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Chemical Structure| 161599-46-8 Chemical Structure| 161599-46-8
Chemical Structure| 161599-46-8

2',3'-Di-O-acetyl-5'-deoxy-5-fluoro-D-cytidine

CAS No.: 161599-46-8

Synonyms: 5'-Deoxy-2',3'-di-O-acetyl-5-fluorocytidine; 2',3'-Di-O-acetyl-5'-deoxy-5-fluorocytidine

4.5 *For Research Use Only !

Cat. No.: A147683 Purity: 95%

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Product Details of [ 161599-46-8 ]

CAS No. :161599-46-8
Formula : C13H16FN3O6
M.W : 329.28
SMILES Code : C[C@@H]1[C@H]([C@H]([C@H](N2C(N=C(C(F)=C2)N)=O)O1)OC(C)=O)OC(C)=O
Synonyms :
5'-Deoxy-2',3'-di-O-acetyl-5-fluorocytidine; 2',3'-Di-O-acetyl-5'-deoxy-5-fluorocytidine
MDL No. :MFCD07369302
InChI Key :NWJBWNIUGNXJGO-RPULLILYSA-N
Pubchem ID :11809635

Safety of [ 161599-46-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis [ 161599-46-8 ]

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

  • Upstream synthesis route of [ 161599-46-8 ]
  • Downstream synthetic route of [ 161599-46-8 ]

[ 161599-46-8 ] Synthesis Path-Upstream   1~3

  • 1
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  • [ 162204-20-8 ]
YieldReaction ConditionsOperation in experiment
94.2% With potassium phosphate In dichloromethane; isopropyl alcohol at 0 - 25℃; for 4 h; Inert atmosphere The compound of formula IV (100 g, 0.30 mol), K3PO4 (95.5 g, 0.45 mol), solvent (800 mL isopropanol: dichloromethane = 1.0:2.0, volume ratio) into the reaction flask, nitrogen protection, cooled to 0-10 ° C, was added dropwise under stirring n-pentyl chloroformate (54.2g, 0.36 mol) solution (200 mL, isopropanol: dichloromethane = 1.0: 2.0, volume ratio). The temperature of the dropping process was controlled at 0-10 ° C. and completed in 1 h. After the dropping, the temperature was naturally raised to 20-25 ° C and reacted for 4 hours. The reaction was completed until the raw material was completely detected. 400 mL of purified water was added to the feed solution, stirred for half an hour and then separated. The organic layer was washed once with 400 mL of hydrochloric acid solution (1 mol / L), the combined aqueous layers were extracted with 200 mL of dichloromethane, and the organic layers were combined. Washed once with 400 mL saturated brine, once with 400 mL of 5percent aqueous sodium bicarbonate, once with 400 mL of saturated brine and dried over anhydrous sodium sulfate. The desiccant was removed by filtration. The filtrate was concentrated to dryness under reduced pressure at 40 ° C. The residue was beaten with 80 mL of ether, filtered and dried to give a white solid (125.3 g, 0.28 mol, 94.2percent). HPLC content was 99.09percent.
93% With pyridine In dichloromethane at 0℃; for 1 h; 2 ', 3'-di-O-acetyl-5'-deoxy-5-fluorocytidine (8)48.6 mmol) was dissolved in dichloromethane (160 ml)Pyridine (16 ml) was added, cooled to 0 ° C, n-amyl chloroformate (9) (16 g) was added, stirred at 0 ° C for 1 h,The organic phase was washed with water (50 ml), dried over anhydrous magnesium sulfate, evaporated to dryness under reduced pressure, and the residue was taken up by the addition of methylene chloride (100 ml). The residue was extracted with dichloromethane Ethyl acetate (16 ml) was added, and petroleum ether (160 ml) was added dropwise. The mixture was stirred until the solid precipitated completely and filtrated to give a solid compound of 2 ', 3'-di-O-acetyl-5'-deoxy- - [(pentyloxy) carbonyl] cytidine (10) (20 g, 93percent).
90.6% With dmap; potassium carbonate In dichloromethane at 5℃; for 0.75 h; In an ice bath, the temperature is controlled at 5°C.Slowly dropping n-amyl chloroformate (21.5 mmol) into K2CO3 (21.7 mmol),Dimethylaminopyridine (2.46 mmol)The reaction was incubated for 45 min with a solution of 2',3'-di-O-acetyl-5'-deoxy-5-fluorocytidine (14.5 mmol) in dichloromethane (30 mL).The mixture was filtered, and the filtrate was washed successively with 0.2 M hydrochloric acid (10 mL), water (10 mL) and saturated brine (10 mL), and dried over anhydrous sodium sulfate.The solvent was removed under reduced pressure to give a white solid (6.1 g, yield 90.6percent).
2.55 g With pyridine In dichloromethaneReflux Place 2.00 g (6 mmol; 1.0 eq.) of 2',3'-di-O-acetyl-5'-deoxy-5-fluorocytydine and 12 mL ofdichloromethane in a 100 mL 3-neck round bottom flask equipped with a dropping funnel, reflux condenser, and magnetic stirring bar. After solid dissolution, 0.7 mL (9 mmol; 1.5 eq.) of pyridine was added. Next, 1.1 mL of n-pentyl chloroformate was placed in the dropping funnel and addeddrop-by-drop to the vigorously stirred starting solution, while maintaining the reacting mixture under soft reflux. When the n-pentyl chloroformate addition was completed, the solution was stirred for 1 h and then cooled to room temperature, poured into the separation funnel, and washed with 10 mLof aq. CuSO4, 10 mL of brine, and 10 mL of water, then dried over MgSO4. The clear solution was evaporated twice from 5 mL of the toluene solution giving 2.55 g of 1 as a white solid.

References: [1] Patent: CN106478751, 2017, A, . Location in patent: Paragraph 0010; 0022; 0039; 0040; 0041; 0042; 0043-0060.
[2] Patent: CN102212095, 2016, B, . Location in patent: Paragraph 0062; 0063; 0064.
[3] Patent: CN104744537, 2018, B, . Location in patent: Paragraph 0018; 0019; 0020; 0022; 0025; 0028.
[4] Tetrahedron Letters, 2015, vol. 56, # 43, p. 5909 - 5913.
[5] Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 7, p. 1697 - 1706.
[6] Patent: WO2008/131062, 2008, A2, . Location in patent: Page/Page column 37.
[7] Patent: US2008/300399, 2008, A1, . Location in patent: Page/Page column 1; 4.
[8] Patent: US2008/300399, 2008, A1, . Location in patent: Page/Page column 1; 4-5.
[9] Patent: WO2009/42613, 2009, A1, . Location in patent: Page/Page column 56.
[10] Patent: US2009/209754, 2009, A1, . Location in patent: Page/Page column 8.
[11] Patent: WO2010/65586, 2010, A2, . Location in patent: Page/Page column 9; 24.
[12] Patent: US2011/21769, 2011, A1, . Location in patent: Page/Page column 3; 5-6.
[13] European Journal of Medicinal Chemistry, 2012, vol. 54, p. 690 - 696.
[14] Organic Process Research and Development, 2016, vol. 20, # 3, p. 609 - 614.
[15] Patent: CN103570781, 2016, B, . Location in patent: Paragraph 0012; 0036; 0037.
[16] Molecules, 2018, vol. 23, # 1, .
  • 2
  • [ 71-41-0 ]
  • [ 530-62-1 ]
  • [ 161599-46-8 ]
  • [ 162204-20-8 ]
YieldReaction ConditionsOperation in experiment
91.6% at 20℃; for 4 h; To a 1000 ml reaction flask, 600 ml of methylene chloride, 84.8 g of 2',3'-di-O-acetyl-5'-deoxy-5-fluorocytidine, 48.6 g of carbonyldiimidazole, and 25.2 g of n-pentanol were charged. The reaction was carried out at 20° C. for 4 hours. The end of the reaction was monitored by TLC (developer, dichloromethane:methanol=20:1). 220 ml of 10percent hydrochloric acid solution was added to the reaction mixture. The organic layer was separated, washed with 220 ml of purified water, and separated. The organic layer was controlled at a bath temperature of 60° C., and the organic layer was concentrated under reduced pressure to dryness. To the residue was added 160 ml of ethyl acetate and 320 ml of n-hexane was stirred for 30 minutes. The temperature was lowered to 10° C. or lower, and suction filtration was started to obtain a white solid. °C, 104.8 g of 2',3'-di-O-acetyl-5'-deoxy-5-fluoro-N4-n-pentyloxycarbonyl cytidine was dried, yielding 91.6percent, purity 99.7percent.
References: [1] Patent: CN107936075, 2018, A, . Location in patent: Paragraph 0024-0026.
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References: [1] European Journal of Medicinal Chemistry, 2012, vol. 54, p. 690 - 696.
 

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