temperature does not exceed 20 C. After dripping, the lower layer is separated and the upper aqueous phase is adjusted to pH 6-7 with 6N HCl. The aqueous phase was discarded with 20 L of dichloromethane and the aqueous phase was discarded at 45-55 C. After adding 100 L of ethanol to 70 C, add 5 L of water, stir the dissolved solids, , Remove a small amount of insoluble matter, and then 5-10 , 10 minutes of thermal crystallization, centrifugation, that was 5 - fluoro - deoxyuridine nucleoside, solid at 50-60 blast drying 12 hours after the powder, mix, HPLC Purity 99.99%, MS (ESI) m / z (M +H) 246.25, HPLC was consistent with the standard control.

Reference： [1]Patent: CN103897007,2017,B .Location in patent: Paragraph 0172; 0173; 0174; 0175; 0176; 0177

47
[ 54202-96-9 ]
[ 50-91-9 ]

Yield	Reaction Conditions	Operation in experiment
	With tetrabutyl ammonium fluoride; In dichloromethane; at 25 - 30℃;Large scale;	10Kg of the 3 ', 5'-di-TMS-5-fluorodeoxyuridine was prepared by the above-mentioned method and added to 100 L of dichloromethanein,Then add 5L tetrabutylammonium fluoride,System closed insulation 25-30 stirring reaction,After two hours,HPLC monitoring to the main raw material is complete.After the reaction is complete, 50 L of deionized water is added dropwise to the system, and the internal temperature does not exceed 20 C. After dripping, the lower layer is separated and the upper aqueous phase is adjusted to pH 6-7 with 6N HCl. The aqueous phase was discarded with 20 L of dichloromethane and the dichloromethane was discarded. The aqueous phase was concentrated under reduced pressure at 45-55 C. After adding 70 L of ethanol to 70 C, 5 L of water was added and the solid was dissolved by stirring. , Remove a small amount of insoluble matter, and then 5-10 , 10 minutes of thermal crystallization, centrifugation, that was 5 - fluoro - deoxyuridine nucleoside, solid at 50-60 blast drying 12 hours after the powder, mix, HPLC Purity 99.99%, MS (ESI) m / z (M +H) 246.15, HPLC was consistent with the standard control.

Reference： [1]Patent: CN103897007,2017,B .Location in patent: Paragraph 0178; 0179; 0180; 0181; 0182; 0183

48
[ 76-83-5 ]
[ 124-63-0 ]
[ 50-91-9 ]
[ 101039-89-8 ]

Yield	Reaction Conditions	Operation in experiment
95%		In a round-bottomed flask equipped with a reflux condenser and CaCl2tube, 5-fluoro-20-deoxyuridine (0.90 g, 0.36mmol) was coevaporated twotimes with anhydrous pyridine and next dissolved in pyridine (18mL).To the solution trityl chloride (1.25 g, 1.2 eq) was added and the mixturewas being stirred at 100 C for 30min.[38] After that the mixture wascooled to room temperature, followed by addition of the methanesulfonylchloride (0.44mL, 1.5 eq) and the mixture was stirred at room temperaturefor 2 h (it was possible to carry out the reaction in the refrigeratorovernight). Then chloroform was added to the reaction mixture and itwas extracted with 5% aqueous solution of sodium bicarbonate. Theorganic layer was dried over anhydrous magnesium sulfate, filtered andevaporated to dryness. To the residue was added toluene and the mixturewas evaporated to remove traces of pyridine. The crude compound 6 wasdried in a vacuum exsiccator over P2O5 (a white powder, yield:1.96 g, 95%).

Reference： [1]Nucleosides, nucleotides and nucleic acids,2019

49
[ 41864-22-6 ]
[ 93930-15-5 ]
[ 50-91-9 ]
C₂₅H₂₉FN₂O₁₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%		Fluorouracil(123.1 mg) and 1,1'-carbonyldiimidazole (81.1 mg) were dissolved in 10 mL of dichloromethane, and the mixture was stirred at room temperature for 2 hours, then 10 mL of deionized water was added, and the mixture was extracted with 50 mL of dichloromethane. The organic layer was washed three times with deionized water (10 mL x 3), dried and concentrated under reduced pressure to give a hydroxy-activated fluorourea intermediate.The intermediate product (68.2 mg) was added to 10 mL of methanol dissolved in hydroxymethyl parthenolide (52.8 mg) at room temperature.Further, a catalyst of triethylamine (200 muL) was added, and the reaction was stirred for 48 hours.10 mL of deionized water was added and extracted with dichloromethane. The organic phase was washed three times with deionized water (10 mL×3), then washed with 10 mL of saturated NaCI solution, dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to give crude product, then chloroform/methanol (volume ratio = 20) :1) As an eluent, the crude product was purified by column chromatography, and the solvent was removed by rotary evaporation to give the desired product 59.8 mg, yield 57%.

Reference： [1]Patent: CN110075314,2019,A .Location in patent: Paragraph 0044-0046

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	50-91-9	MDL No. :	MFCD00006530
Formula :	C₉H₁₁FN₂O₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ODKNJVUHOIMIIZ-RRKCRQDMSA-N
M.W :	246.19	Pubchem ID :	5790
Synonyms :	5-Fluorouracil 2'-deoxyriboside;5-FDU;FUdR. WR138720.;FDUR;fluoruridine deoxyribose. FUDF. 5FUDR;fluorouridine deoxyribose;fluorodeoxyuridine;floxuridin;NSC 26740;5-FUDR;5-Fluorodeoxyuridine;FdUrd;NSC 27640	Chemical Name :	5-Fluoro-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione

Num. heavy atoms :	17
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.56
Num. rotatable bonds :	2
Num. H-bond acceptors :	6.0
Num. H-bond donors :	3.0
Molar Refractivity :	53.07
TPSA :	104.55 Å²

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) :	-8.63 cm/s

[ CAS No. 50-91-9 ] {[proInfo.proName]}

Quality Control of [ 50-91-9 ]

Related Doc. of [ 50-91-9 ]

Product Details of [ 50-91-9 ]

Calculated chemistry of [ 50-91-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 50-91-9 ]

Application In Synthesis of [ 50-91-9 ]

[ 50-91-9 ] Synthesis Path-Upstream 1~2

[ 50-91-9 ] Synthesis Path-Downstream 1~49

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Log Po/w (iLOGP) :	0.85
Log Po/w (XLOGP3) :	-1.16
Log Po/w (WLOGP) :	-1.59
Log Po/w (MLOGP) :	-1.44
Log Po/w (SILICOS-IT) :	-0.07
Consensus Log Po/w :	-0.68

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

Log S (ESOL) :	-0.76
Solubility :	42.3 mg/ml ; 0.172 mol/l
Class :	Very soluble
Log S (Ali) :	-0.54
Solubility :	70.5 mg/ml ; 0.286 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.34
Solubility :	113.0 mg/ml ; 0.457 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.61

Signal Word:	Danger	Class:	6.1
Precautionary Statements:	P264-P270-P301+P310+P330-P405-P501	UN#:	2811
Hazard Statements:	H301	Packing Group:	Ⅲ
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling