10212-20-1

Usage

Uses

Used in Antiviral Applications:
4-Amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one is used as an antiviral agent for inhibiting the replication and spread of various viruses, including the hepatitis C virus and the Borna Disease virus. Its potent inhibitory effects on viral replicons in Huh-7 cells demonstrate its potential as a therapeutic agent in combating viral infections.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 4-Amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one is used as a key intermediate in the synthesis of antiviral drugs. Its unique chemical properties and antiviral activity make it a valuable component in the development of new medications to treat viral diseases.
Used in Research and Development:
4-Amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one is also used in research and development for studying the mechanisms of viral replication and the development of resistance to antiviral drugs. Its potent inhibitory effects on viral replicons provide valuable insights into the design of new antiviral agents and strategies for combating viral infections.

InChI:InChI=1/C9H12FN3O4/c10-6-7(15)4(3-14)17-8(6)13-2-1-5(11)12-9(13)16/h1-2,4,6-8,14-15H,3H2,(H2,11,12,16)/t4-,6?,7-,8-/m1/s1

Synthetic route

9-<2-deoxy-2-fluoro-3,5-di-O-(tetrahydropyran-2-yl)-β-D-ribofuranosyl>cytosine (157024-78-7) → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions	Yield
With ethanol; pyridinium p-toluenesulfonate for 24h; Heating;	66%

3',5'-Di-O-benzoyl-2'-desoxy-2'-fluorcytidin → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions	Yield
With ammonium hydroxide at 50℃;	56%

Acetic acid (2R,3R,4R,5R)-2-acetoxymethyl-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-4-fluoro-tetrahydro-furan-3-yl ester → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions	Yield
With N,N-dimethyl-ethanamine In methanol at 50℃; for 24h; Yield given;

cyclocitidine (31698-14-3) → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions	Yield
With potassium fluoride

3’,5’-O-acetyl-2’-deoxy-2’-fluorouridine (10212-13-2) → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: (PhO)2POCl, Et3N / acetonitrile / 1.5 h / Ambient temperature 2: 32percent aq. NH3 / dioxane / 0.33 h 3: EtNMe2 / methanol / 24 h / 50 °C View Scheme

2'-deoxy-2'-fluorouridine (56287-17-3, 69123-94-0, 784-71-4) → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 92 percent / pyridine / 2 h / Ambient temperature 2: (PhO)2POCl, Et3N / acetonitrile / 1.5 h / Ambient temperature 3: 32percent aq. NH3 / dioxane / 0.33 h 4: EtNMe2 / methanol / 24 h / 50 °C View Scheme

Acetic acid (2R,3R,4R,5R)-2-acetoxymethyl-4-fluoro-5-[4-(3-nitro-[1,2,4]triazol-1-yl)-2-oxo-2H-pyrimidin-1-yl]-tetrahydro-furan-3-yl ester (196928-90-2) → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 32percent aq. NH3 / dioxane / 0.33 h 2: EtNMe2 / methanol / 24 h / 50 °C View Scheme

2,2'-Anhydrouridine (3736-77-4) → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions

Yield

Multi-step reaction with 5 steps 1: 87 percent / p-TsOH / dimethylformamide / 2.5 h / 0 °C 2: 25.1 g / 1 N aq. NaOH / methanol / 1.5 h / Ambient temperature 3: 57 percent / diethylaminosulfur trifluoride (DAST), pyridine / CH2Cl2 / 3 h / Heating 4: 1.) 4-chlorophenyl phosphorodichloridate, 1,2,4-triazole, pyridine, 2.) conc. NH4OH / 1.) RT, 2 d, 2.) dioxane, RT, 1 d 5: 66 percent / pyridinium p-toluenesulfonate (PPTS), C2H5OH / 24 h / Heating View Scheme

3',5'-di-O-(tetrahydropyran-2-yl)-2,2'-O-cyclouridine (351523-07-4) → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions

Yield

Multi-step reaction with 4 steps 1: 25.1 g / 1 N aq. NaOH / methanol / 1.5 h / Ambient temperature 2: 57 percent / diethylaminosulfur trifluoride (DAST), pyridine / CH2Cl2 / 3 h / Heating 3: 1.) 4-chlorophenyl phosphorodichloridate, 1,2,4-triazole, pyridine, 2.) conc. NH4OH / 1.) RT, 2 d, 2.) dioxane, RT, 1 d 4: 66 percent / pyridinium p-toluenesulfonate (PPTS), C2H5OH / 24 h / Heating View Scheme

9-<3,5-di-O-(tetrahydropyran-2-yl)-β-D-arabinofuranosyl>uracil (157024-75-4) → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 57 percent / diethylaminosulfur trifluoride (DAST), pyridine / CH2Cl2 / 3 h / Heating 2: 1.) 4-chlorophenyl phosphorodichloridate, 1,2,4-triazole, pyridine, 2.) conc. NH4OH / 1.) RT, 2 d, 2.) dioxane, RT, 1 d 3: 66 percent / pyridinium p-toluenesulfonate (PPTS), C2H5OH / 24 h / Heating View Scheme

9-<2-deoxy-2-fluoro-3,5-di-O-(tetrahydropyran-2-yl)-β-D-ribofuranosyl>uracil (157024-77-6) → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) 4-chlorophenyl phosphorodichloridate, 1,2,4-triazole, pyridine, 2.) conc. NH4OH / 1.) RT, 2 d, 2.) dioxane, RT, 1 d 2: 66 percent / pyridinium p-toluenesulfonate (PPTS), C2H5OH / 24 h / Heating View Scheme

3',5'-Di-o-benzoyl-2'-desoxy-2'-fluoruridin → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 73 percent / p-Cl-C6H4-OP(O)Cl2 2: 82 percent / conc. aq. NH3 / dioxane / 1 h 3: 56 percent / conc. NH3 / 50 °C View Scheme

4-Tetrazolo-3',5'-di-O-benzoyl-2'-fluor-1(2H)-pyrimidinon (128963-08-6) → 2'-deoxy-2'-fluorocytidine (10212-20-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / conc. aq. NH3 / dioxane / 1 h 2: 56 percent / conc. NH3 / 50 °C View Scheme

benzoic acid anhydride (93-97-0) + 2'-deoxy-2'-fluorocytidine (10212-20-1) → N4-benzoyl-2-deoxy-2-fluorocytidine (146954-76-9)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃;	100%
In N,N-dimethyl-formamide at 20℃;	100%
In N,N-dimethyl-formamide	92%

2'-deoxy-2'-fluorocytidine (10212-20-1) → 5-bromo-2'-deoxy-2'-fluorocytidine

Conditions	Yield
With pyridine; bromine In tetrachloromethane at 20℃; for 0.416667h;	84%

tert-butyldimethylsilyl chloride (18162-48-6) + 2'-deoxy-2'-fluorocytidine (10212-20-1) → 2'-deoxy-2'-fluoro-5'-O-TBDMS-cytidine (1246253-27-9)

Conditions	Yield
With pyridine at 20℃;	82%
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 4h; regioselective reaction;	77%
With pyridine at 20℃; for 16h; Cooling with ice;
With pyridine

2'-deoxy-2'-fluorocytidine (10212-20-1) → 5-iodo-2'-deoxy-2'-(R)-fluoro-cytidine (80791-93-1)

Conditions	Yield
With iodine; 3-chloro-benzenecarboperoxoic acid In N,N-dimethyl-formamide at 20℃; for 7h;	67%
With Iodine monochloride In methanol at 50℃; for 4h;	39%
With iodine; iodic acid; acetic acid In tetrachloromethane; water at 45℃; for 4h; Iodination;

2'-deoxy-2'-fluorocytidine (10212-20-1) → 2'-deoxy-2'-fluoro-N4-hydroxycytidine

Conditions	Yield
With hydroxylamine hydrochloride; sodium hydroxide In water at 55℃; for 16h; pH=5; Inert atmosphere;	47%
With hydroxylamine hydrochloride In water at 55℃; for 16h; pH=5; Sealed tube; Inert atmosphere;	91 mg

2'-deoxy-2'-fluorocytidine (10212-20-1) → 5-chloro-2'-deoxy-2'-fluorocytidine

Conditions	Yield
With benzoyl chloride; 3-chloro-benzenecarboperoxoic acid In N,N-dimethyl-formamide at 20℃; for 0.5h;	24%

acetyl chloride (75-36-5) + 2'-deoxy-2'-fluorocytidine (10212-20-1) → Acetic acid (2R,3R,4R,5R)-2-acetoxymethyl-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-4-fluoro-tetrahydro-furan-3-yl ester; hydrochloride

Conditions	Yield
With hydrogenchloride at 90 - 95℃; for 0.5h;

2'-deoxy-2'-fluorocytidine (10212-20-1) + 2,6-diaminopurine (1904-98-9) → 2,6-diamino-9-(2-deoxy-2-fluoro-β-D-ribofuranosyl)-9H-purine (134444-47-6)

Conditions	Yield
With E. coli BMT-4D Substitution;

2'-deoxy-2'-fluorocytidine (10212-20-1) → N-{3-[4-Amino-1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-2-oxo-1,2-dihydro-pyrimidin-5-yl]-prop-2-ynyl}-2,2,2-trifluoro-acetamide

Conditions	Yield
Multi-step reaction with 2 steps 1: HIO3; I2; AcOH / CCl4; H2O / 4 h / 45 °C 2: CuI; (Ph3P)4P; Et3N / dimethylformamide / 16 h View Scheme

2'-deoxy-2'-fluorocytidine (10212-20-1) → 2'-deoxy-2'-fluoroguanosine (78842-13-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: E. coli BMT-4D/1A 2: ADase View Scheme

2'-deoxy-2'-fluorocytidine (10212-20-1) → N4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-fluoro-2'-deoxycytidine (146954-77-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 92 percent / dimethylformamide 2: 87 percent / Et3N / pyridine View Scheme

2'-deoxy-2'-fluorocytidine (10212-20-1) → N4-benzoyl-2'-deoxy-2'-fluoro-5'-O-(4,4'-dimethoxytrityl)cytidine 3'-(β-cyanoethyl N,N-diisopropylphosphoramidite) (161442-19-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 92 percent / dimethylformamide 2: 87 percent / Et3N / pyridine 3: 90 percent / (i-Pr)2EtN / CH2Cl2 View Scheme

2'-deoxy-2'-fluorocytidine (10212-20-1) → 3',5'-di-O-acetyl-2'-deoxy-2'-fluoro-5-iodocytosine hydrochloride (83966-99-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) HCl / 0.5 h / 90 - 95 °C 2: I2, HIO3, AcOH / H2O; CCl4 / 24 h / 50 - 55 °C View Scheme

2'-deoxy-2'-fluorocytidine (10212-20-1) → N4-benzoyl-2-deoxy-2-fluorocytidine (146954-76-9)

2'-deoxy-2'-fluorocytidine (10212-20-1) + tert-butylchlorodiphenylsilane (58479-61-1) → C25H30FN3O4Si

Conditions	Yield
With dmap; triethylamine In N,N-dimethyl-formamide at 0 - 50℃; for 12h;

Upstream product

• 128963-08-6 4-Tetrazolo-3',5'-di-O-benzoyl-2'-fluor-1(2H)-pyrimidinon 
• 157024-77-6 9-<2-deoxy-2-fluoro-3,5-di-O-(tetrahydropyran-2-yl)-β-D-ribofuranosyl>uracil 
• 157024-75-4 9-<3,5-di-O-(tetrahydropyran-2-yl)-β-D-arabinofuranosyl>uracil 
• 351523-07-4 3',5'-di-O-(tetrahydropyran-2-yl)-2,2'-O-cyclouridine 
• 3736-77-4 2,2'-Anhydrouridine 
• 196928-90-2 Acetic acid (2R,3R,4R,5R)-2-acetoxymethyl-4-fluoro-5-[4-(3-nitro-[1,2,4]triazol-1-yl)-2-oxo-2H-pyrimidin-1-yl]-tetrahydro-furan-3-yl ester 
• 56287-17-3 2'-deoxy-2'-fluorouridine 
• 10212-13-2 3’,5’-O-acetyl-2’-deoxy-2’-fluorouridine 
• 31698-14-3 cyclocitidine 
• 157024-78-7 9-<2-deoxy-2-fluoro-3,5-di-O-(tetrahydropyran-2-yl)-β-D-ribofuranosyl>cytosine 

Downstream Products

• 146954-76-9 N4-benzoyl-2-deoxy-2-fluorocytidine 
• 78842-13-4 2'-deoxy-2'-fluoroguanosine 
• 1048374-12-4 (2R,3R,4R,5R)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-yl benzoate 
• 1048374-14-6 C₂₆H₂₅FN₃O₈P 
• 1244969-83-2 3-[5-0-(4,4'-dimethoxytrityl)-(2-fluoro-2-deoxy-β-D-erythro-pentofuranosyl)]pyrido[2,3-d]pyrimidine-2,7(8H)-dione 3'-O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite 
• 1188531-07-8 C₃₃H₃₀FN₃O₇ 
• 182495-82-5 O₅'-dimethoxytrityl-N₄-benzoyl-5-methyl-2'-deoxy-2'-(R)-fluorocytidine 

Relevant academic research and scientific papers

Synthesis and hypnotic and anti-human immunodeficiency virus-1 activities of N3-substituted 2'-deoxy-2'-fluorouridines

Reaction of 9-[3,5-di-O-(tetrahydropyran-2-yl)-β-D- arabinofuranosyl]uracil (2) with diethylaminosulfur trifluoride in the presence of pyridine afforded 2'-deoxy-2'-flouroriboside 3a, from which 2'- deoxy-2'-fluorocytidine (14b) has been synthesized in good yield. Compound 3a was deprotected and subsequently treated with various benzyl halides or 2- chloro-4-fluoroacetophenone to give corresponding N3-substituted 2'-deoxy- 2'-fluorouridines 5a-c and 6. Compounds 5a-c, as well as 6, showed weak hypnotic activity in mice. Compound 4b showed moderate antiviral activity against human immunodeficiency virus-1 but 3b, 5a-c, and 6 were virtually inactive.

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Based on the discovery of β-D-2′-deoxy-2′-fluorocytidine as a potent anti-hepatitis C virus (HCV) agent, a series of β-D- and L-2′-deoxy-2′-fluororibonucleosides with modifications at 5 and/or 4 positions were synthesized and evaluated for their in vitro activity against HCV and bovine viral diarrhea virus (BVDV). The introduction of the 2′-fluoro group was achieved by either fluorination of 2,2′-anhydronucleosides with hydrogen fluoride-pyridine or potassium fluoride, or a fluorination of arabinonucleosides with DAST. Among the 27 analogues synthesized, only the 5-fluoro compounds, namely β-D-2′- deoxy-2′,5-difluorocytidine (5), had anti-HCV activity in the subgenomic HCV replicon cell line, and inhibitory activity against ribosomal RNA. As β-D-N4-hydroxycytidine (NHC) had previously shown potent anti-HCV activity, the two functionalities of the N4-hydroxyl and the 2′-fluoro were combined into one molecule, yielding β-D-2′- deoxy-2′-fluoro-N4-hydroxycytidine (12). However, this nucleoside showed neither anti-HCV activity nor toxicity. All the L-forms of the analogues were devoid of anti-HCV activity. None of the compounds showed anti-BVDV activity, suggesting that the BVDV system cannot reliably predict anti-HCV activity in vitro. Copyright Taylor & Francis, Inc.

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