10212-20-1

Basic information

• Product Name: 4-Amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
• Synonyms: 4-amino-1-[(2r,3r,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one;4-AMINO-1-((2R,3R,4R,5R)-3-FLUORO-4-HYDROXY-5-HYDROXYMETHYL-TETRAHYDRO-FURAN-2-YL)-1H-PYRIMIDIN-2-ONE;2'-FLUORO-D-CYTIDINE;2'-DEOXY-2'-FLUOROCYTIDINE;2'-FC;2'-FLUORO-2'-DEOXYCYTIDINE;2'-DEOXY-2'-FLUOROCYTIDINE(2'-FLUORO-2'- DEOXYCYTIDINE, 2'-FC);2'-Deoxy-2'-fluoro-D-cytidine
• CAS NO: 10212-20-1
• Molecular Formula: C₉H₁₂FN₃O₄
• Molecular Weight: 245.21
• EINECS: 1806241-263-5
• Product Categories: Biochemistry;Nucleosides and their analogs;Nucleosides, Nucleotides & Related Reagents
• Mol File: 10212-20-1.mol

Chemical Properties

• Melting Point: 167 °C
• Boiling Point: 500.1 °C at 760 mmHg
• Flash Point: 256.2 °C
• Appearance: White to Off-white/Powder
• Density: 1.82 g/cm³
• Refractive Index: 80 ° (C=1, MeOH)
• Storage Temp.: 2-8°C
• Solubility: Soluble in DMSO, Methanol.
• PKA: 12.84±0.70(Predicted)
• CAS DataBase Reference: 4-Amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one(10212-20-1)
• EPA Substance Registry System: 4-Amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one(10212-20-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• Hazardous Substances Data: 10212-20-1(Hazardous Substances Data)

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

• 157024-78-7 9-<2-deoxy-2-fluoro-3,5-di-O-(tetrahydropyran-2-yl)-β-D-ribofuranosyl>cytosine 
• 31698-14-3 cyclocitidine 
• 56287-17-3 2'-deoxy-2'-fluorouridine 
• 128963-08-6 4-Tetrazolo-3',5'-di-O-benzoyl-2'-fluor-1(2H)-pyrimidinon 
• 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 
• 10212-13-2 3’,5’-O-acetyl-2’-deoxy-2’-fluorouridine 
• 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 

Downstream Products

• 146954-76-9 N4-benzoyl-2-deoxy-2-fluorocytidine 
• 134444-47-6 2,6-diamino-9-(2-deoxy-2-fluoro-β-D-ribofuranosyl)-9H-purine 
• 80791-93-1 5-iodo-2'-deoxy-2'-(R)-fluoro-cytidine 
• 78842-13-4 2'-deoxy-2'-fluoroguanosine 
• 146954-77-0 N⁴-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-fluoro-2'-deoxycytidine 
• 161442-19-9 N⁴-benzoyl-2'-deoxy-2'-fluoro-5'-O-(4,4'-dimethoxytrityl)cytidine 3'-(β-cyanoethyl N,N-diisopropylphosphoramidite) 
• 159414-97-8 4-N-acetyl-2'-fluoro-2'-deoxycytidine 
• 1244969-69-4 C₃₀H₂₄FN₃O₇ 
• 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 
• 1246253-29-1 3'-O-N₄-bis(4-methoxytrityl)-2'-deoxy-2'-fluorocytidine 
• 1246253-30-4 3'-O-N₄-bis(4-methoxytrityl)-5'-C,5'-O-didehydro-2'-deoxy-2'-fluorocytidine 
• 1445379-41-8 C₅₀H₄₆FN₃O₇ 
• 1445381-83-8 C₃₇H₄₄FN₅O₆Si 

Relevant articles and documents

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.

Antisense modulation of CD40 ligand expression

Antisense compounds, compositions and methods are provided for modulating the expression of CD40 ligand. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CD40 ligand. Methods of using these compounds for modulation of CD40 ligand expression and for treatment of diseases associated with expression of CD40 ligand are provided.

Modulation of DC-SIGN expression

Compounds, compositions and methods are provided for modulating the expression of DC-SIGN. The compositions comprise oligonucleotides, targeted to nucleic acid encoding DC-SIGN. Methods of using these compounds for modulation of DC-SIGN expression and for diagnosis and treatment of diseases and conditions associated with expression of DC-SIGN are provided.

Synthesis and in vitro anti-HCV activity of β-D- and L-2′-deoxy-2′-fluororibonucleosides

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.

Antisense modulation of polo-like kinase expression

Antisense compounds, compositions and methods are provided for modulating the expression of polo-like kinase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding polo-like kinase. Methods of using these compounds for modulation of polo-like kinase expression and for treatment of diseases associated with expression of polo-like kinase are provided.

Modulation of CEACAM1 expression

Compounds, compositions and methods are provided for modulating the expression of CEACAM1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding CEACAM1. Methods of using these compounds for modulation of CEACAM1 expression and for diagnosis and treatment of disease associated with expression of CEACAM1 are provided.

Modulation of diacylglycerol acyltransferase 1 expression

Compounds, compositions and methods are provided for modulating the expression of diacylglycerol acyltransferase 1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding diacylglycerol acyltransferase 1. Methods of using these compounds for modulation of diacylglycerol acyltransferase 1 expression and for diagnosis and treatment of disease associated with expression of diacylglycerol acyltransferase 1 are provided.

Antisense modulation of PPP3CB expression

Antisense compounds, compositions and methods are provided for modulating the expression of PPP3CB. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PPP3CB. Methods of using these compounds for modulation of PPP3CB expression and for treatment of diseases associated with expression of PPP3CB are provided.

Antisense modulation of Notch (Drosophila) homolog 4 expression

Antisense compounds, compositions and methods are provided for modulating the expression of Notch (Drosophila) homolog 4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Notch (Drosophila) homolog 4. Methods of using these compounds for modulation of Notch (Drosophila) homolog 4 expression and for treatment of diseases associated with expression of Notch (Drosophila) homolog 4 are provided.

Antisense modulation of G protein-coupled receptor 12 expression

Antisense compounds, compositions and methods are provided for modulating the expression of G protein-coupled receptor 12. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding G protein-coupled receptor 12. Methods of using these compounds for modulation of G protein-coupled receptor 12 expression and for treatment of diseases associated with expression of G protein-coupled receptor 12 are provided.